comparison of metaiodobenzylguanidine scintigraphy with positron emission tomography in the...
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Comparisonofmetaiodobenzylguanidinescintigraphywithpositronemissiontomographyinthediagnosticwork-upofpheochromocytomaandparaganglioma:Asystematicreview
ARTICLEinTHEQUARTERLYJOURNALOFNUCLEARMEDICINEANDMOLECULARIMAGING:OFFICIALPUBLICATIONOFTHEITALIANASSOCIATIONOFNUCLEARMEDICINE(AIMN)[AND]THEINTERNATIONALASSOCIATIONOFRADIOPHARMACOLOGY(IAR),[AND]SECTIONOFTHESOCIETYOF..·JUNE2013
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VittoriaRufini
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122 THEQUARTERLYJOURNALOFNUCLEARMEDICINEANDMOLECULARIMAGING June2013
Functionalimagingisanimportantstepinthedi-agnosticapproachofpatientswithpheochromo-
cytomaandparaganglioma(Pheo/PGL).Itallows1)confirmationofdiagnosisofPheo/PGL,ifaspecifictracer isused;2)stagingat initialpresentation, i.e.searchofmetastaticdisease;3)restagingaftercom-pletionoftreatmentinpatientsatriskofrecurrence;4) selection for targeted radionuclide therapywithiodine-131 metaiodobenzylguanidine (I-131-MIBG)orYttrium-90/Lutetium-177somatostatinanalogues;and5)evaluationofmetabolicresponsetotherapy.1After more than 30 years of experience, scintigra-phy with [131I]MIBG or [123I]MIBG is still the mostwidespreadfunctionalimagingtechniqueforPheo/PGL,duetoitstissuespecificity,goodsensitivityandworldwide availability.2 Imagingof Pheo/PGLwithMIBGisbasedontheexpressionofcellmembranenorepinephrine transporters (NET) and vesicularmonoamine transporters (VMAT) in these tumors.3Worldwideexperiencehasproved thatMIBGscin-tigraphycanlocatePheo/PGLofalltypes,includingadrenalandextra-adrenaltumors,metastaticdiseaseandvariousfamilialsyndromesassociatedwithPheo/PGL.4-6Theoverallsensitivityandspecificityof[131I]MIBGscintigraphyinPheo/PGLishigh(sensitivity:77-90%, specificity: 95-100%); sensitivity improveswiththeuseof[123I]MIBGandSPECT(88-96%).1,4,7However,recentstudiesindicatethatMIBGscintig-raphyyieldspoorresultsespeciallyinfamilialPheo/PGLsyndromes,malignantlesions(57-79%sensitiv-ity), extra-adrenal abdominal PGL, andnon-secret-
Institute of Nuclear Medicine Università Cattolica del Sacro Cuore, Roma, Italy
QJNUCLMEDMOLIMAGING2013;57:122-33
V.RUFINI,G.TREGLIA,P.CASTALDI,G.PEROTTI,A.GIORDANO
Comparison of metaiodobenzylguanidine scintigraphy with positron emission tomography in the diagnostic work-up of pheochromocytoma and paraganglioma: a systematic review
Aim. The aim of this paper was to systematically re-view published data about the comparison of radiola-belled metaiodobenzylguanidine (MIBG) scintigraphy and positron emission tomography (PET) with diffe-rent radiopharmaceuticals in patients with pheochro-mocytoma and paraganglioma (Pheo/PGL).Methods. A comprehensive literature search of studies published in PubMed/MEDLINE and Embase databa-ses through September 2012 and regarding MIBG scin-tigraphy and PET imaging with different radiopharma-ceuticals in patients with Pheo/PGL was carried out.Results. Twenty-eight studies comprising 852 patients who underwent both MIBG scintigraphy and PET or PET/CT with different radiopharmaceuticals were in-cluded and discussed. Three studies evaluated carbon-11-hydroxyephedrine ([11C]HED) as PET radiophar-maceutical, nine studies fluorine-18-dopamine ([18F]DA), eight studies fluorine-18-dihydroxyphenylalani-ne ([18F]DOPA), twelve studies fluorine-18-fluorodeo-xyglucose ([18F]FDG) and five studies gallium-68-so-matostatin analogues.Conclusions. Despite the heterogeneity of the studies included in the analysis, it can be concluded that the diagnostic performance of PET with various agents is clearly superior to that of MIBG scintigraphy in patients with Pheo/PGL, mainly for familial, extra-adrenal and metastatic diseases; however, MIBG main-tains a unique role in selecting patients suitable for 131I-MBG therapy. Further larger prospective studies comparing MIBG and different PET tracers in patients with Pheo/PGL as well as a cost-effectiveness analysis of the two techniques are needed.Key words: Positronemissiontomography-3-iodobenzyl-guanidine -Pheochromocytoma -Paraganglioma -Neuralcresttumor.
Corresponding author: V. Rufini, Nuclear Medicine Institute, Poli-clinicoUniversitarioA.Gemelli,LargoA.Gemelli8,00168Rome,Italy.E-mail:[email protected]
Anno: 2013Mese: JuneVolume: 57No: 2Rivista: THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGINGCod Rivista: Q J NUCL MED MOL IMAGING
Lavoro: 2591-JNUtitolo breve: COMPARISON OF MIBG SCINTIGRAPHY WITH PET IN THE DIAGNOSTIC WORK-UP OF PHEOCHROMOCYTOMA AND PARAGANGLIOMAprimo autore: RUFINIpagine: 122-33
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COMPARISONOFMIBGSCINTIGRAPHYWITHPETINTHEDIAGNOSTICWORK-UPOFPHEOCHROMOCYTOMAANDPARAGANGLIOMA RUFINI
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Lavoro: 2591-JNUtitolo breve: COMPARISON OF MIBG SCINTIGRAPHY WITH PET IN THE DIAGNOSTIC WORK-UP OF PHEOCHROMOCYTOMA AND PARAGANGLIOMAprimo autore: RUFINIpagine: 122-33
riedout tofind relevantpeer reviewedarticlesonthe comparison of MIBG scintigraphy and PET orPET/CT with different radiopharmaceuticals in pa-tientswithPheo/PGL.Asearchalgorithmbasedonacombinationof the terms:a)‘‘PET’’OR“positronemission tomography”ANDb)“MIBG”or“metaio-dobenzylguanidine” was used. No beginning datelimitwasusedandthesearchwasupdateduntilSep-tember25th,2012.Toexpandoursearch,referencesoftheretrievedarticleswerealsoscreenedforaddi-tionalstudies.Nolanguagerestrictionwasused.AllstudiesorsubsetsinstudieswhichcomparedMIBGscintigraphy andPETorPET/CTwithdifferent ra-diopharmaceuticalsinpatientswithPheo/PGLwereeligibleforinclusion.Articlesthatareexcludedfromthis studywere thearticles thatarenotwithin thefieldofinterestofthisreview;thereviewarticles,ed-itorialsorletters,comments,conferenceproceedingsandthecasereportsandsmallcaseseries.Twore-searchers(GTandVR)independentlyreviewedthetitlesandtheabstractsoftheretrievedarticles,apply-ing the inclusion and exclusion criteriamentionedabove. The same two researchers then independ-entlyreviewedthefull-textversionofthearticlestoconfirmtheireligibilityforinclusion.Disagreementswereresolvedinaconsensusmeeting.Foreachin-cludedstudy,informationwascollectedconcerningbasicstudy(authornames,journal,yearofpublica-tion,countryoforigin,studydesign),patientchar-acteristics (number of patients, gender and meanage),andtechnicalaspectsaboutMIBGscintigraphyandPETimaging(deviceused,radiopharmaceuticalsused, injected activity, time between injection andacquisition,acquisitionprotocol,imageanalysisandreferencestandardused),andtheresults.
Results
The comprehensive computer literature searchfromthePubMed/MEDLINEandEmbasedatabasesrevealed329articles.Reviewingtitlesandabstracts,303articleswereexcludedapplyingthecriteriamen-tionedabove.Twenty-eightstudiescomprising852patientswhounderwentbothMIBGscintigraphyandPETorPET/CTwithdifferentradiopharmaceuticalswereselectedandretrievedinfull-textversion.10,11,
16-41Noadditionalstudywasfoundbyscreeningthereferences of these articles. The characteristics ofthe28studiesincludedinthisreviewarepresentedin Tables I-III. Three studies evaluated carbon-11-
ingtumorsintheheadandneckregion.1,8-11Aparttheoccurrenceoffalsenegativeresultsintheabovementionedconditions,thereareotherlimitationsintheuseofMIBGscintigraphy,whichare:1)practi-cal limitations, such as need for thyroid blockadeandwithdrawalofinterferingmedications,andlongimagingtime;2)technicallimitations,suchasSPECTimageswithlowresolutionandquantificationofup-takenoteasily feasible;3)pitfalls in interpretation,suchasgastrointestinaltractartifacts,whichcouldbepartlysolvedbySPECT/CTimaging.12
Awide range of PET tracers, both specific andnon-specificforchromaffintumors,havebeenpro-posedforimagingPheo/PGL.6,13,14PETtracersin-cludespecificagents,suchas[11C]hydroxyephedrine,[18F]fluorodihydroxyphenilalanine, [18F]dopamineand[124I]MIBG(thelattercurrentlyusedmainlyfordosimetricpurposes);13, 15 andnon-specific agents,suchas[68Ga]labeledsomatostatinanalogues(soma-tostatinreceptorstatus)and[18F]fluorodeoxyglucose(glucose metabolism).13, 14 In general, PET tracersprovide excellent tumor imagingwith a tumor-to-background ratio greater than that observed with[123I]MIBG. The higher spatial resolution of PETtechnologyallowsdetectingmorelesionswithhigh-er contrast. Also, PET tracer uptake can be easilyquantified by calculating the standardized uptakevalue(SUV).OtheradvantagesofPET/CTimagingoverMIBGscintigraphyincludelessradiationexpo-sure,noneedofthyroidblockadeorofwithdrawingmedication formanyof them,andshorter timeofimaging.However,exceptfor[18F]FDG,PETagentshavenotyet awidespreadclinicalusedue to thehighcostandlimitedavailability,lackofofficialap-provalandreimbursement.Thus,almostallofthemcanbeusedonlyinthecontextofapprovedclinicaltrialsasanexperimentalresearchtool.
Todate,asystematicreviewarticleaboutthecom-parisonofMIBGscintigraphyandPETwithdifferentradiopharmaceuticals inpatientswithPheo/PGL islacking in the literature.Theaimof this review isthusmakeasystematicreviewinthecomparisonofpublishedMIBGandPET/CTimagingresultstoup-dateandanalyzethecurrentevidencefortheuseofMIBGscintigraphyandPETimaginginthissetting.
Materials and methods
AcomprehensivecomputerliteraturesearchofthePubMed/MEDLINEandEmbasedatabaseswascar-
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124 THEQUARTERLYJOURNALOFNUCLEARMEDICINEANDMOLECULARIMAGING June2013
and 2 patients both radiopharmaceuticals. Com-paredtoMIBGscintigraphy,PETscanningwith[11C]HEDdetectedmorelesionswithhighercontrast.Alllesions that were identified by MIBG scintigraphywere detected by [11C]HED PET. Image quality of[11C]HEDPETwasexcellentandsuperiortothatob-tainedfromplanarandtomographicMIBGstudies.Theuptakeof[11C]HEDintoPheowasrapid.There-fore,theseauthorsconcludedthat[11C]HEDPETisapromisingapproachtothedetectionofPheo.How-ever,theavailabilityofthisPETtracerislimited,thesynthesisisrelativelycomplexandtheshorthalf-lifeof[11C]requiresonsiteproductionforeachpatient.16
In2006,Franziuset al. demonstratedthefeasibil-ityof[11C]HEDPET/CTforexaminationoftumorsof
hydroxyephedrine([11C]HED)asPETradiopharma-ceutical, 9 studies fluorine-18-dopamine ([18F]DA),8 studies fluorine-18-dihydroxyphenylalanine ([18F]DOPA), 12 studies fluorine-18-fluorodeoxyglucose([18F]FDG) and 5 studies gallium-68-somatostatinanalogues([68Ga]somatostatinanalogues).Eightoutof28studiesevaluatedatleasttwodifferentPETra-diopharmaceuticalscomparedtoMIBGscintigraphy.
MIBG versus [11C]HED
Firstofall,in1992,Shulkinet al. compared[123/131I]MIBGscintigraphywith[11C]HEDPETintenpatientswith known or suspected Pheo.16 Three patientsreceived [131I]MIBG, 5patients received [123I]MIBG,
Table I.—�Basic studies and patient characteristics.
Authors Year Country Studydesign
PGpatientsperforming
PETandMIBGscintigraphy
Meanage
(years)%Male Tracersused
Shulkinet al.16 1992 USA NR 10 45.1 80% 123/131I-MIBG,11C-HEDShulkinet al.17 1999 USA NR 29 45.3 62% 123/131I-MIBG,18F-FDGLeRestet al.18 2001 UK Retrospective 4 NR NR 123I-MIBG,18F-FDG,111In-DTPA-OctHoegerleet al.19 2002 Austria NR 14 44 64% 123I-MIBG,18F-DOPAIliaset al.10 2003 USA Prospective 16 38.2 62% 131I-MIBG,18F-DAFranziuset al.20 2006 Germany NR 7 49 57% 123I-MIBG,11C-HEDMamedeet al.21 2006 USA Retrospective 5 44.6 20% 123I-MIBG,18F-FDG,18F-DAMannet al.22 2006 USA Retrospective 14 45 57% 131I-MIBG,18F-FDG,11C-HEDKajiet al.23 2007 USA Prospective 7 37 57% 123/131I-MIBG,18F-DATimmerset al.24 2007 USA&Nederland Retrospective 30 38.2 53% 123/131I-MIBG,18F-FDG,18F-DA,
111In-DTPA-Oct,99mTc-MDPWinet al.25 2007 UK Retrospective 5 51 60% 123I-MIBG,68Ga-DOTATATEIliaset al.26 2008 USA Retrospective 53 44.2 47% 123I-MIBG,18F-DA,111In-DTPA-OctTaiebet al.27 2008 France Retrospective 9 50.9 89% 131I-MIBG,18F-FDG,18F-DOPA,
111In-DTPA-OctTakanoet al.28 2008 Japan Prospective 11 39.9 55% 123I-MIBG,18F-FDGZelinkaet al.29 2008 USA&CzechRepublic Retrospective 71 36 53% 123/131I-MIBG,18F-FDG,18F-DA,99mTc-MDPFiebrichet al.30 2009 Nederland Prospective 48 46 42% 123I-MIBG,18F-DOPATimmerset al.31 2009 USA&Nederland Prospective 52 46.8 54% 123I-MIBG,18F-FDG,18F-DOPA,18F-DATimmerset al.32 2009 USA&Nederland Prospective 99 46.4 35% 123/131I-MIBG,18F-DAFottneret al.33 2010 Germany Prospective 30 42 47% 123I-MIBG,18F-DOPACharrieret al.34 2011 France Prospective 25 NR 56% 131I-MIBG,18F-FDG,18F-DOPA,111In-
DTPA-OctKinget al.11 2011 USA Prospective 10 38.4 90% 123I-MIBG,18F-FDG,18F-DOPA,18F-DA,
111In-DTPA-OctKroisset al.35 2011 Austria Retrospective 6 49.2 50% 123I-MIBG,68Ga-DOTATOCNajiet al.36 2011 UK Retrospective 11 NR 83% 123I-MIBG,68Ga-DOTATATERufiniet al.37 2011 Italy Retrospective 12 47 50% 131I-MIBG,18F-DOPAMauriceet al.38 2012 UK Retrospective 15 38.3 NR 123I-MIBG,68Ga-DOTATATENakanoet al.39 2012 Japan NR 8 57.3 50% 123I-MIBG,18F-FDGNaswaet al.40 2012 India Prospective 35 34.4 62.8% 131I-MIBG,68Ga-DOTANOCNaswaet al.40 2012 India Prospective 35 34.4 62.8% 131I-MIBG,68Ga-DOTANOCTimmerset al.41 2012 USA Prospective 216 45.2 49% 123I-MIBG,18F-FDG
NR:notreported.
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Table II.—�Technical aspects of the studies which used MIBG scintigraphy for detecting pheochromocytomas/paragangliomas.
Authors Deviceused Tracersused Injectedactivity
Timebetweentracerinjectionandimageacquisition(hours)
Acquisitionprotocol Referencestandard
Shulkinet al.16 SPECT 123/131I-MIBG 18.5MBq(131I-MIBG);370MBq(123I-MIBG)
24,48and72(131I-MIBG)2,24and48(123I-MIBG)
Planarandtomographic
NR
Shulkinet al.17 SPECT 123/131I-MIBG 19-38MBq(131I-MIBG);370MBq(123I-MIBG)
24,48and72(131I-MIBG)18-24and48(123I-MIBG)
Planarandtomographic
NR
LeRestet al.18 γcamera 123I-MIBG 200MBq 1,4,24and48 Planar NRHoegerleet al.19 SPECT 123I-MIBG 170MBq 24and48 Planarand
tomographicHistologyand/
orclinical/imagingfollow-up
Iliaset al.10 γcamera 131I-MIBG 18.5MBq 24and48 Planar Histologyand/orclinical/imaging
follow-upFranziuset al.20 SPECT/CT 123I-MIBG NR 4and24 Planarand
tomographicHistologyand/
orclinical/imagingfollow-up
Mamedeet al.21 SPECT 123I-MIBG 370MBq 24and48 Planarandtomographic
Histologyand/orclinical/imaging
follow-upMannet al.22 SPECT 131I-MIBG 18.5MBq 24and48 Planarand
tomographicHistologyand/
orclinical/imagingfollow-up
Kajiet al.23 SPECT 123/131I-MIBG 18.5MBq(131I-MIBG);370MBq(123I-MIBG)
24and48 Planarandtomographic
Histology
Timmerset al.24 SPECT 123/131I-MIBG 18.5MBq(131I-MIBG);370MBq(123I-MIBG)
24and48 Planarandtomographic
Histologyand/orclinical/imaging
follow-upWinet al.25 SPECT 123I-MIBG 370MBq 4and24 Planarand
tomographicHistologyand/
orclinical/imagingfollow-up
Iliaset al.26 SPECT/CT 123I-MIBG 370MBq 24and48 Planarandtomographic
Imaging
Taiebet al.27 SPECT 131I-MIBG NR NR Planarandtomographic
NR
Takanoet al.28 γcamera 123I-MIBG 222MBq 6and24 Planar Histologyand/orclinical/imaging
follow-upZelinkaet al.29 SPECT 123/131I-MIBG 18.5MBq(131I-MIBG);
370MBq(123I-MIBG)24and48 Planarand
tomographicClinical/imaging
follow-upFiebrichet al.30 SPECT 123I-MIBG 200-370MBq 4,24and48 Planarand
tomographicHistologyand/
orclinical/imagingfollow-up
Timmerset al.31 SPECT 123I-MIBG 370MBq(123I-MIBG) 24and48 Planarandtomographic
Histologyand/orclinical/imaging
follow-upTimmerset al.32 SPECT 123/131I-MIBG 18.5MBq(131I-MIBG);
370MBq(123I-MIBG)24and48 Planarand
tomographicHistologyand/orClinical/imaging
follow-upFottneret al.33 SPECT 123I-MIBG 250MBq 4and24 Planarand
tomographicHistologyand/
orclinical/imagingfollow-up
Charrieret al.34 SPECT 131I-MIBG NR NR Planarandtomographic
Histologyand/orclinical/imaging
follow-upKinget al.11 SPECT/CT 123I-MIBG 370MBq 24 Planarand
tomographicHistologyand/
orclinical/imagingfollow-up
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he c
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he A
rtic
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he p
rodu
ctio
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rints
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rmitt
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RUFINI COMPARISONOFMIBGSCINTIGRAPHYWITHPETINTHEDIAGNOSTICWORK-UPOFPHEOCHROMOCYTOMAANDPARAGANGLIOMA
126 THEQUARTERLYJOURNALOFNUCLEARMEDICINEANDMOLECULARIMAGING June2013
uptakewereshownbyboth[18F]FDAPETand[131I]MIBG, 90 only by [18F]FDA, and 10 only by [131I]MIBG.10 In 2006,Mamede et al. compared [18F]DAPETand [123I]MIBGscintigraphy in5patientswithmetastaticPheo.Theyfoundthatalllesionsseenon[123I]MIBGscansweredetectedon[18F]DAPET.Ad-ditionallesionswerealsodetectedbyPETimaging.Nonetheless, [18F]DA failed to detect some lesionsseenonCTandMRI.21
Kajiet al. investigatedwhether [18F]DAPETwasmoreeffectivethan[123/131I]MIBGscintigraphyinthelocalizationofvonHippelLindausyndrome-relatedPheo. [18F]DAPET localizedPheo in all 7patientswithvonHippelLindausyndrome.Incontrast,threeout of the seven patients had negative results at[123/131I]MIBG scintigraphy. Therefore, [18F]DA PETwas found tohave a superior diagnostic accuracyover[123/131I]MIBGscintigraphyinthediagnosticlo-calization of von Hippel Lindau syndrome-relatedPheo.23
In2007,Timmerset al. foundthatin30patientswith succinatedehydrogenasecomplex, subunitB(SDHB) related PGL, the sensitivity of [123I]MIBGscintigraphyand[18F]DAPETonaperpatient-based
thesympatheticnervoussystem(includingfivePheoandtwoPGL)andcomparedtheresultswith [123I]MIBGscintigraphy.[11C]HEDPET/CTdetectedmorelesions(80of81;sensitivity:99%)comparedto[123I]MIBGscintigraphy(75of81;sensitivity:93%).Withbothmethods,therewerenofalse-positivelesions.20
AlsoMannet al. demonstratedintheirstudyin14patientswithsuspectedPheothat[11C]HEDPETim-agingoffersimprovedimagequalityandresolutionover[131I]MIBGscintigraphy.[11C]HEDPETdetectedmore lesions compared to [131I]MIBG scintigraphy,significantlyinfluencingtheclinicalmanagementofthesepatients.22
MIBG versus [18F]DA
Allstudiesthatevaluatedthediagnosticperform-anceof[18F]DAPETwereperformedattheNationalInstitute of Health of Bethesda (Maryland, USA).First of all, in 2003, Ilias et al. assessed the diag-nosticutilityof[18F]DAPETcomparedto[131I]MIBGscintigraphyin16patientswithmetastaticPheo.[18F]DAPETlocalizedPheoinallpatients,but7patientshad negative [131I]MIBG scans. Thirty-eight foci of
Table II.—�Technical aspects of the studies which used MIBG scintigraphy for detecting pheochromocytomas/paragangliomas.
Authors Deviceused Tracersused Injectedactivity
Timebetweentracerinjectionandimageacquisition(hours)
Acquisitionprotocol Referencestandard
Kroisset al.35 SPECT 123I-MIBG NR 24and48 Planarandtomographic
Histologyand/orclinical/imaging
follow-upNajiet al.36 SPECT 123I-MIBG 370MBq 4and24 Planarand
tomographicHistologyand/
orclinical/imagingfollow-up
Rufiniet al.37 SPECT/CT 123I-MIBG 260-370MBq 24 Planarandtomographic
Histologyand/orclinical/imaging
follow-upMauriceet al.38 SPECT 123I-MIBG 370MBq 4and24 Planarand
tomographicHistologyand/
orclinical/imagingfollow-up
Nakanoet al.39 γcamera 123I-MIBG 222MBq 6and24 Planar Histologyand/orclinical/imaging
follow-upNaswaet al.40 SPECT 131I-MIBG 37MBq 24and48 Planarand
tomographicHistologyand/
orclinical/imagingfollow-up
Timmerset al.41 SPECT/CT 123I-MIBG 370MBq 24and48 Planarandtomographic
Histologyand/orclinical/imaging
follow-upShulkinet al.16 SPECT 123/131I-MIBG 18.5MBq(131I-MIBG);
370MBq(123I-MIBG)24,48and72(131I-MIBG)2,24and48(123I-MIBG)
Planarandtomographic
NR
NR:notreported.
Table II.—�Continues from previous page.
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Vol.57-No.2 THEQUARTERLYJOURNALOFNUCLEARMEDICINEANDMOLECULARIMAGING 127
Table III.—�Technical aspects of the studies which used PET with different tracers for detecting pheochromocytomas/paragangliomas.
Authors Deviceused
Tracersused Injectedactivity
Timebetweentracerinjection
andimageacquisition(min)
PETacquisitionprotocol Imageanalysis Referencestandard
Shulkinet al.16 PET 11C-HED 740MBq 0 staticacquisition Qualitativeandsemiquantitative
NR
Shulkinet al.17 PET 18F-FDG 370MBq 0or45 dynamicandstaticacquisition
Qualitativeandsemiquantitative
NR
LeRestet al.18 PET 18F-FDG 350MBq 45 staticacquisition Qualitative NRHoegerleet al.19
PET 18F-DOPA 220MBq 90 staticacquisition Qualitative Histologyand/orclinical/imagingfollow-up
Iliaset al.10 PET 18F-DA 37MBq 0 staticacquisition Qualitative NRFranziuset al.20 PET/CT 11C-HED 320MBq 5 staticacquisition Qualitativeand
semiquantitativeHistologyand/orclinical/
imagingfollow-upMamedeet al.21 PETand
PET/CT
18F-DAand18F-FDG
38MBq(18F-DA)and458MBq
(18F-FDG)
3(18F-DA)and60(18F-FDG)
staticacquisition Qualitativeandsemiquantitative
Histologyand/orclinical/imagingfollow-up
Mannet al.22 PET 18C-mHEDand
18F-FDG
7.4MBq/Kg(11C-mHED
and370MBq(18F-FDG)
0(11C-mHED18F-FDG)
dynamicandstaticacquisition
Qualitativeandsemiquantitative
Histologyand/orclinical/imagingfollow-up
Kajiet al.23 PET 18F-DA 37MBq NR staticacquisition Qualitative HistologyTimmerset al.24 PETand
PET/CT
18F-DAand18F-FDG
37MBq(18F-DA)and555MBq
(18F-FDG)
3(18F-DA)and60(18F-FDG)
staticacquisition Qualitativeandsemiquantitative
Histologyand/orclinical/imagingfollow-up
Winet al.25 PET 68Ga-DOTATATE
99MBq 30 staticacquisition Qualitativeandsemiquantitative
Histologyand/orclinical/imagingfollow-up
Iliaset al.26 PET 18F-DA 37MBq 0 staticacquisition Qualitative ImagingTaiebet al.27 PET/CT 18F-DOPA
and18F-FDG
285MBq(18F-DOPA)
and370MBq(18F-FDG)
10-20(18F-DOPA)and60(18F-FDG)
staticacquisition Qualitativeandsemiquantitative
Histologyand/orclinical/imagingfollow-up
Takanoet al.28 PET 18F-FDG 5MBq/Kg 50 staticacquisition Qualitativeandsemiquantitative
Histologyand/orclinical/imagingfollow-up
Zelinkaet al.29 PETandPET/CT
18F-DAand18F-FDG
37MBq(18F-DA)and555MBq
(18F-FDG)
3-10(18F-DA)and60(18F-FDG)
staticacquisition Qualitative Clinical/imagingfollow-up
Fiebrichet al.30 PET/CT 18F-DOPA 180MBq 60 staticacquisition Qualitativeandsemiquantitative
Histologyand/orclinical/imagingfollow-up
Timmerset al.31 PETandPET/CT
18F-DOPA,18F-DAand
18F-FDG
460MBq(18F-DOPA),37MBq(18F-DA)and555MBq
(18F-FDG)
30(18F-DOPA),3(18F-DA)and60(18F-FDG)
staticacquisition Qualitativeandsemiquantitative
Histologyand/orclinical/imagingfollow-up
Timmerset al.32 PET 18F-DA 37MBq 0 staticacquisition Qualitative Histologyand/orclinical/imagingfollow-up
Fottneret al.33 PET 18F-DOPA 238MBq 60-80 staticacquisition Qualitative Histologyand/orclinical/imagingfollow-up
Charrieret al.34 PET/CT 18F-DOPAand
18F-FDG
4MBq/Kg 60-90 staticacquisition Qualitativeandsemiquantitative
Histologyand/orclinical/imagingfollow-up
Kinget al.11 PETandPET/CT
18F-DOPA,18F-DAand
18F-FDG
444MBq(18F-DOPA),37MBq(18F-DA)and555MBq
(18F-FDG)
30(18F-DOPA),10(18F-DA)and60(18F-FDG)
staticacquisition Qualitative Histologyand/orclinical/imagingfollow-up
Kroisset al.35 PET 68Ga-DOTATOC
NR 60-90 staticacquisition Qualitative Histologyand/orclinical/imagingfollow-up
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he c
reat
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of d
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ativ
e w
orks
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he A
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mitt
ed.T
he p
rodu
ctio
n of
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rints
for
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onal
or
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mer
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rmitt
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t is
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o re
mov
e, c
over
, ov
erla
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bscu
re,
bloc
k, o
r ch
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RUFINI COMPARISONOFMIBGSCINTIGRAPHYWITHPETINTHEDIAGNOSTICWORK-UPOFPHEOCHROMOCYTOMAANDPARAGANGLIOMA
128 THEQUARTERLYJOURNALOFNUCLEARMEDICINEANDMOLECULARIMAGING June2013
tothatof[18F]DOPAPET(100%)indetectingheadandneckPG.11
MIBG versus [18F]DOPA
AsthefirsteffortofusingF-18FDOPAPETforthediagnosticworkupofPheo,Hoegerleet al. in2002demonstratedthat[18F]DOPAPETisahighlysensi-tiveandspecifictechniqueforthedetectionofPheo.Theseauthorscomparedthediagnosticaccuracyof[18F]DOPAPETand[123I]MIBGscintigraphyin14pa-tientswithPheo.Sensitivitywas100%for[18F]DOPAPETand71%for[123I]MIBGscintigraphy;specificitywas100%forbothprocedures.19ThegroupofTaiebet al. evaluatedsomepatientswithPGLorPheobyusing[18F]DOPAPET.InpatientswithmalignantPGLorPheo,[18F]DOPAPETidentifiedadditionallesionscompared to the conventional work-up including[131I]MIBGscans.However,theseauthorssuggestedthat[131I]MIBGscintigraphyhasstillaroleinpatientswithPGLandPheo,as[131I]MIBGand[18F]DOPAim-agesdidnotcompletelyoverlap.27
Fiebrichet al. demonstratedthesuperiorityof[18F]DOPAPETcompared to [123I]MIBGscintigraphy in48patientswithknownorsuspectedPheoorPGL.Patient-based sensitivities for [18F]DOPA PET and[123I]MIBGscintigraphywere90%and65%,respec-tively. Lesion-based sensitivities for [18F]DOPAPETand[123I]MIBGscintigraphywere73%and48%,re-spectively.30
analysiswas80%and88%, respectively.These re-sultswere,inferiortothatof[18F]FDGPET(100%).24
In2008,Iliaset al. evaluated53patientswithPheoandconfirmedthesuperiordiagnosticperformanceof [18F]DAPETover [123I]MIBGscintigraphy in thissetting. In fact, theseauthors foundanoverallperpatient-based sensitivity of 90.2% for [18F]DA PETand76%for[123I]MIBGscintigraphy.26
In their retrospective study,Zelinkaet al. foundthat [18F]DAPETdemonstrated a higher sensitivity(90%)indetectingbonemetastasesinpatientswithPheoandPGLwhencomparedto[123/131I]MIBGscin-tigraphy(71%).29Evaluatingalargeseriesofpatientswith known or suspected Pheo or PGL, Timmerset al. demonstratedthatfortumorlocalization,[18F]DA PET and [123/131I]MIBG scintigraphy performedequally well in patients with non-metastatic PGL,butmetastasesweredetectedwithahigher sensi-tivityby [18F]DAPETthanby [123/131I]MIBGscintig-raphy(97%versus85%,respectively).32Theoverallsensitivityof[18F]DAPETindetectingPheoorPGLwassuperiorcomparedtothatof[123/131I]MIBGscin-tigraphy(92%versus70%,respectively).Theoverallspecificityof[18F]DAPET(90%)washoweverlowerwhencomparedtothatof[123/131I]MIBGscintigraphy(100%).32
Recently, King et al. evaluated 10 patients withSDHx-relatedheadandneckPGLandfoundalow-erper lesion-basedsensitivityofboth [18F]DAPET(46%)and[123/I]MIBGscintigraphy(31%)compared
Table III.—�Technical aspects of the studies which used PET with different tracers for detecting pheochromocytomas/paragangliomas.
Authors Deviceused
Tracersused Injectedactivity
Timebetweentracerinjection
andimageacquisition(min)
PETacquisitionprotocol Imageanalysis Referencestandard
Najiet al.36 PET 68Ga-DOTATATE
370MBq 30 staticacquisition Qualitative Histologyand/orclinical/imagingfollow-up
Rufiniet al.37 PET/CT 18F-DOPA 165-370MBq 60 staticacquisition Qualitativeandsemiquantitative
Histologyand/orclinical/imagingfollow-up
Mauriceet al.38 PET/CT 68Ga-DOTATATE
150MBq 30 staticacquisition Qualitative Histologyand/orclinical/imagingfollow-up
Nakanoet al.39 PET/CT 18F-FDG 5MBq/Kg NR staticacquisition Qualitativeandsemiquantitative
Histologyand/orclinical/imagingfollow-up
Naswaet al.40 PET/CT 68Ga-DOTANOC
132-222 45-60 staticacquisition Qualitative Histologyand/orclinical/imagingfollow-up
Timmerset al.41 PET/CT 18F-FDG 555MBq 60 staticacquisition Qualitativeandsemiquantitative
Histologyand/orclinical/imagingfollow-up
Shulkinet al.16 PET 11C-HED 740MBq 0 staticacquisition Qualitativeandsemiquantitative
NR
NR:notreported
Table III.—�Continues from previous page.
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se t
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and
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onl
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y of
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s A
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o m
ake
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ies
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er s
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dica
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r sy
stem
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, ei
ther
prin
ted
or e
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roni
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e A
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rpos
e.It
is n
ot p
erm
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to
dist
ribut
e th
e el
ectr
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cop
y of
the
art
icle
thr
ough
onl
ine
inte
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and
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intr
anet
file
sha
ring
syst
ems,
ele
ctro
nic
mai
ling
or a
ny o
ther
mea
ns w
hich
may
allo
w a
cces
s to
the
Art
icle
.The
use
of
all o
r an
y pa
rt o
f th
e A
rtic
le fo
r an
y C
omm
erci
al U
se is
not
per
mitt
ed.T
he c
reat
ion
of d
eriv
ativ
e w
orks
fro
m t
he A
rtic
le is
not
per
mitt
ed.T
he p
rodu
ctio
n of
rep
rints
for
pers
onal
or
com
mer
cial
use
isno
t pe
rmitt
ed.I
t is
not
per
mitt
ed t
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pared to [123I]MIBG scintigraphy. Furthermore, so-matostatinreceptorPETmaybeuseful toevaluatethosepatientswhoaresuitablefortherapywithra-diolabelledsomatostatinanalogues.25ThesefindingswereconfirmedbyotherreportsofthesamegroupevaluatingagreaternumberofpatientswithPheoor PG.36, 38 In particular,Maurice et al. found dis-cordantfindingsbetween[68Ga]DOTATATEPET/CTand[123I]MIBGscintigraphyin7of15patientswithPheoorPGLincludedintheirstudy.Theseauthorssuggestedthat [68Ga]DOTATATEPET/CTshouldbeconsideredasafirst-lineinvestigationinpatientsathighriskofPGandmetastaticdisease,suchasinthescreeningofcarriers formutationsassociatedwithfamilial PG syndromes. Furthermore, if 123I-MIBGscintigraphydidnotdetectlesionsinpatientswithahighpretestprobabilityofPheoorPGL,[68Ga]DO-TATATEPET/CTshouldbeconsideredas thenextinvestigation.38
Recently,Kroisset al. compared theaccuracyof[123I]MIBGscintigraphyand[68Ga]DOTATOCPETinthediagnosisandstagingof6patientswithmeta-staticPheo.Onaper-patientbasis,both[68Ga]DO-TATOCPETand [123I]MIBG scintigraphy showedasensitivityof100%,whencomparedwithanatomicalimaging.However, on a per-lesion basis, the sen-sitivity of [68Ga]DOTATOCPETwas superior com-paredtothatof[123I]MIBGscintigraphy(91.7%ver-sus63.3%,respectively).35
Lastly,intheirprospectivestudy,Naswaet al. com-pared[68Ga]DOTANOCPET/CTwith[131I]MIBGscin-tigraphy in25patientswithPheoorPGL,demon-stratingthatsomatostatinreceptorPET/CTishighlysensitiveandspecificforthedetectionofthesetu-mors. Thediagnostic accuracyof [68Ga]DOTANOCPET/CTinthissettingseemstobesuperiortothatof[131I]MIBGscintigraphy.Mostofthelesionsthatwerenegativeon[131I]MIBGscintigraphyandpositiveon[68Ga]DOTANOCPET/CTwereextra-adrenalPG.40
MIBG versus 18F-FDG
Firstofall,in1999,Shulkinet al. compared[123/131I]MIBGscintigraphywith[18F]FDGPETin29patientswithPheo.TheseauthorsfoundthatmostPheoac-cumulate[18F]FDGandthat[18F]FDGPETwasespe-ciallyusefulinthosepatientswhofailedtoconcen-trate[123/131I]MIBG.17AlsoMannet al. demonstratedthefeasibilityandusefulnessof[18F]FDGPETinthedetectionofPheo.22
In2006,Mamedeet al. evaluating5patientswith
In their prospective study in 52 patients withknownor suspectedPheoorPGL,Timmers et al. foundthatthesensitivityforlocalizingnon-metastat-icPGLwas81%for[18F]DOPAPETand78%for[123I]MIBG scintigraphy. For metastatic PGL, sensitivitywas45%for[18F]DOPAPETand57%for[123I]MIBGscintigraphy.31In2010,Fottneret al. compared[18F]DOPA PET with [123I]MIBG scintigraphy in 30 pa-tientswithknownorsuspectedPheoorPGL.Atotalof64lesionswerefoundwithbothfunctionalimag-ingmodalities. [18F]DOPAPETdetected62 lesions,whereasonly34lesionsweredetectedby[123I]MIBGscintigraphy. The overall sensitivity and specificityfor[18F]DOPAPETwere98%and100%andfor[123I]MIBGscintigraphy53and91%,respectively.Compa-rablesensitivitieswerefoundforadrenalandextra-adrenalabdominallesions(94vs.97%,respectively),whereas in thoracic/cervical lesions, thesensitivityfor[123I]MIBGscintigraphy(15%)wasinferiortothatof[18F]DOPAPET(100%).33
Rufini et al. compared [18F]DOPA PET/CT with[123I]MIBG scintigraphy in the re-staging of 12 pa-tientswithknownorsuspectedrecurrentPGL,dem-onstratingthesuperiorityof[18F]DOPAPET/CTover[123I]MIBG scintigraphy in assessing disease exten-sioninpatientswithrecurrentPGL.Perpatient-andper-lesionbased sensitivitieswere 100% and 98%,respectively, for [18F]DOPA PET/CT, and 75% and38%,respectively,for[123I]MIBGscintigraphy.Itwashoweversuggested that inpatientwith inoperabledisease, [123I]MIBGmaintainedauniquerole inal-lowing the selection of patients suitable for [131I]MIBGtherapy.37
Recently, King et al. demonstrated in their pro-spectivestudythat[18F]DOPAPETisthemosteffica-ciousfunctionalimagingmodalityinthelocalizationofSDHx-relatedheadandneckPGL,andmaybeapotentialfirst-line functional imagingagent for thelocalizationofthesetumors.Thesensitivityof[18F]DOPA PET in this setting was superior to that of[123I]MIBG scintigraphy (100% versus 31%, respec-tively).11
MIBG versus 68Ga-somatostatin analogues
Firstofall, in2007,Winet al. demonstratedthevalue of somatostatin receptor PET imaging inmalignant Pheo. These authors retrospectively re-viewed five patients with malignant Pheo, andfound that [68Ga]DOTATATEPET showedmore le-sionswithhigheruptakeandbetterresolutioncom-
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Lastly,Timmerset al. recentlycompared[18F]FDGPET/CTwith [123I]MIBGscintigraphyina largepa-tient population (N.=216)with suspected Pheo orPGL. For non-metastatic tumors, the sensitivity of[18F]FDGPET/CT(76.8%)wassimilartothatof[123I]MIBGscintigraphy(75%).Thespecificitywas90.2%for[18F]FDGPET/CTand91.8%for[123I]MIBGscin-tigraphy.On theotherhand, the sensitivity inde-tectingmetastaseswasgreaterfor[18F]FDGPET/CTthanfor[123I]MIBGscintigraphy(82.5%versus50%,respectively).41
Conclusions
The studies included in this systematic reviewwere quite heterogeneous for inclusion criteria,characteristics of patients evaluated and technicalaspectsofMIBGscintigraphyandPETimaging(Ta-blesI-III).Wecanhoweverconcludethat:
1) the diagnostic performance of [11C]HED PETimaging in patients with Pheo/PGL seems to besuperiortothatofMIBGscintigraphy.Majordraw-backsaboutthisPETradiopharmaceuticalinPheo/PGLarethelimitedavailabilityandthescarcelitera-tureevidence;
2) thediagnosticperformanceof [18F]DAPET inpatientswith Pheo/PGL is clearly superior to thatof MIBG scintigraphy. The use of this PET radio-pharmaceuticalishoweverlimitedbyitsavailability(usedasanexperimentaltraceratNHIonly);
metastatic Pheo demonstrated that [18F]FDG PETmayberecommended,inparticularwhen[123I]MIBGfailstolocalizelesionsseenonconventionalimag-ingstudies.21Timmerset al. reportedthat[18F]FDGPETisthepreferredfunctionalimagingmodalityforstaging and treatmentmonitoringof SDHB-relatedmetastaticPGL.Infact,evaluating30patientswithSDHB-relatedmetastaticPG,theseauthorsfoundaper patient-based sensitivity of 100% for [18F]FDGPETand80%for[123I]MIBGscintigraphy.24Inaddi-tion,Zelinka et al. showed that [18F]FDGPETwassuperior to [123/131I]MIBG scintigraphy in detect-ingbonemetastasesinpatientswithSDHB-relatedPGL.29IntheirretrospectivestudiesTaïebet al. alsodemonstratedthatmostpatientswithPheoorPGLmay concentrate [18F]FDG, and also [18F]FDG PETmightprovideadditional information compared to[131I]MIBG scintigraphy, especially in patients withmetastatic and abdominal PGL.27 Two Japanesestudiesalsoreportedthat[18F]FDGPETwassuperiorto[123I]MIBGscintigraphyindetectingmetastasesinpatientswithPheoorPGL.28,39Inparticular,Takanoet al. reportedthat[18F]FDGPETdemonstratedmet-astaticlesionsinall11patientsevaluated,while[123I]MIBGshowednometastaticlesionsin2patients.28
In their prospective study, King et al. recentlyfoundthat[18F]FDGPET/CTwassuperiorcomparedto[123I]MIBGscintigraphyindetectingSDHx-relatedhead and neck PGL, reporting a per lesion-basedsensitivityof77%for[18F]FDGPET/CTand31%for[123I]MIBGscintigraphy.11
Figure1.—Comparisonbetween[123I]MIBGscintigraphyand[18F]DOPAPETinapatientwitharightadrenalPheo.A)[123I]MIBGSPECT(axialimage)showingsymmetricfaintuptakeintheadrenalglands(falsenegativeresult);B)[18F]DOPAPET/CT(axialimage)showinghightraceruptakeintherightadrenalmass(redarrow)(truepositiveresult).
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Figure3.—Comparisonbetween[123I]MIBGscintigraphyand[18F]FDGPETinapatientwithmetastaticPGLandSDHBmutation.A)[123I]MIBGscintigraphyanterior(left)andposterior(right)wholebodyscanshowingnoareasofabnormalMIBGuptake;B)[18F]FDGmaximal-intensity-projectionPETimageshowingmultipleareasofabnormaluptakecorrespondingtoalocalrecurrenceintheleftadrenalregionaswellasboneandsofttissuemetastasesinsupra-andinfradiaphragmaticlymphnodesandintheliver.
Figure2.—Comparisonbetween[123I]MIBGscintigraphyand[18F]DOPAPETinapatientwithmetastaticPGL.A)[123I]MIBGscintigraphyanterior(left)andposterior(right)wholebodyscanshowingfaintMIBGuptakeinmultiplebonelesionsmainlylocatedinthevertebralcolumnandinpelvicboneswithlowtumor-to-backgroundratio,possiblyduetointerferingmedication;B)[18F]DOPAmaximal-intensity-projectionPETimageshowingagreaternumberoflesionsinalmostallbonesegments,whichareimagedwithhighcontrast.
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cakK.Detectionandtreatmentofpheochromocytomasandpar-agangliomas:currentstandingofMIBGscintigraphyandfutureroleofPETimaging.QJNuclMedMolImaging2008;52:419-29.
8. Taïeb D, Sebag F, Hubbard JG Mundler O, Henry JF, Conte-DevolxB.Does iodine-131meta-iodobenzylguanidine (MIBG)scintigraphyhaveanimpactonthemanagementofsporadicandfamilialphaeochromocytoma?ClinEndocrinol2004;61:102-8.
9. WisemanGA, PacakK,O’DorisioMSNeumannDR,WaxmanAD,MankoffDAet al. Usefulnessof123I-MIBGscintigraphyintheevaluationofpatientswithknownorsuspectedprimaryormetastaticpheochromocytomaorparaganglioma:resultsfromaprospectivemulticentertrial.JNuclMed2009;50:1448-54.
10. Ilias I,Yu J,Carrasquillo JA,ChenCC,EisenhoferG,WhatleyMet al. Superiorityof6-[18F]-fluorodopaminepositronemissiontomographyversus[131I]-metaiodobenzylguanidinescintigraphyinthelocalizationofmetastaticpheochromocytoma.JClinEn-docrinolMetab2003;88:4083-7.
11. KingKS,ChenCC,AlexopoulosDK,WhatleyMA,ReynoldsJC,PatronasNet al. FunctionalimagingofSDHx-relatedheadandneckparagangliomas:comparisonof18F-fluorodihydroxypheny-lalanine,18F-fluorodopamine,18F-fluoro-2-deoxy-D-glucosePET,123I-metaiodobenzylguanidine scintigraphy, and 111In-pentetre-otidescintigraphy.JClinEndocrinolMetab2011;96:2779-85.
12. TaïebD,NeumannH,RubelloD,Al-NahhasA,GuilletB,HindiéE.Modernnuclearimagingforparagangliomas:beyondSPECT.JNuclMed2012;53:264-74.
13. PacakK,EisenhoferG,GoldsteinDS.Functionalimagingofen-Functionalimagingofen-docrinetumors:roleofpositronemissiontomography.EndocrRev2004;25:568-80.
14. CuccurulloV,MansiL.Towardtailoredmedicine(andbeyond):thephaeochromocytomaandparagangliomamodel.EurJNuclMedMolImaging2012;39:1262-5.
15. LopciE,ChitiA,CastellaniMR,PepeG,AntunovicL,FantiSet al. Matchedpairsdosimetry: 124I/131Imetaiodobenzylguanidineand124I/131Iand86Y/90Yantibodies.EurJNuclMedMolImaging2011;38(Suppl1):S28-S40.
16. ShulkinBL,WielandDM,SchwaigerM,ThompsonNW,FrancisIR,HakaMSet al. PETscanningwithhydroxyephedrine:anap-proach to the localizationofpheochromocytoma. JNuclMed1992;33:1125-31.
17. Shulkin BL, Thompson NW, Shapiro B, Francis IR, Sisson JC.Pheochromocytomas: imaging with 2-[fluorine-18]fluoro-2-de-oxy-D-glucosePET.Radiology1999;212:35-4.
18. LeRestC,BomanjiJB,CostaDC,TownsendCE,VisvikisD,EllPJ.Functionalimagingofmalignantparagangliomasandcarci-noidtumours.EurJNuclMed2001;28:478-82.
19. HoegerleS,NitzscheE,AltehoeferC,GhanemN,ManzT,BrinkI et al. Pheochromocytomas: detection with 18F-DOPA wholebodyPET.Initialresults.Radiology2002;222:507-12.
20. FranziusC,HermannK,WeckesserM,KopkaK,JuergensKU,Vormoor J et al. Whole-body PET/CT with 11C-meta-hydrox-yephedrine in tumorsof thesympatheticnervoussystem: fea-sibilitystudyandcomparisonwith123I-MIBGSPECT/CT.JNuclMed2006;47:1635-42.
21. Mamede M, Carrasquillo JA, Chen CC, Del Corral P, WhatleyM,IliasIet al. Discordantlocalizationof2-[18F]-fluoro-2-deoxy-D-glucosein6-[18F]-fluorodopamine-and[123I]-metaiodobenzyl-guanidine-negative metastatic pheochromocytoma sites. NuclMedCommun2006;27:31-6.
22. MannGN,LinkJM,PhamP,PickettCA,ByrdDR,KinahanPEet al. [11C]metahydroxyephedrine and [18F]fluorodeoxyglucosepositronemissiontomographyimproveclinicaldecisionmakinginsuspectedpheochromocytoma.AnnSurgOncol2006;13:187-97.
23. KajiP,CarrasquilloJA,LinehanWM,ChenCC,EisenhoferG,Pin-toPAet al. Theroleof6-[18F]fluorodopaminepositronemissiontomography in the localizationofadrenalpheochromocytomaassociatedwithvonHippel-Lindausyndrome.EurJEndocrinol2007;156:483-7.
3)thediagnosticaccuracyof[18F]DOPAPETinpa-tientswithPheo/PGLisclearlysuperiorcomparedtothatofMIBGscintigraphy,notonlyindetectingPheo (Figure 1) but also in head and neck PGL,whereMIBGscintigraphyusually fails.Aclearad-vantageof[18F]DOPAover[123/131I]MIBGisthat[18F]DOPAPETcanbeperformedalsointhepresenceofdrugsthatinterferewithMIBGuptake(Figure2).
4)preliminarydataseemtosuggestthediagnos-tic superiorityof [68Ga]somatostatinanaloguesPEToverMIBGscintigraphyinpatientswithPheo/PGL;nevertheless,discordantfindingsusingtheseradio-pharmaceuticalsarealsoreported;
5) [18F]FDGPETisparticularlyuseful inpatientswith metastatic Pheo/PGL, mainly in SDHB muta-tioncarriers.Inthissetting,thediagnosticaccuracyof thismethod isclearly superior to thatofMIBGscintigraphy(Figure3);
6)despitethesuperiordiagnosticperformanceofPET with the different radiopharmaceuticals com-paredtoMIBGscintigraphyinpatientswithPheo/PGL,MIBGisstilltheworkhorseasanofficiallyap-provedandreimbursedagentwithcumulativeclini-calexperienceandalsomaintainsauniqueroleinallowing the selectionof patients suitable for 131I-MIBGtherapy.
7)furtherlargeprospectiveandmulticenterstud-ies comparing PET/CT performed with differentradiopharmaceuticalswithMIBGSPECT/CT inpa-tientswithPheo/PGLareneededaswellasacost-effectivenessanalysisabouttheuseofPETimagingandMIBGscintigraphyinthissetting.
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32. TimmersHJ,EisenhoferG,CarrasquilloJA,ChenCC,WhatleyM,LingAet al. Useof6-[18F]-fluorodopaminepositronemissionto-mography(PET)asfirst-lineinvestigationforthediagnosisand
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