V ol.:(0123456789)
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Clinical and T ranslational Imaging (2019) 7:65–81
https://doi.org/10.1007/s40336-019-00314-7
SY STEMA TIC REVIEW
Evidenc e ‑based indications f ortheplanning ofPE T orPET/C T
capacities are needed
SabineF uchs 1 · NicoleGrössmann 2 · ManfredF erch 3 · ReinhardBusse 1 · Claudia W ild 2
Received: 29 December 2018 / A ccepted: 11 January 2019 / Published online: 20 F ebruar y 2019
© The Author(s) 2019
Abstr ac t
Purpose T o identify e vidence-based indications f or PET/PET–CT scans in suppor t of f acilities planning and to descr ibe a
pilot project in whic h this inf or mation w as applied f or an in vestment decision in an A ustrian region. The study updates a
Health T echnology Assessment (HT A) report (2015) on oncological indications, extending it to neurological indications
and inflammator y disorders.
Methods A systematic literatur e search to identify HT A repor ts, evidence-based guidelines, and sys tematic re view s/meta-
anal yses (SR/MA) w as per f or med, supplemented b y a manual searc h f or prof essional society recommendations and e xplicit
“not-to-do ’ s”. A needs-assessment w as conducted in the context of the pilot study on in v esting in an additional PET–CT
scanner in the Austrian region of Car inthia.
Results Ov erall recommendations f or indications as well as non-recommendations f or the t hree areas (oncology , neurol -
ogy , and inflammatory disorders) were compiled fr om the 2015 PET–HT A repor t and expanded f or a final total of ten HT A,
comprising 234 (positive and neg ative) r ecommendations from prof essional societies and databases, and supplemented by
findings from 23 SR/MA. For the in ves tment decision pilot study in Carinthia, 1762 PET scans were anal yzed; 77.8% w ere
assigned to the categor y “recommended evidence-based indications” (54.7%), “no t recommended” (1.8%) or “contradictor y
recommendations” (21.3%). The remaining could not be assigned t o any of the three categories.
Conclusions The pilo ting of PET capacity planning using evidence-based inf or mation is a first of its kind in the published
literature. On one hand, the high number of PET scans that could not be ascr ibed to an y of the categor ies identified limits to
the instr uctiv e pow er of t he study to use e vidence-based indication lists as the basis f or a needs-assessment in ves tment plan -
ning. On the other hand, this study rev eals how there is a need to impr ov e indication coding f or enhanced capacity planning
of medical ser vices. Ov erall recommendations identified can ser v e as needs-based and evidence-based decision support f or
PET/PET–CT ser vice pro vision.
Keywords Evidence-based planning· N eeds-based planning· PET/PET–CT· Oncology· Neur ology· Inflammator y
disorders· A dvanced diagnos tics
Introduction
Europe is one of the larg est mark ets f or the fas t-g ro wing
sector of medical de vices (MDs) and diagnostic procedures,
which encom pass a broad and heterog eneous rang e of tech -
nologies. Due to the r ising costs associated with introduc -
ing of ne w MDs and procedures into the healthcare system,
pa y ers ha v e star ted to pa y more attention to the effectiveness
and financial implications of suc h new tec hnologies. In this
conte xt, health technology assessment (HT A) has g ained
increasing recognition at the European le v el as a decision
suppor t tool [ 1 ].
Electronic supplementar y material The online v ersion of this
ar ticle ( https ://doi.org/10.1007/s4033 6-019-00314 -7 ) contains
supplementar y mater ial, which is a vailable to author ized users.
* Sabine Fuchs
sabine.fuchs@tu-ber lin.de
1 Depar tment ofHealth Care Manag ement, Berlin Univ ersity
ofT echnology (TUB), S traße des 17. Juni 135, H 80,
10623Berlin, Ger many
2 Ludwig Boltzmann Ins titute f orHealt h T echnology
Assessment (LBI-HT A), Vienna, A ustria
3 Carint hian State Hospital Operating Company (KABEG),
V ienna, Austria

66 Clinical and T ranslational Imaging (2019) 7:65–81
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No o ther medical technology has been e valuated as fre -
quentl y by HT A institutions in European countr ies as “posi -
tron emission tomograph y (PET)”, or rather “positron emis-
sion tomography/com puted tomog raph y (PET/PET–CT)” [ 2 ,
3 ]. In its 2015 assessment repor t [ 4 ] on PET/PET–CT , the
Ludwig Boltzmann Institute f or Health T echnology Assess -
ment (LBI-HT A) aimed to capture the e vidence base on
oncological indications f or a needs-based planning of PET/
PET–CT f acilities in Aus tr ia. It identified around 160 assess -
ments on PET or PET–CT in a 10-y ear per iod (2004–2014),
of which the first HT A were already published in 1995. This
e xpresses uncer t ainty about the value of PET diagnostics
in patient care. No tably , despite ongoing and controv er -
sial discussions about the patient-relev ant benefits of PET/
PET–CT , these technologies ha v e rapidly been adopted bo th
in Europe and abroad [ 2 ]. Additionall y , the majority of t hose
assessments is not accompanied b y decisions regarding the
reimbursement or planning of PET/PET–CT indications or
de vices. How ev er , se ver al approaches e xist to deal with (to
v ar ying deg rees) uncer t ain e vidence or contradictor y recom -
mendations around reimbursement and capacity planning
in Europe and globall y [ 4 ]. In practice, capacity planning
emplo ys a mix of different me thods and methodological
approac hes such as comparativ e approaches (e.g., benc h -
marking), anal ytical (e.g., health care needs-assessment)
and/or reactiv e approac hes (e.g., w aiting lists). T o provide
v olume f orecasts f or f acility planning and w orkload vis-à-
vis PET/PET–CT , the number of patients with (sub-)indi -
cations is impor tant as is t he estimated number of patients
eligible f or t herapy monitoring and radiotherapy dose plan -
ning. In addition, some special f eatures of PET/PET–CT
(e.g., required r adionuclides/tracers) ha v e to be taken into
account. Y et the planning of capacities based on evidence-
based indications is rarel y seen—neither in t he literature
nor in practice.
On the initiativ e of t he Ger man Society f or Nuclear Medi -
cine (DGN), the LBI-HT A and the Depar tment of Healt h
Care Manag ement at t he Berlin U niv ersity of T echnology
collaborated to (1) update the LBI-HT A 2015 repor t to iden -
tify indications recommended b y evidence [HT A, systematic
re view s/meta-analy ses (SR/MA), evidence-based guidelines
(EBG)] f or PET/PET–CT scans suppor ting f acility planning
in Ger man y and Aus tr ia and (2) descr ibe a pilot study whic h
applied those recommendations identified in the evidence
re view fr om step (1) to an in vestment decision in the A us -
tr ian region of Car inthia. The subsequent, updated, HT A
repor t e xtended t he scope of the 2015 repor t by including
indications f or neurology and inflammator y disorders in
addition to oncological indications.
The f ollowing article summar izes both the results of the
updated PET–HT A report, which has already been published
(in Ger man [ 5 ]), and the pilot study in A ustr ia testing the
practicalities of the recommendations.
Materials andmethods
(1) Evidenc e ‑based indic ations
andrecommenda tions
Sources ofinf ormation, search stra tegy , andstudy selec tion
A sys tematic literature searc h w as car ried out in July 2017
to identify HT A reports, SR/MA, and EBG to be included
in the study . The databases MEDLINE, EMB ASE, Pub -
Med, and Cochr ane Librar y were searc hed using a searc h
strategy re tr iev ed from a published repor t by the Ger -
man Institute f or Quality and Efficiency in Health Care
(IQWiG), whic h w as then updated and adapted [ 6 ]. A
5-y ear windo w (2012–2017) f or EBG and SR/MA w as
chosen [ 7 ]. HT A f or the new l y included indications (neu -
rology and inflammatory disorders) were limited to the
last 10 y ears (2007–2017), while the most recent HT A
[ 8 – 10 ] included in the PET–HT A repor t [ 4 ] wer e used
f or oncological indications, t hough oncological guidelines
already included in the PET–HT A w ere updated if new er
ones w ere a v ailable. Details about t he searches ar e f ound
in the Appendix A of t he repor t [ 5 ] and a translated v er -
sion is f ound in t he Online Resource 1 of this article.
The literature w as screened in a two-s tage process
(First: title/abs tract; second: full text) b y tw o researc h -
ers of the author g roup. Inclusion and e xclusion criter ia
w ere deter mined based on the cr iter ia from the PET–HT A
repor t 2015 [ 4 ] f or consistency . English- and German-
language HT A, SR/MA, and EBG on the benefits of PET/
PET–CT w ere included, if they discussed (1) patient-rele -
v ant benefits; (2) diagnostic accuracy/quality or c hange in
patient management; (3) if the y f ocused on one of the three
indications/treatment areas (oncological and neurological
indications, or inflammator y diseases); (4) w ere dev eloped
with an evidence-based me thodology (e.g., a descr iption
of a literature searc h ref erenced more t han tw o databases,
inclusion/e x clusion cr iter ia and quality assessment, and
double-chec k pr inciple); and (5) were freel y a vailable.
Differences in the assessment of literature w ere resol v ed
through discussion and consensus building. A detailed
o v er view of the cr iter ia f or inclusion and e x clusion can
be f ound in t he Online Resource 2 of this article.
In addition to the systematic searc h, a supplementar y ,
comprehensiv e manual searc h f or evidence-based r ecom -
mendations on the use of PET/PET–CT w as conducted.
The selection of databases or websites [e.g., Cancer Care
Ontar io (CCO) and National Com prehensiv e Cancer Net -
w ork (NCCN)] w as based on the PET–HT A repor t 2015
[ 4 ] and complemented b y rele vant sources f or the two ne w
indications. The searc h could not be car r ied out in a sys -
tematic manner due to v ar iation in search interf aces, but
the search term PET w as a common f actor . Up-to-date

67 Clinical and T ranslational Imaging (2019) 7:65–81
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recommendations of the f ollo wing national and suprana -
tional societies of nuclear medicine w ere included: Aus -
tr ian Society of N uclear Medicine and Molecular Imag -
ing (ÖGN), Ger man Society f or Nuclear Medicine (DGN),
Swiss Society f or Nuclear Medicine (SGNM), European
Association of Nuclear Medicine (EANM), Socie ty of
Nuclear Medicine and Molecular Imaging (SNMMI), and
Joint Collaboration of EANM and SNMMI. Databases
(e.g., Choosing Wisel y , NICE Do-not-Do database) that
e xplicitly identify “inappr opr iate” (not-to-do) ser vices
w ere also included as a source of inf or mation. Screening
of documents from w ebsites or prof essional societies w as
car r ied out by one person, with the extraction perf or med
using the double-chec k principle. Dur ing the process of
updating the HT A repor t, inf or mation sources wer e again
scanned betw een Januar y and Febr uar y 2018.
Data extraction
Extraction tables were compiled separ ately f or the t hree indi -
cations, using the double-chec k pr inciple. In a first summary
table, study char acter istics wer e extracted separatel y , because
they differ among HT A (e.g., repor ted endpoints and number
of included studies), SR/MA (e.g., ref erence standard), and
EBG (e.g., funding/sponsor ing and strength of the evidence).
Evidence der iv ed from HT A and SR/MA w as t hus presented
in the fur t her tables including t he evidence base and v erba-
tim conclusions. The recommendations from EBG and w eb -
sites and databases of national and supranational societies
w ere first e xtracted in tabular form and assessed along tw o
dimensions: (1) appropriate use cr iter ia and (2) inappropriate
use cr iter ia (e.g., suspension of decisions, recommendations
based on insufficient e vidence, and disin v estment recom -
mendations), including also the cor responding strength of
the evidence. R ecommendations of a cer t ain le vel/s trength
of e vidence (see Box 1 ) w ere then considered and clustered
according to type and content of recommendations f or fur t her
anal ysis into their similarities and differences.
Bo x1: included professional societies
anddatabases andthelev el/ strength ofevidence
taken in toacc ount fortherec ommendations
e vidence hierarch y dev eloped b y the AANS/CNS
Guidelines Committee (but no recommendation due
to insufficient e vidence)
• Amer ican College of Radiology (A CR): A CR Appro -
pr iateness Cr iter ia ® : 7–9 = appropriate indications
(4–6 = ma y be appropriate indications w as not consid -
ered f or t he table, are a vailable on request) *
• Br itish Society f or Hematology (BSH): GRADE w as
used to e valuate LoE and to assess the str ength of rec -
ommendation (onl y A and B recommendations wer e
considered)
• Canadian Association of Radiologists (C AR) Ref er ral
Guidelines: GRADE 1 = indicated, (“2 = Specialized
In vestig ation” w as not considered f or this t able, a v ail -
able on reques t) * & based on A (high-quality diag -
nostic studies suc h as studies in which a ne w test is
independentl y and blindly com pared with a ref erence
standard in an appropriate spectr um of patients, etc.),
B (lo wer case e vidence in which the ref erence standard
does not appear on all subjects, e tc.), or C (studies in
which the ref erence standard w as not objectiv e, expert
opinion, etc.) w ere considered
• Cancer Care Ontar io (CCO): LoE/GoR not indicated
(onl y literature assigned to the recommendations)
• European Association of N uclear Medicine (EANM)/
Society of N uclear Medicine and Molecular Imaging
(SNMMI): onl y Grade A and B considered
• European Federation of N eurological Societies
(EFNS): good practice points not considered (lac k of
e vidence but consensus by e xper t reac hed) and only
recommendations f or PET t aken
• Ger man Society f or Nuclear Medicine (DGN): LoE/
GoR not indicated (onl y literature assigned to the rec -
ommendations)
• Inter national my eloma W orking Group (IMW G): LoE/
GoR according to OECBM (onl y A = Evidence of type
I or consistent findings from multiple studies of types
II, III, or IV and B = Evidence of II, III, or IV , findings
are g enerally consis tent) were consider ed
• Response Assessment in N euro-oncology w orking
group/European Association f or Neuro-Oncology
(RANO/EAN O): only 1–3 LoE according t o OCEBM
included in their study (no inf or mation of LoE f or t he
recommendations separatel y)
• R o yal Colleg e of Radiologists and R oy al College of
Ph ysicians (R CR/RCP): no LoE/GoR indicated (onl y
literature assigned to the recommendations)
• R yken et al.: e vidence hierarch y dev eloped b y t he
AANS/CNS Guidelines Committee (le vel III = Clini -
cal uncer tainty (inconclusive or conflicting e vidence
or opinion)
Le vel and s trength of e vidence considered f or appro -
priate use:
• Amer ican College of Ches t Phy sicians (A CCP): o wn
grading system (onl y 1B recommendation a vailable;
grade 1B = strong recommendation, moderate q uality
e vidence)
• Amer ican Association of Neurological Sur geons
(AANS)/Congress of Neurological Sur geons (CNS):

68 Clinical and T ranslational Imaging (2019) 7:65–81
1 3
• SNMMI/Alzheimer ’ s Association (AA): no LoE/GoR
indicated (onl y literature assigned to the recommenda -
tions)
• SNMMI + EANM and Amer ican College of N uclear
Medicine (A CNM), American College of Pre v entiv e
Medicine (A CPM), Amer ican Society of Clinical
Oncology (ASCO), Canadian Association of N uclear
Medicine (CANM), and Socie ty f or Pediatric Radiol -
ogy (SPR): 7–9 = appropriate indications (4–6 = ma y
be appropriate indications which w ere not considered
f or t his table, a vailable on req uest)
• N ational Comprehensiv e Cancer Netw ork (NCCN):
onl y LoE categor y 2A w as considered (= based on
lo wer le vel e vidence, there is unif or m NCCN consen -
sus that the inter v ention is appropriate; LoE 2B a vail -
able on reques t; LoE 1 w as not indicated f or any of the
recommendation) * & onl y ‘pref er red’ recommenda -
tions w ere considered
Le vel and s trength of e vidence considered f or inap -
propriate use:
• A CR: 1–3 = not appropr iate (4–6 = ma y be appropr i -
ate indications w as not considered f or the t able, are
a vailable on req uest) *
• Choosing Wisel y US A (ChW) and NICE Do-not-Do
database: respective r ecommendations (both wit hout
“ratings”) w ere ev aluated
• CAR: GRADE 5 = not indicated (GRADE 3 = not indi -
cated initiall y , 4 = indicated onl y in specific circum -
stances wer e not considered f or t his t able, a vailable on
reques t) based on A, B, and C LoE (see abo v e) *
• European Crohn ’ s and Colitis Or ganization/European
Society of Gastr ointestinal and Abdominal Radiology
(ECCO/ESG AR): OECBM LoE 1–3 considered
• NCCN guidelines pro vide no separate categor y f or
inappropriate use; all guidelines were searc hed manu -
all y f or inf or mation on inappropriate use/insufficient
e vidence
• BSH, CCO, CNS/AANS, EANM/SNMMI, EFNS,
IMW G, RANO/EANO, R CR/R CP , R yken, and
SNMMI/AA: see inf or mation abo v e on appropr iate use
LoE le vel of evidence, GoR grade of recommendation
* Mainl y due to the larg e amount, only those recom -
mendation from A CR, CAR, and NCCN with a cer -
tain lev el of recommendation w ere taken into account
T able 1 Colour coding of recommendations and le v el of contradictions betw een the evidence sources f or the ov erall recommendations t able
Classificaon of

recommendaons
"Yes" (indicaon to use, PET/PET-C Ta s primary treatment)

"No" (no indicaon to use, insufficient/inconclusive evidence)
"Restricted Use" (only as second-line or connuave method within an indicaon)
"Unclear" (no concrete or contradictory recommendaons)
Level of
contradicons
between the
evidence sources
Consensus of
sufficient
evidence in
favour of
PET/PET-CT
Consensus of
not sufficient
evidence in
favour for
(against)
PET/PET-CT

Divergent
statements
(HTA vs. EBG vs.
SR/MA) or
contradictory
results

Divergent
statements
between EBG
or
contradictory
results

Recommendaon
derived only from
one source (HTA
or EBG)
Synthesis ofr ecommendations
A summar y of the recommendations der iv ed from each of
the t hree source types (HT A, EBG, SR/MA) w as str uctured
according to their indication. These are presented belo w .
Based on the PET–HT A repor t 2015 [ 4 ], a classification
of the recommendations into the categor ies “Y es”, “N o”,
“Res tr icted Use”, and “Unclear” w as applied (T able 1 ). A
color sys tem show s the lev el of contradictories between the
e vidence sources (HT A, EBG, and SR/MA) regar ding t he
respectiv e recommendations and the strength of evidence.
For oncological indications, recommendations from the
PET–HT A report 2015 are included as well.
Quality assessment
The quality of the included inf or mation sources was
appraised b y appropr iate and v alidated tools, depending on
the respectiv e sources. The quality of HT A was assessed via
a double-chec k approach supported by a c hec klist from the
Inter national Ne twor k of Ag encies f or Health T echnology
Assessment (IN AHT A [ 11 ]) of 14 ques tions answered with
“y es”, “par tly”, and “no” (no to t al score). The A GREE II
instrument (Ger man v ersion [ 12 ]) w as used to assess the
quality of EBG. Eac h guideline w as ev aluated by three inde -
pendent re vie wers acr oss six domains and a total of 23 items
on a se ven-point scale. It w as determined t hat revie wers
w ould de viate a maximum of tw o points in t heir final e valu -
ations. In the ev ent of a discrepancy of more than two points
per item, the questions w ere discussed and a consensus was

69 Clinical and T ranslational Imaging (2019) 7:65–81
1 3
reac hed. The EBG were finall y re-ev aluated in t heir entirety
resulting in an a verag e score f or each guideline. The SR/
MA w ere assessed by tw o revie wers independentl y with
AMS T AR -2 [ 13 ], compr ising a questionnair e consisting of
16 y es/no ques tions. Discrepancies w ere resol v ed b y consen -
sus. Ov erall quality w as deter mined pr imar ily b y consider -
ing the cr itical questions (defined b y t he dev elopers of t he
instrument [ 13 ]) and by allocating eac h SR/MA into one of
f our suggested ca tegor ies (high, moderate, lo w , and critically
lo w) [ 13 ]. For more details on the methods used, see t he full
repor t and the cor responding Appendix C [ 5 ].
(2) Pilot study: evidenc e ‑based PET/PE T –C T
planning
A study w as car r ied out to guide the in ves tment decision f or
an additional PET–CT scanner in the region of Car inthia
in Aus tr ia (561,000 inhabit ants). First, a needs-assessment
based on a data analy sis of PET scans w as conducted. Diag -
noses w ere coded according to the Inter national Statistical
Classification of Diseases and Related Health Problems
10 th re vision (ICD-10, 2016 [ 14 ]). All PET scans per -
f or med from January to September 2017 were re tr iev ed
and clustered according to disease diagnosis (e.g., tumour
type: C.00; malignant neoplasm of lip) and, if a vailable, to
subgroups of indications (e.g., C00.1 e xter nal low er lip).
The inf or mation w as t hen matched to identify recommenda -
tions f or evidence-based indications or non-indications [see
step (1)]. Indications with contradictor y recommendations
w ere—due to lack of de tailed clinical inf or mation—ascr ibed
to the categor y of dissenting or unclear evidence from HT A
and/or guidelines. The categor ization as well as the matc h -
ing with evidence-based indications w as per f or med by tw o
researc hers.
Records identified through database searching
(n =1 0.873) , no time limit
MEDLINE (n= 5.975), Embase (n= 3.465)
PubMed (n= 858), Cochrane Library (n= 539)
Screening
Included Eligibility Idenficaon
Additional records identified
through other sources
(

n= 27
)

Duplicates removed
(n =2 .729)
Records screened*
(n =8 .144)
Records screened (Title/Abstract) (n =3 .845)
Records excluded
(n =3 .412)
Full-text articles assessed for eligibility
(n =4 33)
HTA (n =3 2), EB G( n= 31)
SR/MA (n= 370)
Full-text articles excluded,
with reasons (n =3 90)* *
HTA: HTA not (freely) available/ not
found (n =1 1), language (n =9 ), no
PET/PET-CT Fokus (n =2 )
EBG: No EbM method used (n =1 1),
broad spectrum (n =2 ),
no PET/PET-CT focus (n =1 ), indication
(n =1 ), further (n =3 )
SR/MA: Country (n= 146),
no EbM method used (n =9 8), study
type (n =6 4), no PET/PE T- CT focus (n=
20), research question (n= 8), further
(n =1 4)
Studies included in qualitative synthesis
(n =4 3)
Overall: HTA (n= 10), EBG (n= 13),
SR/MA (n= 20),
+ Update :H TA (n= 0), EBG (n= 1),
SR
/

MA
(

n= 3
)

Records excluded
(n =4 .299)
HTA u. SR/MA < 2007 (n= 1.742),
EB G< 2012 (n= 2.557)
Fig . 1 PRISMA flo w chart : study selection process of the sys tematic search [ 5 ]. *Due to the lar ge amount of records identified, a time limit w as
set up f or t he title/abstract screening of SR/MA. **Online Appendix D [ 5 ] contains a list of e x cluded ar ticles with reasons

70 Clinical and T ranslational Imaging (2019) 7:65–81
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Results
(1) Evidenc e ‑based indic ations
andrecommenda tions
Results oftheevidence selection process
The sys tematic search yielded 10,873 ref erences (Fig. 1 ).
After t he remo val of duplicates (2729 r ef erences) and the—
e x post—introduction of a time limit (due to an enormous
amount of mater ials), 4299 ref erences w ere ultimately
e x cluded and 3845 ref erences remained f or t he tw o-step
screening. Of these, 3412 ref erences were e x cluded accord-
ing to the inclusion and ex clusion cr iter ia, lea ving 433 full
te xts, 43 of which w ere finall y included (10 HT A repor ts, 20
SR/MA, and 13 EBG). An o v er view of the e x cluded ref er -
ences ( n = 390) with reasons can be f ound in the Appendix
D of the updated HT A repor t [ 5 ]. The screening of the col-
lected aler ts of the dat abase searches (update: from Jul y to
December 2017) resulted in three more HT A, one EBG, and
three SR/MA. As such, a t otal of 47 ref erences w ere included.
The updated searc h results in guideline databases and
w ebsites and databases of relev ant national and suprana -
tional societies reg arding recommendations (see tables in
repor t [ 5 ]) w as compared with the results of the sys tem -
atic researc h and the PET–HT A Repor t 2015, resulting in
additional “appropriate use” recommendations from sev en
prof essional societies: DGN and the joint collaboration
betw een EANM and SNMMI, R CP/R CR, A CR Appro -
pr iateness Criter ia ® , CAR R ef er ral Guidelines, and tw o
oncology e xper t netw orks f or guideline de v elopment, CCO
and NCCN . It also resulted in concrete “not-to-use” recom -
mendations from f our societies or databases: ACR, C AR,
and the tw o disin v estment databases Choosing Wisel y and
NICE Do-not-Do database. Thus, a total of ten HT A, and
234 positiv e and negativ e recommendations from prof es -
sional societies and databases wer e included, supplemented
b y the statements from 23 SR/MA.
Evidenc e ononcological indications
Study characteristics
The PET–HT A report (2015) included 35 HT A assessments
on 20 oncological indications. In addition, the repor t update
re v ealed two no vel HT A on bronchial carcinoma fr om the
US Ag ency f or Healt hcare Researc h and Quality (AHRQ)
[ 15 ] and the HT A-Center f or the V ästra Gö t aland Region,
Sw eden [ 16 ] as well as one HT A each on mamma carci -
noma, compiled also b y AHRQ [ 15 ], on penile/testicular
carcinoma and on bladder/renal cancer , t he latter tw o com -
piled b y the Scottish Health T echnologies Gr oup within
Healthcare Impro v ement Scotland (SHTG/HIS [ 17 – 20 ]). F or
fur ther oncological indications considered in t he PET–HT A
repor t 2015, no more recent HT A w as f ound. Reported end -
points in the included studies used f or t he HT A repor ts ref er
to diagnostic accuracy (mainl y tumour g rading and chang e
in management).
Recommendations as w ell as non-recommendations
( n = 188) from p rof essional societies (see Bo x 1 f or abbre via -
tions) w ere retriev ed and e xtracted from AANS/CNS [ 21 ],
A CCP [ 22 ], BSH [ 23 ], CCO [ 24 – 26 ], DGN [ 27 ], IMW G
[ 28 ], and RCR/R CP [ 29 ]. Three common guidelines, one from
SNMMI/EANM and others (A CNM, A CPM, ASCO, C ANM,
and SPR) [ 30 ], one fr om RANO/EANO [ 31 ], and one from
EANM/SNMMI [ 32 ], w ere also considered. One guideline
(R yken et al. [ 33 ]) has been elaborated b y se ver al unive rsities.
Three guidelines (CCO [ 24 ], R CR/RCP [ 29 ], SNMMI/
EANM/others [ 30 ]) pro vided recommendations f or tumours
gener ally as w ell as f or non-oncological indications. Another
three guidelines dealt with tumours of t he head (DGN [ 27 ],
R yken [ 33 ], RANO/EAN O [ 31 ]); tw o f ocused on my eloma
(BSH [ 23 ], IMW G [ 28 ]); and one guideline addressed pros -
tate cancer (EANM/SNMMI [ 32 ]), anal canal carcinoma
(CCO [ 25 ]), lung carcinoma (A CCP [ 22 ]), paraneoplas -
tic syndrome (PNS) (CCO [ 26 ]), and pituitary adenoma
(AANS/CNS [ 21 ]), respectiv el y . The recommendations of
A CR [ 34 ], CAR [ 35 ] and N CCN [ 36 ] as well as the e xplicit
non-recommendations of c hoosing Wisel y [ 37 ] and NICE
Do-not-Do [ 38 ] w ere also considered.
Moreo v er , 12 SR/MA f or sev en oncological sub-indica -
tions w ere included [ 39 – 50 ]; of those, two supplemented an
HT A report [ 49 , 50 ] and all considered diagnos tic accuracy
as an endpoint, especiall y f or pr imar y diagnosis and stag -
ing f or pre-treatment/treatment planning. The systematic
re view s consisted pr imar ily of r etrospectiv e studies.
Quality assessment
The quality of the HT A w as ov erall very good, with only
a f ew q uestions not e v aluated with “yes”. The assessment
of the quality of the guidelines v ar ied. In domain 1: “scope
and pur pose” and domain 4: “clar ity of present ation”, the
guidelines receiv ed high ratings and there were f e wer v ar ia -
tions among the guidelines. Domain 3 (“r igour of dev elop -
ment”), which considers the accuracy of guideline de velop -
ment, rang ed from 11% (DGN [ 27 ]) to 93% (A CCP [ 22 ]),
sho wing the larg est differences among the guidelines. In the
o v erall rating, the ACCP guideline [ 22 ] w as giv en a score of
5.67 (max. 7) and also ranked highes t among tw o domains 3
and 4. The R CR/R CP guideline [ 29 ] attained last place with
a mean score of 2.67.
The quality of the SR/MA in terms of ov erall qualitative
assessment (no o v erall score) re vealed that 10 out of 12 w ere
“cr iticall y low”. Hence, the SR/MA is used onl y as supple -
mentar y inf or mation.

71 Clinical and T ranslational Imaging (2019) 7:65–81
1 3
T able 2 PET/PET–CT indications (oncology): o v erall recommendations
RU (2) b,d D/S pulmonary & thoracic nodule (specific cases described by ACR, CAR)
No (3) b,e,o D/S pulmonary nodule (specific cases described by ACR)
TM (roune surveillance + follow - up) SCLC/NSCLC
TP (roune use outside research seng) SCLC/NSCLC
Unclear
(4) a,e,n,o
Contradictory recommendaon:
R/R SCLC/NSCLC: Yes (SNMMI/ACCP) vs. insufficient evidence (CCO)
TM (response evaluaon) SClC: Yes (SNMMI) vs. No (NCCN)
EsophagealCa
No* No recommendaon due to insufficient
evidence
RU* Just as connuave diagnoscs, contradictory
Yes (2) e,l Re -/Staging before therapy/treatmen
tT

M (treatment response):
pot. useful
Unclear
(3) e,l, o
Contradictory recommendaon:
R/R (suspected recurrence): RU (RCR/RCP) vs. insufficient evidence (CCO)
TM (treatment response): Yes (NCCN) vs. insufficient evidence (CCO)
GastricCa
No* Scarce evidence No* No appropriate use criteria
No HTA/GL/SR/MA idenfied (Update)
PancreacCa
RU* Inconclusive evidence, pot.diagnosis RU* Contradictory recommendaon
No (2) d,e Primary diagnosis
R/R (re -s taging), TP (treatment response), TM (guide clinical management) pancreac
adenocarcinoma insufficient evidence
Unclear
(3) d,e,l
Contradictory recommendaon:
Staging before curave surgical resecon: Ye s( CAR, CCO) vs. RU (RCR/RCP)
LiverCa
No* Weak (scarce) evidence No* No appropriate use criteria
Yes (1) l 11 C- Choline,
18 F- fluor o- choline, G a- PSMA, 11 C- Acetate: TP HCC
RU (2) d,l D/S, R/R hepato -( pancreaco )- billaryCa
D/S liver lesion
No (2) b,o D/S (primary diagnosis) HCC
D/S liver lesion (specific cases described by ACR)
TP (roune use pre - operave) –
–
insufficient evidence
AnalcanalCa
No (1) e D/S (roune invesgaon), R/R & TM analcanalCa –
–
insufficient evidence
•
–
HT A( n) Notes EBG (n) Notes Addional informaon from SR/MA
Brain Tumor
No* No recommendaon, weak evidence RU* Contradictory recommendaon (glioma)
RU (2) h,l D/S (grading tumor, disng. WHO grades, differenal diagn. of tumor/glioma) Primary diagnosis (brain tumor,
glioma): 18 FE T- PET higher
diagnosc performance than FDG
PET (Grading: no difference
between tracer)
RU (3) h,k,l Amino Acid: D/S (grading tumor), R/R + TM
No (4) b,e,k,m D/S & TP (glioma)
Roune use (brain metastases & glioblastoma)
Follow - up (specific case described by ACR)
R/R + TM (glioma) -i nsufficient evidence
Unclear (2) k,l Contradictory recommendaon:
TP (glioma): RU (RCP/RCR) vs. RU (RANO/EANO: not grade III/IV glioma)
Head and NeckCa
RU* Some evidence, Re -/Staging + Thyroid RU* CUP, Thyroid, contradictory for other Ca
RU (5) b,d,e,l,n D/S (+ CUP), R/R (local recurrence, metastases) + TP head and neckCa
TM (response evaluaon) Head and NeckCa
R/R (suspected recurrence) thyroid
R/R (residual disease) parodCa (problem solving tool)
11 C- Menthione: D/S (localizaon) parathyroidCa (difficult cases)
No (2) b,d D/S head and neckCa (specific cases describe db y ACR)
Staging (I or IIA/B) thyroidCa
MammaCa
No* Inconclusive evidence No* No appropriate use criteria, pot. diagnosc of recurrence
Yes (1) 18 F -F ET:
MammaCa (mainly bone metastases)
Yes (2) l,n TM (treatment response) bone metastases D/S: Beer diagnosc
performance for distant
metastasis staging of whole -b ody
18 F-
FD G - PET/PET -C T compared to
convenonal imagining
Yes (3) b,l,n R/R (suspicion of metastac disease, local recurrence) known
breast cancer/dense breast
No (5) b,e,f,o,p D/S (specific cases decribed by ACR, e.g. high risk paents)
D/S (staging)
TM (monitor) advanced breast cancer
BronchialCa – Update: Thorax/LungCa
RU* Some evidence Re - /Staging RU* Different su b- indicaons, less contradictory
Yes (1) 18 F -F DG: Pre -treatment staging
of SCLC
Yes (4) b,d,e,l 18 F -F DG: Pre - treatment staging SCLC/NSCLC (curave intent), thymic tumor, pleural
malignancy
Yes (1) 18 F -F DG: TP (prior to dose planning)
SCLC/NSCLC
•
•
TM (tumor response) metastac

72 Clinical and T ranslational Imaging (2019) 7:65–81
1 3
T able 2 (continued)
HT A( n) Notes EBG (n) Notes Addional informaon from SR/MA
ColorectalCa
RU* Some evidence Staging/Recurrence RU* Remote metastases/Re -s taging/Therapy monitorin g
less contradictory
RU (4) d,e,l,n D/S (staging) only in selected cases (problem solving tool)
Less contradictory
R/R (re -s taging (recurrence)), TP (therapy planning, monitoring)
Highly accurate for detecon of
liver metastases in PT with
Colore ct alCa, more specific than
PET/MRI
Affects changes in
PT management
No (4) d,e,f,o D/S (roune use)
TM (roune surveillance)
BladderCa
No* Scarce/inconclusive evidence No* No appropriate use criteria
No (1) Scarce evidence (D/S, R/R) No (3) b,d,o D/S bladder/urothelialCa + TM superficial TCC
Yes (1) l TP (curave intent) advanced muscl e- invasive bladderCa
RenalCa
No* Scarce evidence No* No appropriate use criteria
Unclear
(1)
R/R (disease recurrence or metastases)
insufficient evidence
RU (1) l D/S (staging) (metastac) renal (ureteric)Ca
UtericCa
No* Scarce evidence No* No appropriate use criteria
Yes (2) d,l Re -/ staging utericCa (radical intent)
RU (2) b,d R/R (recurrence) endometrialCa
CervicalCa
RU* Some evidence Staging/Recurrence No* No appropriate use criteria, pot. for locally advanced Ca
Yes (2) d,l Re -/ staging (radical chemotherapy) locally advanced cervicalCa
TP (pelvic e xenteraon/chemoradiaon, curave intent)
RU (2) b,l R/R (recurrence) cervicalCa
TM (aer chemoradiotherapy) locally advancedCa
No (2) b,e TM (follo w- up) specific cases described by ACR, aer chemotherapy
Unclear (1) e ) g n i g a t s ( S / Di nsufficient evidence
OvarialCa
No* Scarce/inconclusive evidence No* No appropriate use criteria
Yes (1) b R(R (recurrence) loc o- regional and distant disease
RU (1) l D/S (detecon of tumor) rising CA125 level
−
No (2)
b, e
D/ S (d ia gn osis )
D/ S (s ta gi ng ), spe ci fic c as es ( hi gh r is k) des cribed by AC R
R(R (recurrenc e, r e- st aging) n ot c on si de red for su rg er y
TP (PT con si de re d fo r seco nd ary cy toreduc on ) –i nsu ffic ie nt e vi denc e
Tescu larC a
No * Inco nc lu si ve e vi denc e No * No a pp ro pr ia te use c ri te ri a
No (1) D/ S (s ta gi ng ), R /R ( re-sta gi ng ) –
in su ffic ie nt e vi denc e
RU (3)
d, e, l
D/ S (M sta gi ng )
R/R (rec ur renc e)
TM (treatmen t re sp on se ) semino ma
No (1)
e
R/R (r ou n e us e) – i nsu ffic ie nt e vide nc e
TM (treatmen t re sp on se ) no ns em in om a
Pros ta te Ca
No * No t in di cate d No * No a pp ro pr ia te use c ri te ri a
RU (2)
h, l 11
C- Chol ine,
18
F- flu or o- choline,
68
Ga -PSM A : Pre-treatment st ag in g
in h ig h-risk PT + re cu rr en ce
11
C- Chol ine,
68
Ga-P SM A: pre-
tr ea tm en t stag in g + re cu rr en ce
(GA- PS MA -f avor ab le )
18
F- FA CB : R/ R ( po t. t ool fo r
re cu rr en ce )
No (2)
b, f
D/ S, T M (specific c ases d es cr ib ed )
PenilC a
No * No t in di cate d No * No a pp ro pr ia te use c ri te ri a
Ye s (1 )
l
Pre-trea tm en t st aging
No (1) D/ S (s ta gi ng ) R/ R (r e- stag in g) P en il eC a –
in su ffic ie nt e vi denc e
Muscul osce le ta l an d so  s su e CA (+G IS T)
No * No final re comm enda on po ss ib le RU * Biol og ic al a gg re ss iv en es s befo re surge ry, GI ST
Ye s (2 )
l, n
D/ S (s ta gi ng ), T P (pre -a mp ut aon ) hi gh g ra de s arco ma
R/R (rec ur renc e) s ar coma
D/ S, T P (p re -t re at me nt s ta gi ng ), R /R (tr ea tm en t response) GI ST
RU (2)
b, l
D/ S, R/R m us cu lo skel etal t um or ( sp ecific c ases d es cr ib ed by ACR)
D/ S me ta sta c sarcoma suitable for m et as tase ct om y
18
F- flu or idebon e im agin g : D/ S be ni gn m al ig na nt b on e di se as e
No (1)
b
D/ S so  s sue ma ss es a nd m us cu lo skel et al t um or (sp ec ific ca se s de sc ri be d by A CR )
Un cl ear
(3 )
b,l, n
Cont ra di ct or yr ec ommend a on :
D/ S osteos ar coma : Ye s (RCR/RCP) vs. No
(spe ci fic c as e de sc ri bed by Ameri ca n Co ll eg e of Rad iolo gi st s)
TM (treatmen t re sp on se ): Yes, sa rc oma (S NMMI) vs .
Ye s, but onl y for hi gh g rad sarcoma RCR/RC P
•
•
•
•

73 Clinical and T ranslational Imaging (2019) 7:65–81
1 3
Overall r ecommendations
T able 2 pro vides an ov er vie w of t he o v erall recommenda -
tions on oncological indications (see also T able 1 f or the
e xplanation of colors and categor ies).
There is a (relativ e) consensus that there is sufficient
e vidence f or sub-indications in eight indications in f a v our
of PET or PET–CT e xaminations (in T able 2 highlighted
green). The first six w ere already determined in t he 2015
repor t—(1) bronchial car cinoma (update: mainly pre-
treatment, contradictory in re-staging and response con -
trol and in therapy monitoring), (2) colon carcinoma, (3)
malignant l ymphoma, (4) malignant melanoma (update:
contradictor y f or diagnosis of recur rence), (5) mamma car -
cinoma (treatment response, f or diagnosis of recur rence),
and (6) head–nec k tumours (in 2015 repor t: CUP , thyr oid
carcinoma; update: mainl y f or diagnosis of recur rence)—
while tw o ne w treatment areas were added b y t he update:
(7) m yeloma and (8) neuroendocr ine tumours.
There is a (relativ e) consensus that, in eight other indi -
cation areas, there w as too little evidence in f a v our of PET
e xamination (individual decisions possible) (in T able 2
highlighted red): (1) bladder carcinoma, (2) hepatic can -
cer , (3) cer vical carcinoma, (4) gas tr ic cancer, (5) o var -
ian and (6) uter us carcinoma, (7) prostate cancer , and (8)
paraneoplastic neurological syndrome.
T able 2 (continued)
Medi ca l in di ca  ons n ot r eported in LBI -H TA r ep or t
Al l tu mo rs
RU (2 )
d, l
D/ S (s pe c ific ca se s de sc ri be d) oligometastac diseas e + CU P
No (3 )
d,f, g
R/R, ro u ne su rvei ll an ce + sc re eni ng he althy in di vidu al s
TP aden om a
Myel om a
Ye s (3 )
c, j, l
D/ S, R/R, TM (s pe cific cases described)
No (2 )
b, l
D/ S (r ou n e us e) in su fficie nt ev id en ce
D/ S mu lpl e my el om a (s pec ific ca se de cr i bed )
Neur oe nd oc rine tumo r
Ye s (1 )
l
D/ S, R/ R (r e- st aging) , TP pa ra ga ng lioma
68
GA -D OTAT AT E PET mo re se ns .
& sp ec. th an
68
GA -DOT AT OC
Ye s (1 )
l 68
Ga -l abelled SS R : D/ S (s ta gi ng), R/ R (recurrence)
18
F-Fu or oD OP A: D/ S (s el ec te d pa e nt s)
RU (1 )
l
TP (pre-tre at ma nt) ad re no corcalC a
No (1 )
o
TM (surveilla nc e)
•
–
HT A( n) Notes EBG (n) Notes Addional informaon from SR/MA
Lymphoma
RU * So me ev id en ce
Interim-/R e- /S tagi ng /Rec urre nc e
RU * Di ffe rent sub- in di ca o ns
Ye s (4 )
d, e,l, o
D/ S e. g. ca st elma n’ s di se as e
TM (treatme nt re sp on se )
PET-ba se d tr ea tm en t a ssess me nt
sh ou ld be co ns id er ed in th e
manage me nt of PT with fo llic ul ar
ly mp ho ma (p ost-chem otherapy
resp on se as sess me nt )
RU (2 )
e, l
D/ S, TP HL/N HL
No (4 )
b, e, l, p
TM (m on it oring + su rv ei ll an ce ) ro u ne use HL /N HL
Un cl ear
(4 )
d, e, l, n
Cont ra di ct or yr ec ommend a on :
R/R (rec ur r ent di se ase) : RU (CCO , CA R) vs . Ye s (R CR/RCO , SNMMI)
Me la no ma
RU * Di ag no s c ac cu ra cy de pe nd in g on tu mor
gr ad e
RU * St aging/ Recu rre nc e in hi gh er st ages , less co nt radi ct or y
Ye s (4 )
d, e,l, n
D/ S (s ta ging ) high -r is k PT (a dv an ce d st ag es ) with po t. re se ctable dise as e
D/ S (s pe c ific ca se s de sc ri be d, e. g. me rk el -cel lC a)
R/R (rec ur renc e)
St aging: be e r diag no sc
a ccuracy in high -r is k PT
No (3 )
e, f, l
D/ S (r ou n e us e) pr im ary uv ea l ma li gn ant me la no ma
D/ S (s ta ging ) I, II a, II b mela no ma
D/ S (d ia gn osis ) sennel ly mp h no de mi crom etasta c dise as e
D/ S lo ca li se d pr im ar y cu ta ne ou s me la no m
TM (treatme nt re sp on se , roune surv ei ll an ce) –i ns uffici en t ev idence
Un cl ear (2 )
l, n
Cont ra di ct or yr ec ommend a on :
TM (treatme nt re sp on se ): Yes (SNM MI ) vs. RU (RCR /RCP )
Paraneo- pl as c synd ro m (P NS )
No * Sc ar ce ev id en ce No * No t de sc ri bed
RU (2 )
e, l
D/ S (s pe c ific ca se s de sc ri be d)
•
•
Ca carcinoma, D/S diagnostic/staging, 18 F -FDG fludeoxy glucose (18F), 68 Ga-PSMA 68 Ga-labelled prostate-specific membrane antig en, GoR
grade of recommendation, GIST gastrointes tinal stromal tumours, GL guidelines, H TA healt h technology assessments, LoE le v el of evidence,
MRI magnetic resonance imaging, NHL non-hodgkin-l ymphoma, NSCLC non-small cell lung cancer , PT patients, R/R recur rence/re-staging, RU
restricted use, SCLC small cell lung cancer, T CC transitional cell carcinoma, TM therapy monitoring, TP therapy planning
*Recommendations fr om PET–HT A repor t 2015 [ 4 ]; color coding of recommendations and lev el of contradictories between the e vidence
sources: see T able 1 ; the number of HT A repor ts/guidelines is given in brac kets; superscript letters indicate the respectiv e guideline: a. A CCP ,
b. A CR, c. BSH, d. CAR, e. CCO, f. ChW , g. CNS/AANS, h. DGN, i. EANM/SNMMI, j. IMW G, k. RANO/EAN O, l. RCP/R CR, m. R yken, n.
SNMMI, o. NCCN , p. NICE Do-not-Do; LoE/GoE f or appropriate use/inappropr iate use: see Box1; inf or mation giv en in the t able ref er to FDG
PET and PET–CT , and the use of other tracer are indicated in the t able

74 Clinical and T ranslational Imaging (2019) 7:65–81
1 3
For a fur ther set of eight indications, there is contradic -
tor y and equiv ocal evidence and recommendations w ere
de veloped along with reservations (in T able 2 highlighted
y ello w or blue): (1) anal canal, (2) brain (especially gli -
oma), (3) testicular , (4) renal, (5) penile carcinoma, (6)
esophagus cancer (e x cept re-staging), and (7) pancreatic
carcinoma as w ell as (8) bone and sof t-tissue tumour
(+ g astrointestinal s tromal tumour).
Evidenc e onneurological indications
Study characteristics
T w o HT A repor ts were identified about neurological indi -
cations f or t he use of PET—one from the Australian Medi -
cal Ser vices Advisory Committee (MS A C) [ 51 ] looking
into Alzheimer ’ s dementia (AD) and one compiled b y t he
Canadian Ag ency f or Dr ugs and T echnologies in Health
(CAD TH) on epilepsy [ 52 ]. Repor ted endpoints in the
included studies of these HT A reports ref er mainly t o diag -
nostic accuracy ; no study could be identified that in v esti -
gates diagnos tic effectiv eness and saf ety .
Recommendations and non-recommendations ( n = 28)
from prof essional societies (see Bo x 1 f or abbre viations)
w ere retriev ed and extracted f rom CCO [ 24 , 53 ], EFNS [ 54 ],
R CR/R CP [ 29 ], SNMMI/AA [ 55 ], and a common guide -
line from EANM/SNMMI [ 56 ]. R CR/RCP [ 29 ] pr ovides
recommendations f or sev eral non- and oncological indica -
tions. T w o fur ther guidelines ([ 54 , 55 ]) consider Alzheimer’ s
dementia/dementia (ADD) or AD onl y , while another guide -
line (EANM/SNMMI [ 56 ]) presents g eneral recommenda -
tions on brain-related disorders (ref er to SNMMI/AA [ 55 ])
CCO [ 24 , 53 ] (tw o guidelines) which considers epilepsy .
In total, three SR/MA were included (f or AD) [ 57 – 59 ]. All
consider diagnostic accuracy in terms of pr imar y diagnosis
as the endpoint. Pr imar ily , prospective s tudies were included
in the SR/MA.
Quality assessment
The quality of the HT A w as rated as v er y good, wit h onl y
one ques tion not judged as “y es”. The assessment of t he
quality of the guidelines sho wed that domains 1 (“scope
and pur pose”) and 4 (“clar ity of present ation”) receiv ed
v er y high ratings and are quite consis tent. How e v er , in
ter ms of editor ial independence, applicability , and accu -
racy of the guideline dev elopment, big differences were
obser v ed. In the ov erall assessment, SNMMI/AA [ 55 ]
ranks first; R CR/R CP is in last place [ 29 ]. All the SR/
MA rated “critically lo w” in the ov erall quality assess -
ment (no comprehensiv e score). As suc h, the SR/MA are
to be used as supplementar y inf or mation f or the ov erall
recommendations.
T able 3 PET/PET–CT indications (neurology): o verall recommendations
HT A (n ) No te s EB G( n) No te s Ad di o na l in fo rmaon fr om SR/M A
Al zh ei me r’ s di sease de me n a an d an y other fo rm o f de mena/ Mi ld cog ni v e impairme nt ( MCI)
No (1 ) f Routine use (A my loid tracer )
Eviden ce le ve l un cl ea r
No Ro ut in e us e ( 11 C-PI B- PET, 18 F- FD G
PET)
Se ns itivit y & sp ec ific it y of th e th ree
be ta -a my lo id ra di ot ra ce rs for
qu antita ti ve and visual an alysis ar e
compar ab le to th os e wi th ot he r
im ag in g or biom ar ke r te ch ni qu es us ed
to di ag no se AD D
No di ff eren ce s in th e di ag no st ic
accuracy of th e th re e be ta-a my lo id
radiot ra ce rs
RU (4 ) d, e, f, g 18 F- l abelled Amyloid (F lo rb et aben, Fl ut em et am ol, Fl or betapir,
NAV 469 4) and 18 F-FDG PET, PET-CT :
D/ S: PT wi th spe cific ch ar ac teri st ic s an d ca se s de sc ri bed
(different fo r th e trac er *)
Less co nt ra di ct ory, bu t ba se d on we ak eviden ce
No (5 ) a, c, d,f, g 18 F- l abelled Amyloid (F lo rb et aben, Fl ut em et am ol,
Fl or be t apir, NAV4694) an d 18 F-FD G PET, PET- CT :
D/ S: PT wi th spe cific ch ar ac teri st ic s an d ca se s de sc ri bed
(different fo r th e trac er *)
Less co nt ra di ct ory, bu t ba se d on we ak eviden ce
Un cl ea r (1 ) 18 F- FDG PET, PET-CT :
Di ag no st ic qu al it y –a bl e to de te ct te mp or op ar ie ta l
chan ge s with hi gh d egr ee of accu ra cy; marginally
su pe ri or at id enti fy in g mi dl y aff ec te d brai n re gi on s
(compa re d to SP ECT) –n o co nc re te reco mm en da ti on
gi ve n
Epil ep sy ( se iz ures )
No (1 ) Pre-surgical evalua ti on
(pot . use fu l in co njuc ti on wi th ot her imagin g
modali ti es )
RU (3 ) a, b, f Pre-surgical evalua ti on (s pe cific ca se s de sc ri bed* ),
se tt in g: sp ec . ep il ep sy cent re s
Less co nt ra di ct ory, bu t ev id en ce level only gi ve n by ACR (7 )
No (2 ) a, b D/ S: sp ec if ic ca se s de sc ri bed, e. g. ne w- on se t se iz ur e,
ne on at al se iz ur es
D/ S: PT wi th in tr ac ta bl e in fa nt il e sp as ms af te r in conclusi ve
initia l di ag no st ic –i ns uffi ci en t ev id en ce
•
•
•
ADD Alzheimer’ s disease dementia, 11C-PIB 11C-Pittsbur gh compound B radiotracer , D/S diagnostic/staging, FDG 18F-Fluordesoxy glucose
radiotracer , GL guidelines, GoR grade of recommendation, H TA healt h technology assessment, LoE le v el of evidence, MA me t a-analy sis, PT
patients, RU restricted use, SR systematic re view s
*See PET–HT A repor t 2018 [ 5 ] f or detailed cases; color coding of recommendations and lev el of contradictor ies between the e vidence sources:
see T able 1 ; number of HT A repor ts/guidelines is given in brac kets; superscript letters indicate the respective guideline: a. A CR, b. CCO, c.
ChW , d. EANM/SNMMI, e. EFNS, f. RCP/R CR, g. SNMMI/AA; LoE/GoE for appr opr iate use/inappropriate use: see Box 1; inf or mation giv en
in the table refer t o FDG PET, PET–CT , and t he use of other tracer are indicated in the table

75 Clinical and T ranslational Imaging (2019) 7:65–81
1 3
Overall r ecommendations
For recommendations of neurological indications, e vidence
identified and presented only tw o sub-indications: Alz -
heimer ’ s dementia/dementia and epilepsy (see T able 3 fo r
details).
There is a (relativ e) agreement that t here is not sufficient
e vidence in f a v our of a PET/PET–CT f or either of these
tw o sub-indications (in T able 3 highlighted red), though
prof essional societies unif or mly/consistentl y name specific
cases of AD or specific patient char acter istics that speak f or/
agains t the use of PET, depending mainl y on t he respectiv e
tracer (am yloid v s. FDG). These recommendations, ho w -
e ver , are onl y based on one source [ 55 , Update: 60 ] and
the authors t hemselv es ackno w ledge the limitations, stating
that, “ A t t he time of this revie w , e xper ience with clinical
am yloid PET imaging [w as] limited. Most published stud -
ies to date … [w ere] designed to v alidate t his technology
and understand disease mechanisms rather than to e valu -
ate applications in clinical practice. As a result, published
data are a vailable primar ily fr om highly selected popula -
tions with proto typical findings rather t han from patients
with comorbidities, complex his tor ies, and atypical f eatures
often seen in clinical practice (e7)” [ 55 ].
Equiv ocal e vidence (e.g., contradictory between HT A and
EBG in T able 3 , highlighted y ellow or blue) w as also f ound
f or t he application of PET/PET–CT in patients ha ving epi -
lepsy (again, onl y in cer tain cases, in specialized epilepsy
centres), though there is (some) consensus among t he pro -
f essional societies.
Evidenc e oninflammatory disorders
Study characteristics
In total, three HT A could be included about inflammator y
disorder indications. One f ocused on inf ections in general
from C ADTH [ 61 ], dating bac k to 2008, and tw o other
repor ts (each consis ts of a scoping repor t and an advice
statement) from SHTG/HIS (2013) f ocus on pyre xia of
unkno wn or igin and sarcoidosis [ 62 – 65 ]. Reported end -
points in the studies within these HT A repor ts ref er to diag -
nostic accuracy (mainl y f or pr imar y diagnosis).
Recommendations and non-recommendations ( n = 18)
from prof essional societies (see Bo x 1 f or abbre viations)
w ere retriev ed and e xtracted from ECCO/ESG AR [ 66 ], a
common guideline of EANM/SNMMI [ 67 ] and R CR/R CP
[ 29 ] who ga v e recommendations f or se ver al non-oncologi -
cal indications. EANM/SNMMI [ 67 ] ga v e general recom -
mendations on inflammator y disorders and ECCO/ESG AR
[ 66 ] considers inflammator y bo wel disease alone. Explicit
non-recommendations b y Choosing Wisel y [ 37 ] or NICE
Do-not-Do [ 38 ] w ere not identified.
In total, eight SR/MA w ere included f or fiv e indications
[ 68 – 75 ]. All but tw o revie ws [ 68 , 69 ] include a meta-analy sis
and consider diagnostic accuracy as the primar y endpoint.
Quality assessment
The quality of the three HT A w as rated “very good”, wit h
onl y a f e w questions that could not be judg ed “y es”. And
the quality of the three guidelines re v ealed that domain 3
[on the r igour of the guideline dev elopment (including e vi -
dence clearl y assigned to recommendations)] rang es widely ,
from 16% (R CR/RCP [ 29 ]) to 55% (ECC O/ESGAR [ 66 ]).
No tably , all guidelines w ere rated 0% with regard to edit o -
r ial independence (domain 6). The R CR/R CP [ 29 ] guideline
scored poorest on in all areas com pared to the other two. In
the ov erall rating, ECCO/ESG AR [ 66 ] ranked first of the
guidelines and all SR/MA w ere rated as “cr iticall y low”.
Overall r ecommendations
T able 4 show s t he ov erall recommendations regarding the
appropriate or inappropr iate use of PET/PET–CT f or inflam -
mator y disorder indications. There is (relativ e) consensus
around sufficient e vidence in f a v our of PET or PET–CT f or
inf ections of t he v er tebral column/spondylodiscitis. For the
f ollowing f our sub-indications, how ev er , there is contradic -
tor y or inconclusiv e evidence: periprosthetic joint inf ection,
osteom y elitis, sarcoidosis, and f ev er of unknown origin.
(2) Pilot study: evidenc e ‑based PET/PE T –C T
planning
In a second step, the recommendations derived from the
e vidence were applied (matc hed) to the hospit al data on
PET scans in one hospital (Car int hia, Aus tr ia) to gain an
understanding of the PET utilization and capacity needs.
Betw een Januar y and September 2017, 1762 PET scans were
conducted at the Clinicum Klagenfurt/Car inthia (KABEG
Management: N eeds-assessment of PET–CT at the Clinicum
Klagenfurt, June 2018, unpublished). Of those, 1370 (77.8%)
could be assigned to the three categor ies (see T ables 1 – 4 ) as
recommended b y evidence-based indications (963, 54.7%),
not recommended (311.8%) and contradictory recommenda -
tions (376, 21.3%). The other 392 (of 1762, 22.2%) could not
be allocated to an y of the t hree treatment areas due to miss -
ing inf or mation of the diagnostic code or lac k of inf or mation
from recommendations in HT A or clinical guidelines.
A sys tematic analy sis of all 1762 PET scans w as not
possible f or two reasons: firs t, all ambulator y patients who

76 Clinical and T ranslational Imaging (2019) 7:65–81
1 3
under w ent a PET scan were coded with a non-specific
diagnostic code (suc h as ‘other’ in v estig ation), so t hat the
underl ying reasons f or PET diagnosis could not be identified
and, second, no diagnostic code w as assigned to in-patients
transf er red f or t he PET scan from the other Car inthian hos -
pitals. Of t he 963 PET scans that were possible to matc h to
e vidence-based recommendations (see T able 5 ), f our ICD-
10 tumour categor ies alone accounted f or 79%: C30–C39:
T able 4 PET/PET–CT indications (inflammatory indications): ov erall recommendations
HT A (n ) No te s EB G( n) No tes A ddi o na l in fo rmaon fr om SR /M A
Im mu ne-com pr om is ed PT /p robl em ac case s
Ye s (1 ) d D/ S: si te of focal in fe con
Infe c ve en do ca rd i s (nave va lve)
Curr en tl y no t su ffic ie nt for th e di ag no si s of infe c ve endocardis
be ca us e of it s low se ns ivi ty
Infe c ve en do ca rd i s re la ted to in tr av as cu lar devi ce s, pa ce ma kers , cath et ers or pr os th ec valves
Un cl ea r (3 ) a, b, d Post -s ur ge ry (ae r a certain m e)
vs. in su ffic i ent ev id en ce /u nc le ar
As a pr om is in g im ag in g mo da li ty (a dj un cve diagnos c tool ) in
ev al ua n g PT with suspec ted CIED in fe con , PVE or IE in gen eral
Sh ould be consider ed in ca se s wh ere the diagnosis is un ce rt ai n
(PVE )
Infla mm at or y bowe l di se as e
Un cl ea r (2 ) b, c D/ S: Po o rly specifi c
Inva si ve mould infe c on s
Ye s (1 ) Help fu l in cl inic al ma na ge me nt
Limbic ence ph ali s
Sh ould be in te gr at ed wi th ot her clin ic al or im ag in g in vesgaons
(such as MR I)
Lung infe c on s
No (1 ) a Sp ec ific ca se de sc rib ed
Mulpl e in fe con i ndi ca o ns
Un cl ear (1 ) Di ga no s c qu al it y –n o recommen dao n gi ve n
Muscul oske le ta l in fe c on s –C harc ot s neur oart ho pa thy
Ye s (1 ) Gr ad in g
Muscul oske le ta l in fe c on s –C hr on ic ex trem ity /ba ck pa in
No (1 ) a D/ S: Sp ec ific ca se de sc ri be d
Muscul oske le ta l in fe c on s –C hr on ic os teomyelis of th e mandible
Ye s (1 ) Fo ll ow-u p
Muscul oske le ta l in fe c on s –I nf ec o ns of ve rt eb ra l co lumn or sp on dy lo di sc i s
Ye s (1 ) Di ag no s c qu al it y –s uper io r ac cura cy
compared wi th ot her imag in g me th od s
Ye s (1 ) b D/ S: no n- po stop er a ve Robust diagnos c te st fo r susp ec te d sp on dy lo di sci s
Muscul oske le ta l in fe c on s –J oi nt (per i- )prosthe c infe con s (e.g . knee or hi p impl ants )
•
•
•
•
•
Ye s (1 ) Di ag no s c qu al it y –s uper io r ac cura cy
compared wi th ot her imag in g me th od s
Un cl ear (2 ) a, b Cont ra di ct or yr ec ommend a on :
Sp ec ific ca se s wh ere it is no t re co mm ended
vs. un cl ea r (i nsuffi ci en t evid en ce )
May no t ye t been th e preferre d im aging te ch ni que
Muscul oske le ta l in fe c on s –O st eo my el i s of fo ot (r el at ed to di ab etes )
No (1 ) a Sp ec ific ca se de sc ri bed As po ten ally usef ul tools if combined wi th other imag ing
meth od s
Muscul oske le ta l in fe c on s –O st eo my el i s
Ye s (1 ) Di ag no s c qu al it y –s uper io r ac cura cy
compared with other imaging me th od s
No (1 ) a D/ S: Sp ecifi c case desc ri bed
PU O
No (1 ) Di ag no s c qu al it y –i nsuffi ci ent ev id en ce RU (2 ) b, d D/ S (p ri ma ry di agno si s+ di agno s c qu al it y)
Sa rc oi do si s
No (1 ) Prim ar y diag no sis (r ou n e in ve sga o n) –
in su ffic ie nt ev id en ce
RU (2 ) b, d Sp ec ific ca se s (selec ted PT ,
a er co nv . im ag in g)
Va sc ul i s
Ye s (2 ) b, d Sp ec ific ca se s de sc ri be d
Fu rthe r in di ca o ns ( no detai ls g iv en ): E va lu aon of poten ally i nfected li ver and ki dney cys ts i n polycy s c di sease;
AI DS-asso ci ated opp or tu ni s c in fe con s, associa ted tu mo rs , and Ca st le man di sease; A ssessmen t of m et aboli c ac v it y in tub er cu lo s is l es io ns; Di abe c foot inf ec o ns
No b Based on insuffic ie nt ev id en ce**
Fu rthe r in di ca o ns ( no detai ls g iv en ): M etasta c i nfec o n & of h ig h- ri sk PT with bacte re mi a
Ye s b Based on insuffic ie nt ev id en ce**
•
•
AIDS Acq uired Immune Deficiency Syndrome, AS anti-granulocyte scintigraphy , BMS bone-mor ro w scintigraphy , BS bone scintigraphy , CIED
cardio-v ascular implantable electronic device, D/S diagnostic/s taging, FDG 18 F -Fluordeso xyglucose tracer , GL guidelines, GoR g rade of recom-
mendation, H TA Health T echnology Assessment, LoE le v el of evidence, LS leukocyte scintigraph y , MA meta-analy sis, MRI magnetic resonance
imaging, PT patients, PUO Pyre xia of unknown origin, PVE prosthetic v alv e endocarditis, SR systematic re view s
*HT A repor t from 2008; **EANM/SNMMI: “ Although there is still insufficient literature f or this to be descr ibed as an evidence-based indica-
tion, we can conclude [ma jor indications], on the basis of a cumulated repor ted accuracy (> 85%) and e xper t opinion…” and “Lev el of evidence
a v ailable at t his time f or man y of these indications remains insufficient to strongl y advise the use of 18 F-FDG imaging as a first-line diagnostic
tool. ”; color coding of recommendations, and lev el of contradictories between the e vidence sources: see T able 1 ; t he number of HT A repor ts/
guidelines is giv en in brack ets; superscript letters indicate the respective guideline: a. A CR, b. ECCO/ESGAR, c. EANM/SNMMI, d. R CP/R CR:
LoE/GoE f or appropriate use/inappropr iate use: see Box1; inf or mation given in the table ref er to FDG PET , PET–CT , and the use of other tracer
are indicated in the table

77 Clinical and T ranslational Imaging (2019) 7:65–81
1 3
malignant neoplasms, respiratory system, and intratho -
racic or gans (273, 28%), C43–C44: malignant neoplasms,
skin, (224, 23%), C81–C96: malignant neoplasms, stated
or presumed to be primar y , of l ymphoid, haematopoietic
and related tissue (177, 18%), and D37–D48: neoplasms of
uncer tain or unknown beha viour (99, 10%).
The majority (22, 70%) of t he 31 PET scans not rec -
ommended within evidence-base d recommendations (see
T able 5 ) were in the f ollo wing three ICD-10 indications:
C64–C68: Malignant neoplasms, ur inar y org ans (10, 32%),
C15–C26: malignant neoplasms diges tiv e org ans (6, 19%),
and C50–C58: malignant neoplasms, breast and f emale geni -
tal org ans, respectiv ely (6, 19%).
Discussion
Summar y offindings: (1) evidence ‑based
indications andrec ommendations
Evidence assessments on PET/PET–CT ha ve been increas -
ingl y published o ver the past tw o decades in many coun -
tr ies and languages. T aking a 2004–2014 perspectiv e, the
PET–HT A 2015 report identified 155 HT A repor ts to ev alu-
ate PET or PET–CT ; e ven with a timeframe of 2008–2014,
there were s till 82 HT A a vailable. Thirty-fiv e of these were
included and e xtracted f or t heir statements on the use of
PET/PET–CT f or oncological indications. Five more r ecent
HT A on oncological (sub-)indications w ere identified dur ing
the HT A repor t update. For the new indications—f or neuro -
logical and inflammator y disorders—onl y fiv e HT A could
be considered. R ecommendations of prof essional societies
(e.g., guidelines) w ere also updated and explored f or the
three indications. A total of 234 recommendations w ere,
theref ore, included in the updated repor t. In addition, a total
of 23 SR/MA pro vided supplementar y inf or mation. Fifteen
looked onl y at oncological indications. Cost-effectiv eness of
PET s w as not an inclusion cr iter ion and w as, theref ore, not
e xplicitly consider ed; how e v er , while almost no evidence
e xists, inf or mation w as extracted from the repor ts when
there w as mention of cost-effectiv eness.
In a comparison of HT A results, the t abulated recommen -
dations of prof essional societies and SR/MA f or oncological
indications re veal that there is gener al ag reement on “sig -
nificant” indications (e.g., bronc hial carcinoma, and head
and nec k tumours) f or the use of PET/PET–CT . How e ver ,
there are significant differences in the lev el of det ail of sub-
indications and in the approach f or when a scan should not
be per f or med. There is also significant v ar iance in the reli -
ance on the access of graded pre-diagnostics.
Betw een the cur rent study and the 2015 PET–HT A repor t,
se ver al chang es in the categor ization of oncology indications
and in le vel of contr adictor y among t he e vidence sources
ha ve occur red (belo w is an o verview ; see T ables 1 , 2 , 3 , 4 ):
– Mamma carcinoma (no w recommended f or cer tain sub-
indications such as tumour r esponse assessment f or
metastatic mamma carcinoma (mainl y bone metastases),
bef ore: not recommended)
T able 5 PET scans and corresponding ICD-10 categor y matched to e vidence-based recommendations ( n = 994), Clinicum Klagenfurt/Car inthia
(KABEG Management: N eeds-assessment of PET–CT at the Clinicum Klagenfur t, June 2018, unpublished)
ICD-10 categories Recommended e vidence-based
indications
( n = 963), n (%)
No t recommended
evidence-based indica-
tions
( n = 31), n (%)
C15–C26: malignant neoplasms, diges tive or gans 28 (3) 6 (19)
C30–C39: malignant neoplasms, respiratory system and intrathoracic org ans 273 (28) –
C43–C44: malignant neoplasms, skin 224 (23) –
C50–C58: malignant neoplasms, breast, and f emale genital org ans 67 (7) 6 (19)
C60–C63: malignant neoplasms of male genital or gans – 2 (7)
C64–C68: malignant neoplasms, urinar y or gans – 10 (32)
C73–C75: malignant neoplasms, endocrine glands, and related str uctures 36 (4) 3 (10)
C76–C80: malignant neoplasms, secondar y and ill-defined 5 (< 1) 1 (3)
C81–C96: malignant neoplasms, stated or presumed to be primar y , of l ymphoid,
haematopoietic and related tissue
177 (18) –
D00–D09: insitu neoplasms – 1 (3)
D10–D36: benign neoplasms 52 (5) 2 (7)
D37–D48: neoplasms of uncer tain or unknown beha viour 99 (10) –
G30–G32: other degenerativ e diseases of t he ner v ous system 2 (< 1) –

78 Clinical and T ranslational Imaging (2019) 7:65–81
1 3
– Cervix carcinoma (not recommended, bef ore contradic -
tor y)
– T esticular , renal, and penis carcinoma (contradictory ,
bef ore not recommended)
– N ew (no t included in the PET–HT A repor t 2015): my e -
loma (recommended), neuroendocrine tumours not rec -
ommended), anal canal cancer (contradictory)
In the case of neurological indications and inflammator y
disorders, there is comparativ ely more discr epancy in t he
recommendations of prof essional societies and betw een t he
HT A and prof essional societies. There is a no t able, consist -
ent emphasis on the weak and insufficient e vidence base.
The SR/MA included in our report demonstrate this: all w ere
considered “critically lo w” in the quality assessment.
Summar y offindings: (2) pilot study
onevidence‑based PET/PE T –C T planning
Based on e vidence-based recommended and not recom -
mended indications f or mulated in step (1) of this study , a
first-e v er pilot of planning PET capacities w as conducted
and, as suc h, has no comparator .
A data-dr iven needs-assessment w as initially conducted
to pro vide a basis for an in v estment decision around the need
f or an additional PET–CT scanner in Car int hia, Austria.
First, diagnoses w ere coded according to ICD-10 classifica -
tions. Then, the 1762 PET scans per f or med between January
and September 2017 w ere matched to rele vant recommenda -
tions f or evidence-based indications/non-indications, result-
ing in 77.8% being assigned to either recommended (54.7%),
not recommended (1.8%) or contradictory (21.3%) evidence-
based indications. 22.2% could not be ascribed due to miss -
ing inf or mation of the diagnostic code or lac k of inf or mation
from recommendations in HT A or clinical guidelines. Based
on the dat a anal ysis and an additional assessment of the utili -
zation as w ell as occupancy rates, it w as decided against the
in vestment in a second PET scanner in Car int hia.
Limitations
The main strength of the presented w ork is the r igorous,
sys tematic approach applied in all s teps (e.g., double-chec k
pr inciple and quality assessment), complemented a com pre-
hensiv e, targ eted manual searc h. Ne v er t heless, the methodi -
cal process has some limitations. The systematic synthe -
sis of a vailable e vidence, whic h mainly r elies on already
aggregated e vidence, ma y result in a cer t ain loss of detailed
inf or mation. In addition, the pr imar y outcome of interest in
the dat a e xtraction w as the conclusions as ar ticulated b y the
respectiv e authors, which are different in terms of f or mula -
tion and meaning and, theref ore, difficult to compare. As a
result, a trend can be seen in the statements.
Moreo v er , the multitude of recommendations from pro -
f essional organizations necessaril y led to a capping of the
number of sources, meaning that some were no t included
and impor tant contextual insight ma y ha v e been lost. For
e xample, the S3 guidelines from the Association of Scien -
tific Medical Societies e. V . (A WMF) in Ger man y and the
guidelines from the Scottish Intercollegiate Guidelines
Ne tw ork (SIGN) w ere not included as they do no t ha v e a
specific PET/PET–CT f ocus. How e ver , they both pro vide
impor tant recommendations as t he y consider not onl y “study
e vidence”, but also detailed aspects of the diagnostic-thera -
peutic chain and differ entiate more comprehensiv el y among
tumour entities. That some guidelines w ere a pr ior i omitted
ma y lead to a potential bias (of the o v erall picture). Simi -
larl y , the heterog eneous quality of the included guidelines
ma y also result in a ske wed o v erall picture of e xistent recom -
mendations. The summar y tables make this transparent b y
assigning respectiv e recommendations to the cor responding
guidelines, ref erencing, as well, the strength of e vidence.
Finall y , in T ables 2 , 3 , and 4 of the ov erall recommenda -
tions, a differentiated consideration of tumour entities is lost.
Ne vert heless, they pr ovide an o verall pictur e t hat can be
useful (see pilot).
Reg arding the 22.2% of PET scans in Car int hia, Aus tr ia,
that could not be assigned to a recommendation in the pilot
study , one reason could be t he v er y specific indications f ound
in the evidence or a too de tailed coding. In general, while the
high number of PET scans that could not be ascr ibed to an y
categor y could be seen as limiting the explanatory/instr uctive
po wer of the pilot to use e vidence-based indication lists as
basis f or a needs-assessment and inv estment decisions, it also
sho w s clearl y that t here is a need f or impro vement of coding
indications within t he conte xt of planning of medical ser -
vices. For the final in v estment decision, fur ther inf or mation
on timing and frequency of PET utilization and occupancy
rate o v er full w ork da ys and w eek s are needed.
C onclusion
Ov erall, this study has resulted in more detailed inf or ma -
tion and specifications around PET/PET–CT indications
as compared to the 2015 PET–HT A report. This update
toge ther wit h the agg regate lis t of ov erall recommendations
f or indications as well as the explicit non-recommendations
from the 2015 PET–HT A repor t can ser v e as needs-based
and e vidence-based decision suppor t f or PET/PET–CT ser -
vice pro vision in hospitals as evidenced b y t he pilot study
in Aus tr ia. A better coding of PET utilization is needed f or
planning. Fur ther more, additional inf or mation such as tim -
ing, frequency of PET utilization, as w ell as occupancy rate

79 Clinical and T ranslational Imaging (2019) 7:65–81
1 3
o v er full w ork da ys and w eek s, is also necessar y to guide an
in vestment decision.
Acknowledgements The suppor t of Helene Eckhar dt, Fabian Dres -
senhöf er , Chr istian N am Kai Tran, and Anna Irshad in compiling the
HT A repor t is hereby gratefull y ac know ledged. W e w ould also like to
thank Kather ine Polin f or the language c heck.
F unding This study w as funded by the German Society f or Nuclear Medi -
cine (DGN) who did not ha ve an y influence on t he content of the repor t.
C ompliance with Ethical Standards
Conflict of inter est All authors declare that they ha ve no conflict of
interest.
Ethical approv al This ar ticle does not cont ain an y studies with human
par ticipants or animals per f or med b y any of the authors.
OpenAcc ess This article is distr ibuted under the ter ms of t he Crea -
tiv e Commons Attribution 4.0 Inter national License ( http://creat iveco
mmons .org/licen ses/b y/4.0/ ), which per mits unrestricted use, distr ibu -
tion, and reproduction in an y medium, pro vided you giv e appropr iate
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Why institutions use Plag.ai for originality review, entry 61

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