Radiopharmaceu-cals in infec-on imaging 2017 Lectures/pretoria-1-intro-a...Inﬂammaon is a...

Radiopharmaceu-calsininfec-onimaging

AlbertoSignore,MD,PhDProfessorofNuclearMedicine,FacultyofMedicineand

Psychology,“Sapienza”UniversityofRome,Italy

HonoraryFullProfessoratDept.ofNuclearMedicineandMolecularImaging,UniversityMedicalCenterGroningen,The

Netherlands

ChairoftheInflammaHon/InfecHonCommiJeeoftheEuropeanAssociaHonofNuclearMedicine(EANM)

AMRin205010,000,000

1deathevery3seconds

ReviewonAn*microbialResistance2014

Tetanus60,000

Cholera110,000

Measles130,000

AMR700,000

Roadaccidents1,200,000

Diarrhoealdisease1,400,000

Diabetes1,500,000

Cancer8,200,000

MonselAetal.Anesthesiology2014;121:1099-121

Inflamma-onvsInfec-on

AcuteorchromicsepHcinflammaHon(infecHon)(mainlygranulocyte-mediated)

AcuteorchronicsterileinflammaHon(mainlymononuclearcell-mediated)

InflammaHonisaprotec-veresponseinvolvinghostcells,bloodvessels,andproteinsandothermediatorsthatisintendedtoeliminatetheiniHalcauseofcellinjury,aswellasthenecroHccellsandHssuesresulHngfromtheoriginalinsult,andtoiniHatetheprocessofrepair.

AlthoughinflammaHonhelpsclearinfecHonsandothernoxioussHmuliandiniHatesrepair,theinflammatoryreacHonandthesubsequentrepairprocesscanthemselvescauseconsiderableharm.

Acuteinflamma-onisrapidinonsetandofshortduraHon,lasHngfromafewminutestoaslongasafewdays,andischaracterizedbyfluidandplasmaproteinexuda-onandapredominantlyneutrophilicleukocyteaccumulaHon.

Chronicinflamma-onmaybemoreinsidious,isoflongerduraHon(daystoyears),andistypifiedbyinfluxoflymphocytesandmacrophageswithassociatedvascularprolifera-onandfibrosis(scarring).

AcuteinflammaHoncanbetriggeredbyInfec*ons(bacterial,viral,fungal,parasiHc),Traumaandvariousphysicalandchemical,Tissuenecrosisincludingischemiaandphysicalandchemicalinjury,Foreignbodies,andImmunereac*ons(alsocalledhypersensiHvityreacHons).

Pathophysiologyofinflamma-on

SignoreA.EJNMMIResearch2013;3:8SignoreA.EJNMMIResearch2013;3:8

Radiopharmaceu-calsforinfec-onimaging

SignoreA.etal.AnnNuclMed2011

RadiolabelledCiprofloxacin

AuleLaS.etal.ClinTransImaging2016;4:229-252

Othertestedan-bio-cs

AuleLaS.etal.ClinTransImaging2016;4:229-252

Imaginginfec-onsbytarge-ngbacteria

Radiolabelledprobe

Invitrospecificity

Animalmodel

Clinicalspecificity

Whatkindofanimal?

Howmanybacteria?

Whatkindofmodel?

Appropriatecontrol?

Comparisonofdifferentan--microbialagentsfortarge-ngbacterialinfec-ons

AuleLaS.etal.QJNMMI2017;[Epubaheadofprint]

DistribuHonprofileofradiopharmaceuHcalsatdifferentHmepointsintocagefluids(dispersedbacteria)

Datarepresent%ID/mlofHssuefluid,expressedasmeans±SEMofthreetofivemicepertesHnggroup.Significantdifferencesbetweeninfectedandcontrolfluidsareindicatedasfollow:*P<0.05,**P<0.005,***P<0.0005.

*

*

30 min 4 h 24 h0.0

0.5

1.01.5

2.0

2.5

3.0

3.5

4.0

%ID

/ml

99mTc-UBI

30 min 4 h 24 h0.0

0.1

0.2

0.3

0.4%

ID/m

l

99mTcN-CiproCS2

30 min 4 h 24 h0

1

2

3

4

5

%ID

/ml

99mTc-Ciprofloxacin

30 min 4 h 24 h0.0

0.2

0.4

0.6

1.0

1.5

2.0

2.5

%ID

/ml

111In-biotin111In-DTPA-bio-n

à  Sterilefluid

30 min 4 h 24 h0.0

0.5

1.01.5

2.0

2.5

3.0

3.5

4.0

%ID

/ml

99mTc-UBI

30 min 4 h 24 h0.0

0.1

0.2

0.3

0.4

%ID

/ml

99mTcN-CiproCS2

30 min 4 h 24 h0

1

2

3

4

5

%ID

/ml

99mTc-Ciprofloxacin

30 min 4 h 24 h0.0

0.2

0.4

0.6

1.0

1.5

2.0

2.5

%ID

/ml

111In-biotin

**

99mTc-UBI

*

**

*

99mTc-ciprofloxacin

30 min 4 h 24 h0.0

0.5

1.01.5

2.0

2.5

3.0

3.5

4.0

%ID

/ml

99mTc-UBI

30 min 4 h 24 h0.0

0.1

0.2

0.3

0.4

%ID

/ml

99mTcN-CiproCS2

30 min 4 h 24 h0

1

2

3

4

5

%ID

/ml

99mTc-Ciprofloxacin

30 min 4 h 24 h0.0

0.2

0.4

0.6

1.0

1.5

2.0

2.5

%ID

/ml

111In-biotinà  E.colifluidàS.aureusfluid

Datarepresent%ID/gofHssue,expressedasmeans±SEMofthreetofivemicepertesHnggroup.Significantdifferencesbetweeninfectedandcontrolcagesareindicatedasfollow:*P<0.05,**P<0.005,***P<0.0005.

Comparisonofdifferentan--microbialagentsfortarge-ngbacterialinfec-ons

DistribuHonprofileofradiopharmaceuHcalsatdifferentHmepointsintoexplantedcages(biofilm)

à  Sterilefluid à  E.colifluidàS.aureusfluid

99mTc-UBI 99mTc-ciprofloxacin 111In-DTPA-bio-n

AuleLaS.etal.QJNMMI2017;[Epubaheadofprint]

Conclusionsonbacteriaimaging•  Imagingbacteriaisadifficultandchallengingtask

•  Animalmodelsshouldbecarefullyselectedandstandardizedawellasbacteriastrains

•  Experimentaldesignshouldincludeinvitroandinvivostudieswithappropriatecontrols

•  CauHonshouldbetakenwhenusing[18F]FDGforimaginginfecHons

•  SinceWBCscinHgraphyshowedexcellentdiagnosHcaccuracyforimaginginfecHonsinhumans(>98%),bacterialimaginghasapotenHalassecondlineimagingtoolforidenHfyingthegermresponsibleforinfecHonandfollow-uptheefficacyoftailoredtherapies

Pros Cos Target Dosimetry Costperpa-ent

67Ga-citrate

150€

111In-WBC

300€

99mTc-WBC

300€

ScinHmun®

350€

Leukoscan®

350€

18F-FDG

1000€

Commerciallyavailableradiopharmaceu-calsforimaginginfec-on

Gallium-67

• CyclotronproducedbyprotonbombardmentofZn-68ina(p,n)reacHon• Pricedependsonhowmuchyouuse•  LongT1/2poordosimetryxxhr• AcHvitylimited150MBqintheUKwithanEDof18mSv•  Imagingon90,190,300keV• But5%yieldon394keVmeansneedmed/highcollimator

Gallium-67citrate

•  ActsasanalogueofFe,carriedonTransferrin/lactoferrin,willfollowIron•  Theseareacutephaseproteins•  CytochromeP450needsFe•  Sodomanybacteria(havereceptorsforhumanTF/LF)•  SlowlocalisaHonatsiteofinfecHon/inflammaHonandsometumours•  Inbloodmainlyproteinboundaserabout6hoursbeforethismaycirculateasfreeion•  First24hoursexcreHonofnon-boundfracHonviakidneys,thenexcretedasproteinboundfracHonintoileum/caecum

Characteris-csof67Ga-citrate

• ColonicandbonemarrowacHvityvariable• BreastacHvitycanoccurinpreg/lact/leutphase/HRT• WillbeverysensiHveformostinfecHonincludingpneumocysHsandTB• Problemwithimagingascountscanbelowinperiphery.SPECTdifficultbutpossible•  Imagingoutto7dayspossiblebutcountsreduced•  SomeuptakeinmetabolicallyacHvebonesforexamplerecentfractures• MaybebestforvertebralinfecHons

67Ga-citrateindica-ons

• MostcommonindicaHonsfor67Ga-citratesupersededbynewertests

• However,inspecialcases67Gamayhavearole•  Intheneutropenicwhen[18F]FDGnotpossible•  InvertebralosteomyeliHswhenwhitecelllabellingtechniquesareatadisadvantage

•  InsomechronicinfecHonssuchastuberculosis•  Inassessingsarcoid.

Slide16

Advantagesof67Ga-citrate•  Doesnotneedcelllabelling•  UsefulifpaHentisneutropenic•  UsefulifinfecHondoesnotlocaliselabelledleucocytessuchaschronicTBandpneumocys2scariniiinfecHons,spondylodisciHs

•  Usefulifbloodinfected(HIV,HCV,HBV)•  AvailableasstockitemandrelaHvelycheap•  Canbeorderedinadvanceifsufficientuseaslonghalflifeaidsstorageoverafewdays

Slide17

Disadvantagesof67Ga-citrate•  PoorlyspecificforinfecHon,canimageinflammaHonandtumors•  NotunivocalinterpretaHoncriteriaforimages•  Longhalflifeandpoordosimetry(nouseinchildren)•  CannotbeusedinpaHentstakingironbinders

67Ga-citratedosimetry

Organ ReferencedosemGy/MBq

Largebowel 0.2432

RedMarrow 0.1568

Spleen 0.1432

Liver 0.1243

Bone 0.1189

Smallbowel 0.0973

Ovaries/testes 0.0703

Wholebody 0.0703

SourceJNM1973;14:755-6ED0.012mSv/MBqformaximum150MBq=18mSv


67Ga-citrateNolabelling,cheap,imagebacteriaandvertebralOM

Longhalf-life,poorimages,poorlyspecific,highradiaHon

Transferrin,bacteria,

acHvatedcells(Kreb’scycle)

18mSv(largebowel) 150€

111In-WBC

99mTc-WBC

ScinHmun®

Leukoscan®

18F-FDG


LabelledWBCs• RadiopharmaceuHcalsusedforWBClabelling•  In-111oxine•  In-111tropolone•  Tc-99mexemetazime(HMPAOhydroxymethylpropyleneamineoxime)

• AllcomplexesarelipophilicaminesthatenterleucocytebydiffusionandaretrappedinsidecellaserreducHon(glutathione)•  Leucocytesneedtoremainalive,notacHvatedandsterile•  LabellingoriginallydescribedinplasmabutcanalsobedoneinsalineorPBS(compulsoryforoxine)

Whichradiopharmaceu-calforWBClabelling

•  In-111WBCs• Max90MBq• Uptakeinliver,spleenandBM• NobileexcreHon• Poorcountsinperiphery• Mediumenergycollimator•  SPECT-CTnotideal

•  Tc-99mHMPAOWBCs• Max555MBq• Highliverandspleenuptake• BileexcreHonandbowelacHvityaser3-4hours•  Lowenergycollimator• GoodforSPECT/CTbutlowcountrateat20h

Slide21

•  AccumulaHonininfecHonsisadynamicprocess•  DualHme-pointimaging(3-4and20-24hoursaserinjecHon)isnecessary;whenpossibleacquirealsoearlyphase(30min)images

RadiolabelledWBCforinfec-onimaging

HowtoacquireWBCandan--Gimages?

Signare A, Quintero AM. Diagnostic imaging of infections &inflammatory diseases: a multidisciplinary approach J. Wiley Pbl. 2013

Acquisi-on-me-tablecorrectedforisotopedecay

Criteriaforposi-vity:-AnyuptakewithincreaseofacHvitywithHme-AnyuptakewithincreaseofsizewithHme

Sequen-alWBCimagingfordiagnosisofinfec-on

Definespecifickine-cpaXernsofradiopharmaceu-cals

99mTc-HMPAO-leukocyte scintigraphy in a patient with bilateral knee prostheses and suspected left knee prosthesis infection. Quantitative analysis: SRearly = 64.7; RRearly = 61.9; SRlate = 28.1; RRlate = 13.7; T/Bearly = 1.05 T/Blate = 2.05

Qualita-veorsemi-quan-ta-veanalysis?

Pelosi E. et al. J Nuc Med 2004;45:438-444

Infec-on

Noninfec-on

111In-WBC 99mTc-nanocolloid

CombinedbonemarrowandWBCimagingfordiagnosisinfecHon

Combinedbone-marrowscantoiden-fyac-vedisplacedbonemarrow

IsitanybeXertouseSPECT/CT?

L.Filippi et al. J Nuc Med 2006

111In-oxine-WBCdosimetry


Spleen 0.703

Liver 0.103

RedMarrow 0.0703

Bone 0.00197

Testes 0.0005

Ovary 0.0102

Wholebody 0.0168

SourceMedi-physicsED0.45mSv/MBqformaximum90MBq=9mSv


Spleen 0.0755

Kidneys 0.0184

Bladderwall 0.0177

GallBladder 0.0148

Lungs 0.0141

Colon 0.0105

Pancreas 0.0098

Wholebody 0.0038

SourceJNM2008;49:1380-1385ED0.0137mSv/MBqformaximum400MBq=5.56mSv

99mTc-HMPAO-WBCdosimetry







111In-WBCGoodfor

inflammatoryboweldiseases

SterilebloodmanipulaHon,poorimaging

Mainlyneutrophils

9mSv(spleen) 300€

99mTc-WBCGoodforboneandjointinfecHons,goodSPECTimages

SterilebloodmanipulaHon,

bowelexcreHon,notforspondylo

Mainlyeosinophils

5.6mSv(spleen) 300€

ScinHmun®

Leukoscan®

18F-FDG


InvitroWBClabelingwithdisposablesterilecloseddevice

InvitroWBClabelingwithLeukokit®

1 2

3

InvitroWBClabelingwithLeukokit®







111In-WBCGoodfor



Mainlyneutrophils

9mSv(spleen) 300€




Mainlyeosinophils


ScinHmun®

Leukoscan®

18F-FDG


An-bodies• AnHbodiesarecomplexproteinsmadeupoftwolongchainscalledtheheavychainsandtwoshorterchainsthelightchains,bothconnectedbysulphidebridges•  SimplestformIgGwithamolecularweightof150kDa•  TheCterminalsofthetwoheavychainshaveasinglecharacterisHcineachspecies(Fc=constantfactor)•  TheNterminalsoftwolightandtwoheavychainsvarydependingontheanHgentheyrecognisethe(Fab=anHgen-bindingfactor)•  IneachindividualtheFcwillbeconstant(foreachIgtype)buttherewillbeavarietyofFabporHons

Slide35

Monoclonalan-bodiesandHAMAs

•  IfamonoclonalanHbodyisraisedagainstahumancelllineinamousethatanHbodycanbeinjectedbackintohuman•  FabidenHfiestheanHgenandbinds• HowevermouseFccanitselfbecomeananHgensohumananHbodiescanberaisedagainstit•  ThereforebyinjecHngamousederivedanHbodyitispossibletoinduceahumananHmouseanHbody(HAMA)• HAMAscanbindtooriginalanHbodiesandformimmuno-complexesthatmayprecipitateinkidneys

Slide36

Fromcompletean-bodiestoFab‘fragments

Papain

Fab Fc

CH2CH3

VL

CLVH

CH1

VL

CLVH

CH1

SchemaHcrepresentaHonofenzymaHccleavageofa

completeIgGintoFab’fragments(accordingGemsa,Kaldenand

Resch;Immunologie,P.17,ThiemeVerlag1997,4th

ediHon)

IgG 150 kD

Fab‘ 50 kD 99mTc / 111In

light chain

heavy chain

99mTc-an--granulocytemAb

•  LicenceforosteomyeliHs• CouldbeusedinanysituaHonwherelabelledwhitecellsused• Howevernotgoodfor:

•  Inflammatoryboweldisease(crossreacHvitywithCEA)•  VertebralosteomyeliHs•  NeutropenicpaHents

• Only2typesavailable,bothlabelledwithTc-99m

Slide38

99mTc-besilesomab(Scin-mun®)•  DevelopedmainlyinGermany•  BW250/183wholemouseIgGdevelopedbyLocheretal.atPaulShirerinsHtutenearZurich• WholemouseIgGdirectedagainstCD66(NCA-95)whichisaglycoproteinonsurfaceofhumangranulocyte•  UsedprimarilyinboneandjointinfecHons•  Rapiduptakeintobonemarrow,somerenalandbladderacHvity,laterbowelmaybeseen•  RapiduptakeininfecHons.LateimagesnecessarytoshowincreasedaccumulaHonatinfecHonsites•  TheoreHcalissuewithHAMAespeciallyifpaHenthasbeenexposedtomouseproteinsbefore

Slide39

• DevelopedbyGoldenburginUSA•  Fab’fragmentofamouseanHbodytargetedtoNCA90• NorealriskofHAMA.Canbegivenmorethanonce• HighbackgroundandhighlevelsofacHvityintheblood,urinarysystemandgut•  LicencedbyEMEAforperipheralinfecHonsonly• Becauseofhighbloodpooldifficulttoimagechest,abdomenandpelvis•  SPECTmayhelp•  SomedoubtthereisspecifictargeHng

Slide40

99mTc-sulesomab(Leukoscan®)

HAMAkit(MileniaQuickLine®)•  Beforeopeningthevialsbringthetestunitandchasebuffertoroom

temperature(18-28°C).•  Usethetestunitimmediatelyaseropening.•  Donotstoreatroomtemperature.

99mTc-IgG

99mTc-Fab`

99mTc-an--granulocytemAbSerumclearenceofIgGandFab`

99mTc-F(ab`)2

Note:TheFab’clearsmuchfasterthanIgGthusimagingbeyond4-6hourscanbeavoided 99mTc-F(ab`)2

Behr:CancerRes.1995

Gratz:EurJNuclMed.1998

99mTc-an--granulocytemAbSerumclearenceofIgGandFab`

Behr:CancerRes.1995Gratz:EurJNucMed.1998Gratz:QJNuclMed.2015

IgG Fab’

99mTc-an--granulocytemAbOsteomieliHstargeHng

Gratz:EurJNucMed.1998Gratz:QJNuclMed.2015

CorrelaHonbetweenT/BraHosof99mTc-sulesomaband99mTc-HSA(6h)andbetweenT/BraHosof111In-leukocytes(22h)and

99mTc-sulesomaband99mTc-HSA(6h).

Themechanismofac-onof99mTc-sulesomabremainsunclear,althoughitisnotrelatedto

intravascularbindingtocircula-nggranulocytes

SJ.Skehanetal.JNM44:11-18;2003

0

1

2

3

4

0 4 8 12 16 20

T/Bk

g(Sulesom

ab)

T/Bkg(111In-leukocytes)

o=HSA

Themechanismofac-onof99mTc-sulesomabremainsunclear,althoughithasbeensuggestedtoacquireimagesatboth4hand24hpostinjec-on

D.Rubelloetal.NucMedCommun25:39-47;2004

Itwouldperhapsbehelpful,here,todrawadisHncHonbetweentwodifferentdefiniHonsofspecificity:

- Radiopharmaceu-calspecificityistodowithwhetheranagentlocalizesinalesionthroughawell-definedphysiologicprocessforwhichitwasdesigned.

- Clinicalspecificityisameasureofthenumberoffalse-posiHveresults;

Thereappearstobeawidelyheldview,thatifaccumulaHon(i.e.,target-to-backgroundraHo)ofaradiopharmaceuHcalforinfecHonimagingconHnuestoincreaseover24h,theagentmustbespecificbythesecondofthesecriteria.

Labeledleukocytesarespecificonboth,butaradiolabeledprotein,suchaspolyclonalIgG,onlyonthefirst.ThatdoesnotmeantosaythatIgGwouldnotshowincreasinglocalizaHonoverHme.Itclearlydoes,andmoreover,99mTcdetachedfromtheproteinmayberetainedinHssue.Therefore,thefactthatanagent,including99mTc-sulesomab(LeukoScan;Immunomedics,Inc.),givesbeJerimagesat24hthrowsnolightonitsmechanismofaccumulaHon,whichcouldsHllbe“nonspecific.”

Themechanismofac-onof99mTc-sulesomabremainsunclear,despiteitsaccumula-oninaffected-ssuesmayincreasefrom4hto24hpostinjec-on

AM.Petersetal.JNM46:382-383;2005

InvivoWBClabellingwithan--granulocyteIgG(Besilesomab,Scin-mun®):lateimages

Bonescan Scin-munscan

Poolphase Earlyscan(4h)

Bonephase Latescan(20h)

27/11/17 Sousa R. et al. Nucl Med Commun 32:834;2011

Infected

Combined6himageswithcolloidscanfordisplacedbonemarrowidenHficaHon

InvivoWBClabellingwithan--granulocyteFab’an--NCA90(Leukoscan®)

Non-infected


Spleen 0.0271

Bonemarrow 0.0242

Kidney 0.0210

Bone 0.0177

Lungs 0.0125

Liver 0.0100

Adrenals 0.00759

Wholebody 0.00446

SourceIBAED0.00863mGy/MBqformaximum740MBq=6.83mSv

99mTc-besilesomab(Scin-mun®)dosimetry


Kidneys 0.0444

Bladderwall 0.0215

Spleen 0.0157

Heartwall 0.0118

Lungs 0.0100

Liver 0.0090

Bone 0.0080

Wholebody 0.00103

SourceImmunomedicsED0.00800mSv/MBqformaximum740MBq=5.92mSv

99mTc-sulesomab(Leukoscan®)dosimetry







111In-WBCGoodfor



Mainlyneutrophils

9mSv(spleen) 300€




Mainlyeosinophils


ScinHmun®BehaveslikeWBC,easytouse,bindstogranulocytes

HighBMuptake,HAMAs

CirculaHngandinfiltraHnggranulocytes


Leukoscan®NoHAMAs,imagesat1and6h,low

BMuptake

Notsurespecificity,

expertreading

Granulocytes,edema

5.9mSv(kidney) 350€

18F-FDG

1000€


[18F]FDG:aglucoseanalog

Fluoro-deoxyglucoseGlucose

•  CyclotronproducHonbyprotonbombardmentofenriched[15O]waterandisboundtomannosetriflateunderstereospecificSN2reacHoncondiHons-  electrophilicfluorinaHonwith18F2-  "nucleophilicsynthesis"

•  T1/2=110min(at70%)

•  F-18decaysbyβ+emission:249.8keV,96.73%perdisintegraHon

K3

K4

Hexokinase

Glucose-6-phosphatase

[18F]FDG-1-P

Glycogen

18F-FRU-6-P

Glycolysis

[18F]FDG-6-phospho-glucono-lactone

HMP

shunt

Blood

K1

K2[18F]FDG-6P[18F]FDG

OverexpressionofglucosetransportersGLUT-1andGLUT-3

[18F]FDG

[18F]FDG:uptakeandreten-on

[18F]FDGparallelsglucosemetabolism

•  Tri-exponenHaldecaycurveinarterialblood•  EarlyeliminaHonphase=0.2-0.3minutes

•  <33mins,about3.9%oftheinjecteddosecanbemeasuredintheurine

•  <2hrspost-administraHonabout20%oftheinjecteddosefoundinthebladder

•  [18F]FDGuptakeisrelatedtotheglycolyHcacHvityofcellsresponsiblefortheinflammatoryresponse

•  CellsinvolvedininfecHon/inflammaHon:-  acHvatedlymphocytes,neutrophils,macrophages,fibroblasts,osteoblasts,

acHvatedendothelialcells,bonemarrowcells

•  EnhancedglucoseconsumpHoncanalsobetheresultofastressreacHoninresponsetocellulardamage

FDGimagingofinfec-on:Pros&Cons

Advantages•  F-18:goodphysicalproperHes•  FDG:goodtracerkineHcs•  PET:highspaHal&contrast

resoluHongoodimagequality•  CT:anatomicinformaHon•  StudyduraHon:1.5–2h•  ShortphysicalT1/2:lower

radiaHon•  Nobloodhandling

Limita-ons•  Nonspecificuptake:

•  Physiologic•  Malignancies•  ForeignbodyreacHon

•  AvailabilityandwaiHnglist•  Costand[lackof]

reimbursement

[18F]FDG:biodistribu-onanddosimetry







111In-WBCGoodfor



Mainlyneutrophils

9mSv(spleen) 300€




Mainlyeosinophils


ScinHmun®BehaveslikeWBC,easytouse,bindstogranulocytes

HighBMuptake,HAMAs

CirculaHngandinfiltraHnggranulocytes


Leukoscan®NoHAMAs,imagesat1and6h,low

BMuptake

Notsurespecificity,

expertreading

Granulocytes,oedema

5.9mSv(kidney) 350€

18F-FDGNobloodhandling,

highqualityimages

Highcost,notreimbursed,non

specific

SeveralmetabolicallyacHvecells

Upto12mSv(bladder) 1000€


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