Evidence-based Positron Emission Tomography

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Evidence-basedPositron EmissionTomographySummary of RecentMeta-analyses on PETGiorgio TregliaLuca GiovanellaEditors123

Evidence-based Positron EmissionTomography

Giorgio Treglia Luca GiovanellaEditorsEvidence-basedPositron EmissionTomographySummary of Recent Meta-analyseson PET

EditorsGiorgio TregliaClinic of Nuclear Medicineand Molecular Imaging, ImagingInstitute of Southern SwitzerlandEnte Ospedaliero CantonaleBellinzonaSwitzerlandLuca GiovanellaClinic of Nuclear Medicineand Molecular Imaging, ImagingInstitute of Southern SwitzerlandEnte Ospedaliero CantonaleBellinzonaSwitzerlandThis book is an open access publication.ISBN 978-3-030-47700-4    ISBN -47701-1(eBook) The Editor(s) (if applicable) and The Author(s) 2020Open Access This book is licensed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits use, sharing,adaptation, distribution and reproduction in any medium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the Creative Commonslicense and indicate if changes were made.The images or other third party material in this book are included in the book's CreativeCommons license, unless indicated otherwise in a credit line to the material. If material is notincluded in the book's Creative Commons license and your intended use is not permitted bystatutory regulation or exceeds the permitted use, you will need to obtain permission directlyfrom the copyright holder.The use of general descriptive names, registered names, trademarks, service marks, etc. in thispublication does not imply, even in the absence of a specific statement, that such names areexempt from the relevant protective laws and regulations and therefore free for general use.The publisher, the authors, and the editors are safe to assume that the advice and information inthis book are believed to be true and accurate at the date of publication. Neither the publisher northe authors or the editors give a warranty, expressed or implied, with respect to the materialcontained herein or for any errors or omissions that may have been made. The publisher remainsneutral with regard to jurisdictional claims in published maps and institutional affiliations.This Springer imprint is published by the registered company Springer Nature Switzerland AGThe registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

PrefacePositron emission tomography (PET), by using different radiopharmaceuticals evaluating different metabolic pathways or receptor expression, is afunctional imaging method widely available worldwide.In particular, hybrid tomographs as positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magneticresonance imaging (PET/MRI) combining morphological and functionalinformation are currently used in the clinical practice.Even if a large amount of literature is available about PET, the number ofevidence-based articles on this imaging method, such as systematic reviewsand meta-analyses, is relatively limited.A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analysis can be performed when there are multiple scientific studies addressing the same question, with each individualstudy reporting measurements that are expected to have some degree of error.The aim then is to use approaches from statistics to derive a pooled estimateclosest to the unknown common truth. Existing methods for meta-analysisyield a weighted average from the results of the individual studies. In additionto provide an estimate of the unknown common truth, meta-analysis has thecapacity to identify sources of disagreement among the different study results,or other interesting relationships that may come to light in the context ofmultiple studies. A key benefit of this approach is the aggregation of information leading to a higher statistical power and more robust point estimate thanis possible from the measure derived from any individual study.This unique evidence-based book summarizes the findings or recent meta- analyses on the use of PET for different clinical indications. These meta- analyses on PET have been selected by the editors after a systematic literaturesearch performed by using PubMed databases (last search: January 2019).Meta-analytic articles published from 2012 to the date of the last literaturesearch were selected.About the structure of this book, after a section introducing PET and meta- analyses, respectively, several sections describe the results of meta-analyseson PET for different indications including the following medical fields:oncology, cardiology, neurology, infectious and inflammatory diseases.The different chapters are written by researchers who are both expert inPET and familiar with meta-analytic methodology.This book provides evidence-based information on PET, which can bevery useful for clinicians of different specialties and for internationalv

Prefacevis cientific societies. In particular, the evidence-based information providedby this book could help international scientific societies and national regulatory bodies on healthcare in approving the use of PET for several emergingclinical indications.Furthermore, the updated information provided by this book could helpworldwide clinicians of different specialties in prescribing PET with severalradiotracers for different clinical indications.Bellinzona and Lugano, Switzerland Zurich, Switzerland Giorgio TregliaLuca Giovanella

ContentsPart I  Introduction1 Introduction to Different PET Radiopharmaceuticalsand Hybrid Modalities (PET/CT and PET/MRI)   3Luca Giovanella, Lisa Milan, and Arnoldo Piccardo2 A Practical Guideline on Diagnostic and PrognosticMeta-Analyses 17Ramin Sadeghi and Giorgio TregliaPart II  Evidence-Based PET in Oncology3 Evidence-Based PET for Brain Tumours 25Giorgio Treglia and Barbara Muoio4 Evidence-Based PET for Head and Neck Tumours 35Gaetano Paone5 Evidence-Based PET for Thoracic Tumours 41Filippo Lococo, Alfredo Cesario, Stefano Margaritora,and Giorgio Treglia6 Evidence-Based PET for Breast Cancer 53Giorgio Treglia7 Evidence-Based PET for Abdominal and Pelvic Tumours 59Salvatore Annunziata, Daniele Antonio Pizzuto,and Federica Galiandro8 Evidence-Based PET for Cutaneous, Musculoskeletaland Unknown Primary Tumours 73Luisa Knappe and Gaetano Paone9 Evidence-Based PET for Haematological Tumours 79Francesco Bertagna, Raffaele Giubbini,and Domenico Albano10 Evidence-Based PET for Endocrine Tumoursand Disorders 89Alexander Stephan Kroiss and Giorgio Tregliavii

viiiPart III  Evidence-Based PET in Cardiology11 Evidence-Based PET for Cardiac Diseases 99Christel H. Kamani, Marie-Madeleine Meyer,Sarah Boughdad, Nathalie Testart, Marie Nicod Lalonde,Gilles Allenbach, Mario Jreige, Niklaus Schaefer,Giorgio Treglia, and John O. PriorPart IV  Evidence-Based PET in Infection and Inflammation12 Evidence-Based PET for Infectiousand Inflammatory Diseases 111Giorgio Treglia and Barbara MuoioPart V  Evidence-Based PET in Neurology13 Evidence-Based PET for Neurological Diseases 125Alberto Miceli, Selene Capitanio, Maria Isabella Donegani,Stefano Raffa, Anna Borra, Matteo Bauckneht,and Silvia MorbelliPart VI  Miscellaneous14 Meta-Analyses on Technical Aspects of PET 139Luca CerianiContents

Part IIntroduction

1Introduction to Different PETRadiopharmaceuticals and HybridModalities (PET/CT and PET/MRI)Luca Giovanella, Lisa Milan, and Arnoldo Piccardo1.1 Physical Principlesof Positron EmissionTomography and HybridModalitiesPositron Emission Tomography (PET) is animaging technique performed by using positronemitting radiotracers. Positron decay occurs withneutron-poor radionuclides and consists in theconversion of a proton into a neutron with thesimultaneous emission of a positron (β ) and aL. Giovanella (*)Clinic of Nuclear Medicine and Molecular Imaging,Imaging Institute of Southern Switzerland,Ente Ospedaliero Cantonale, Bellinzona, SwitzerlandLaboratory of Radiomics and Predictive Imaging,Imaging Institute of Southern Switzerland,Ente Ospedaliero Cantonale, Bellinzona, SwitzerlandClinic of Nuclear Medicine, University Hospitaland University of Zurich, Zurich, Switzerlande-mail: luca.giovanella@eoc.chL. MilanClinic of Nuclear Medicine and Molecular Imaging,Imaging Institute of Southern Switzerland,Ente Ospedaliero Cantonale, Bellinzona, SwitzerlandLaboratory of Radiomics and Predictive Imaging,Imaging Institute of Southern Switzerland,Ente Ospedaliero Cantonale, Bellinzona, SwitzerlandA. PiccardoDivision of Nuclear Medicine, Ente Ospedaliero“Ospedali Galliera”, Genoa, Italyneutrino (ν). The positron has a very short lifetime, and after the annihilation with an electronsimultaneously produces two high-energy photons (E 511 keV) in approximately oppositedirections that are detected by an imaging camera. The PET scanning is based on the so-calledannihilation coincidence detection (ACD) of the511 keV γ-rays after the annihilation.Tomographic images are formed collecting datafrom many angles around the patient by scintillating crystals optically coupled to a photondetectors used to localize the position of theinteraction and the amount of absorbed energy inthe crystals (Table 1.1) [1].Table 1.1 Properties of PET scintillator crystalsEffective atomicnumber (Z)μ (cm 1)Index ofrefractionDensity (g/cm3)Photon yield(per kVp)Peakwavelength(nm)Decay timeconstant (ns)Energyresolution (% at511 keV)HygroscopicNaI(Tl) BGO LSO507366GSO 67387.1387.30254104807.406.7120–30 12–1542043042023030040417.8%20% 10.1% 9.5% 20%YesNo The Author(s) 2020G. Treglia, L. Giovanella (eds.), Evidence-based Positron Emission -1 1No65NoNo3

L. Giovanella et al.4Table 1.2 The PET scanner performance and the intrinsic PET limitationsSpatialresolutionSensitivityNoise- equivalentcount rateContrastDefinitionThe minimum distancebetween two points in animage that can bedetected by a scannerIntrinsic limitationPositron range: Error occurs in the localization of the true position of thepositron emission resulting in the degradation of the spatial resolutionNon-collinearity: The two 511 keV photons are not emitted at exactlyopposite directions: This deviation can reach a value of 0.25 at maximumdetector size and its intrinsic resolution: resolution is better in the centre ofthe FOV than at the edgeGeometric efficiency: the fraction of emitted radiation that hits the detectorNumber of counts perunit time detected by the and it depends on the source to detector distance, on the diameter of the ringand on the number of detectors in each ringsystem for a unitaryIntrinsic efficiency: the fraction of radiation that reaches the detector and isactivityacquired. It depends on the scintillation decay time and the stopping powerof the detectorParameter used to define Takes into account the effects introduced by scatter and randomthe noise and to compare coincidencesthe PET performanceScatter, random and out-of-FOV radiationDifference in countsbetween an area ofinterest and itssurroundingsThe key properties that characterize the PETscanner performances are the spatial resolution,the sensitivity, the Noise-Equivalent CountRate (NECR) and the contrast [2]. The projection data acquired in the form of sinograms areaffected by a number of factors that contributeto the degradation of the final images and henceto the PET scanner performances, as reported inTable 1.2.Two classes of reconstruction techniques exist:the analytical and the iterative methods [3]. Themost used analytical method is the backprojection. To compensate the blurring, a filter is appliedto the projections before they are back- projectedonto the image [i.e. filtered backprojection(FBP)]. In modern scanners, the image reconstruction algorithms are based on iterative methods, which approach the true image by means ofsuccessive estimations, in order to converge to animage that best represents the original object.These algorithms are known as expectation maximization (EM) and Ordered Subset ExpectationMaximization (OSEM) algorithm [4].1.2 ybrid Scanners: PET/CTHand PET/MRICombined PET/CT systems were commerciallyavailable from 2001 and in a very short time thededicated PET scanner was completely replacedby hybrid PET/CT. The ability of hybrid PET/CTsystems to accurately identify the anatomic location of diseases and to provide attenuation- corrected images are the main causes of theirrapid success and diffusion [5]. Modern clinicalPET/CT consists in a high-performance PETscanner in-line with a high-performance CT scanner arranged in sequential gantries. The scannertable moves along the gantry axis in order to subsequently acquire CT and then PET data. A software integrated in the system has to check if thepatient bed undergoes some deflections during thetranslation [6]. Images of tissue attenuation fromthe CT scan are used to derive the PET attenuation correction factors. The latter depends on theenergy of the photons: since CT X-rays and PETγ-rays have an energy of 70 keV and 511 keV,

1Introduction to Different PET Radiopharmaceuticals and Hybrid Modalities (PET/CT and PET/MRI)5Table 1.3 The characteristics of the three commercially available PET/MRI scannersPET/MR technologyPETScintillatorCrystal size (mm)Crystal numberPhotodetectorTOFEnergy resolution (%)Energy window (keV)Time resolution (ns)Coincidence window (ns)Transaxial FOV (cm)Axial FOVSensitivity (kcps/MBq)Scatter fraction (%)Peak NECR (kcps @ kBq/mL)MRField strength (T)Bore (cm)FOV (cm3)Gradient mT/mSlew rate (T/m)/sSiemens biographmMRIntegratedPhilips ingenuitySequentialGE SignaIntegratedLSO4 4 2028,672APDNo14.5430–6102.935.8659.4 cm25.8 cm15.037.9184@ 23.1LYSO4 4 3.7LBS4 5.3 2520,160SiPMYes10.5425–6500.394.5760 cm25 cm22.243.4218@17.736050 50 504520036050 50 454010036050 50 5044200respectively, the attenuation correction factorobtained from CT must be scaled to the 511 keVphotons applying a scaling factor defined by theratio of the μ of the 511 keV photons to that of the70 keV X-rays in a given tissue [1].PET/MRI is a multi-modality technologycombining the functional information of PETwith the soft-tissue contrast of MRI. Actually,two approaches are implemented in the commercial PET/MRI scanners: sequential PET/MRI[7–9]. The characteristics of the three commercial PET/MRI scanners are summarized inTable Positron euticals are radiolabelled molecules consisting in a molecular structure and aradioactive nuclide. The first one defines thepharmacokinetics and dynamics within theorganism, while the latter is responsible for adetectable signal and for the consequent imagevisualization [10]. To maintain the stability ofthese two components, a linker may be necessary.The most important PET nuclides and their physical characteristics are summarized below:–– Carbon-11 (11C) has a physical half-life ofabout 20 min and decays by β emission(99.75%) and by electron capture (0.25%) tothe ground state of the stable nuclide Boron- 11(11B). β average energy is 386 keV, corresponding to a mean range in water of 1.3 mm.11C can be produced by different nuclear reactions; however, the main production mode istargeting Nitrogen-14 (14N) with cyclotronaccelerated protons: 14N(p,α)14C.–– Fluorine-18 (18F) has a physical half-life ofabout 110 min and decays by β emission(96.86%) and electron capture (3.14%)directly to the ground state of the stable

L. Giovanella et al.6nuclide Oxygen-18 (18O). β average energyis 250 keV, corresponding to a mean range inwater of 0.6 mm. 18F can be produced by different nuclear reactions; however, the mainproduction mode is targeting 8F.–– Gallium-68 (68Ga) has a physical half-life ofabout 67.8 min and decays by β emission(88.88%) and by electron capture (11.11%)into 68Zn. β average energy is 830 keV, corresponding to a mean range in water of3.6 mm. 18Ga can be produced by differentnuclear reactions; however, the main production mode is using a Germanium-68 (68Ge)68Ga generator.–– Iodine-124 (124I) has a physical half-life ofabout 4.2 days and decays by β emission(23%) and by electron capture (77%) to theexcited level and the ground state ofTellurium- 124 (124Te). β average energy is836 keV, corresponding to a mean range inwater of 3.4 mm. 124I can be produced bydifferent nuclear reactions; however,124Te(p,n) reaction gives the purest form of124I.–– Copper-64 (64Cu) has a physical half-life ofabout 12.7 h and decays by β emission (38%)to Zinc-64 (64Zn) and by β emission (17.4%)or electron capture (44.6%) to the excitedlevel and the ground state of Nickel-64 (64Ni).β average energy is 278 keV, correspondingto a mean range in water of 0.7 mm. The mainCu production modes are the following:63Cu(n,γ)64Cu, 65Cu(n,2n)64Cu, 64Zn(n,p)64Cu,64Zn (d,2p)64Cu.64The wide and feasible availability of positronemitters radionuclides is a prerequisite for successful application on a routine basis. Fluorine-18and Gallium-68 are the most used in a clinicalsetting, so far. Due to its versatility,18F-Fluorodeoxyglucose (FDG), namely a radiolabelled analogue of glucose, is the by far mostwidely used PET radiopharmaceutical worldwide. FDG is very useful to detect malignanttumours characterized by increased glucosemetabolism. However, FDG remains a non- specific tracer and its uptake is also been observedin many benign conditions, such as infective andinflammatory processes. Therefore, over the lastdecade, there is a growing interest in researchingand using new radiopharmaceuticals, such asradiolabelled amino acids, nucleoside derivatives, choline derivatives, nitroimidazole derivatives and peptides, able to carefully target specificbiomarkers. These new generation radiopharmaceuticals allow the analysis of several molecularpathways in tumour biology including metabolism, proliferation, oxygen delivery and proteinsynthesis as well as receptor and gene expression(Tables 1.4, 1.5 and 1.6). Some examples of PETimages with different radiopharmaceuticals areshowed in Figs. 1.1 and 1.2.

–  Differentiation ofbenign frommalignant lesions–  Searching for anunknown primarytumour–  Staging patientswith knownmalignancies–  Monitoring theeffect of therapy–  Detecting tumourrecurrence–  Guiding biopsy–  Guiding radiationtherapy planning–  Detecting prostatecancer recurrence–  Staging of high-riskprostate cancer–  Monitoring theeffect of therapy inadvanced orcastration-resistantprostate cancerF- FDG18F-Choline18Clinical indication inoncologyMetabolictracersIntense uptake:grey matter,myocardium,urinary tracts,bladderMild uptakeLiver, spleen,bowel and bonemarrowIntense uptakeSalivary glands,liver, pancreas,spleen, kidney,urinary tracts,bladderMild uptakeLacrimalglands, boweland bonemarrowDepends on theexpression ofGLUT1 transportand hexokinasephosphorylation.3.7–5.2 MBq/kgDependent onthe system, time for a body PET/CTper bed position scanand thepatient’s weight3–4 MBq/kg60 minDual phaseprocedure: astaticacquisition ofthe pelvisimmediatelyafter injectionfollowed by awhole bodyscan 60 minafter injectionFasting (4 h)No physicalactivity (1 day)Empty bladderDepends on theexpression ofcholine transportersand choline kinaseactivity.Fasting (4 h)No physicalactivity (1 day)Empty bladderNot applicableRecommended Paediatricrecommendedactivity inactivityadultsTime frominjection toacquisitionUptake mechanism PhysiologicalPatientbiodistribution preparationTable 1.4 Metabolic and pure isotope PET tracers(continued)3.0E 2Effectivedose foradults(mSv/MBq)1.9E 021Introduction to Different PET Radiopharmaceuticals and Hybrid Modalities (PET/CT and PET/MRI)7

F-DOPA18–  Detection ofinsulinomas,paragangliomas andpheochromocytoma–  Detecting medullarythyroid cancerrecurrence–  Staging ofmedullary thyroidcancer–  Staging andrestaging ofneuroblastoma–  Detecting prostatecancer recurrence–  Staging of high-riskprostate cancer–  Monitoring theeffect of therapy inadvanced orcastration-resistantprostate cancer18F-Fluociclovine Detecting earlyprostate cancerrecurrence11C-CholineTable 1.4 (continued)Depends on theexpression of largeneutral amino acidtransporter (LAT)Depend on theexpression of l-typeamino r 2 (LAT/ASCT2)Depends on theexpression ofcholine transportersand choline kinaseactivityIntense uptakeSalivary glands,liver, pancreas,spleen, kidneyMild uptakeLacrimalglands, boweland bonemarrowIntense uptakeLiver andpancreasMild uptakeLacrimalglands, salivarygland, boweland bonemarrowIntense uptakebasal ganglia,pancreas,gallbladder,kidney andbladderMild uptakeSalivary gland,liver, bowel andbone marrow370 MBq3–5 min10–60 minFasting (4 h)No physicalactivity (1 day)Empty bladderFasting (4 h)Empty bladder2–4 MBq/kg370 MBq0–15 minFasting (6 h)Empty bladder4 MBq/kgNot applicableNot applicable2.5E 022.2E 24.9E 38L. Giovanella et al.

I- NaI64CuCl212418F- NaFChemisorption offluoride ions ontothe surface ofhydroxyapatitedepending on boneblood flow andosteoblastic activity–  Detect differentiated Depends on sodium/iodide symporterthyroid cancer(NIS) expression(DTC) recurrence–  Select patients forfurther radioiodinetreatment–  Dosimetric studiesfor radioiodinetreatmentDepends on humanDetecting earlycopper transport 1prostate cancer(HCTR1)recurrenceDetection of bonemetastases250 MBq24–80 MBq24,72, 96 hInjection ofrecombinanthuman TSH or2–4 weeks ofthyroidhormonewithdrawal1h1.5–3.7 MBq/kgNot applicable22–60 MBq2.2 MBq/kgRecommended Paediatricrecommendedactivity inactivityadults30–45 minTime frominjection toacquisitionEmpty bladderHigh uptake in Fasting (4 h)the liver andless intenseuptake insalivary glands,biliary tract,pancreas, spleenand kidneyIntense uptakeSalivary glands,oral cavity,gastrointestinaltract, bladderUniform tracerdistributionthroughout theskeletonPure isotopes as Clinical indications in Uptake mechanism PhysiologicalPatientPET tracersoncologybiodistribution preparation2.9E 29.5E 2 (for0% thyroiduptake)Effectivedose foradults(mSv/MBq)2.4E 21Introduction to Different PET Radiopharmaceuticals and Hybrid Modalities (PET/CT and PET/MRI)9

Receptor tracersIndications (oncology)68Ga-DOTA–  Localization ofconjugated peptidesneuroendocrine tumoursand detection ofmetastatic disease(staging)–  Monitoring the effect oftherapy in these patients–  Select patients withmetastatic disease forsomatostatin receptorradionuclide therapy64Cu-DOTA–  Localization ofconjugated peptidesneuroendocrine tumoursand detection ofmetastatic disease(staging)–  Monitoring the effect oftherapy in these patients–  Select patients withmetastatic disease forsomatostatin receptorradionuclide therapy68Ga-PSMA–  Detecting prostate cancerrecurrence–  Staging of high-riskprostate cancer–  Monitoring of systemictreatment in metastaticprostate cancerTable 1.5 Receptor PET tracersPhysiologicalbiodistributionIntense uptakeLiver, spleen,kidney, bladderModerate uptakePituitary gland,salivary glandsIntense uptakeLiver, spleen,kidney, bladderModerate uptakePituitary gland,salivary glands,bowelIntense uptakeSalivary glands,kidney, bladder,liver, spleen,bowelUptakemechanismDepends on theexpression ofsomatostatinreceptors (SSTR)Depends on theexpression ofsomatostatinreceptors (SSTR)Depends onincreased PSMAexpression200 MBq1.8–2.2/kg60 min60 minNo need for fastingbefore injectionNo consensus ondiscontinuation ofcold octreotidetherapyPatients do not needto fast and areallowed to take alltheir medicationsPatient preparationNo need for fastingbefore injectionNo consensus ondiscontinuation ofcold octreotidetherapyRecommendedactivity inadults100–200 MBqTime frominjectiontoacquisition60 minNot applicableNot tomaproposed2.6 MBq/kg2.0E 23.2E 2Effectivedose foradults(mSv/MBq)2.2E 210L. Giovanella et al.

F-PSMA18F- FES64Cu-PSMA18–  Detecting disease relapsein breast cancer patientswith high levels ofoestrogen receptors–  Predicting response toendocrine treatment inmetastatic breast cancerpatients–  Detecting prostate cancerrecurrence–  Staging of high-riskprostate cancer–  Monitoring of systemictreatment in metastaticprostate cancer–  Detecting prostate cancerrecurrenceDepends on theexpression ofoestrogenreceptorsDepends onincreased PSMAexpressionDepends onincreased PSMAexpressionIntense uptakeSalivary glands,kidney, bladder,liver, spleen,bowelIntense uptakeLiver, bile duct,intestinal tractand bladderIntense uptakeSalivary glands,kidney, bladder,liver, spleen,bowel350 MBq315 MBq200 MBq90 min60 minPatients do not needto fast and areallowed to take alltheir medications.Patients do not needto fast and areallowed to take alltheir medications–  Discontinuation of 60 minoestrogensreceptorantagonist fo5 days. Aromataseinhibitors areallowed–  Premenopausalpatients mighthave impaireduptake of 18F-FESbecause ofcompetitivebinding byendogenousoestrogensNot applicableNot applicableNot applicable2.2E 22.5E 21.3E 21Introduction to Different PET Radiopharmaceuticals and Hybrid Modalities (PET/CT and PET/MRI)11

18F-DOPABrain tracers18F- FDGEffectivedose peradministrationactivity forPaediatricWaiting time fromradiopharmaceutical Recommended recommended adults (mSv/MBq)activity in adults activityClinical indicationsUptake mechanism Biodistribution Patient preparation administration30–60 min150–250 MBq 0.1 mCi/kgIntense uptake –  Fasting (4 h)Depends on theNeurology1.9E 02Grey matter–  Empty bladder–  Early and differential diagnosis expression of–  Centrally actingGLUT1 transportof dementiapharmaceuticalsand hexokinase–  Epilepsyshould bephosphorylation–  Differentiation betweendiscontinued onParkinson’s disease andthe day of theatypical parkinsonianPET scansyndromesaccording to theNeurooncologyclinical status of–  Differential diagnosis ofthe patientcerebral lesions, detection ofviable tumour tissue and forgrading185 MBq74–111 MBq 2.5E 02–  Depends on the Intense uptake –  Fasting (4 h)NeurologyNeurologyactivity ofBasal ganglia –  Empty bladder 70–90 min–  To differentiate essential tremorenzyme aromatic Low-moderate –  Premedication Neurooncologyfrom parkinsonian syndromesamino acidwith carbidopa 10–30 minuptake–  Differentiation between Lewydecarboxylase(2 mg/kg) 1 hGrey matterbody disease and otherconvertingbefore thedementias6-18F-L-dopa ininjection–  To differentiate degenerativefrom non-degenerativefluorodopamineparkinsonism–  Depends on the–  To detect early presynapticexpression ofparkinsonian syndromeslarge neutralNeurooncology (glioma)amino acid–  Differentiation of grade III andtransporter (LAT)IV gliomas from nonneoplasticlesions or grade I and IIgliomas–  Prognostication of gliomas–  Definition of the optimal biopsysite–  Diagnosis of tumour recurrence–  Disease and therapy monitoringTable 1.6 Brain PET tracers12L. Giovanella et al.

C- MET11Neurooncology (glioma)–  Differentiation of grade III andIV tumours from nonneoplasticlesions or grade I and IIgliomas–  Prognostication of gliomas–  Definition of the optimal biopsysite–  Diagnosis of tumour recurrence–  Disease and therapy monitoringNeurooncology (glioma)See 18F-FETDepends on theexpression of largeneutral amino acidtransporter (LAT)High affinityamyloid-betaneuritic plaquesDepends on theexpression of largeneutral amino acidtransporter (LAT)18F-Flutemetamol Patients with a diagnosis ofpossible Alzheimer disease ormild cognitive impairment whenthe diagnosis is uncertain aftermorphological the and functionalneuroimaging18High affinityF-Florbetaben Patients with a diagnosis ofamyloid-betapossible Alzheimer disease ormild cognitive impairment when neuritic plaquesthe diagnosis is uncertain aftermorphological the and functionalneuroimagingF- FET1820 min10 min90 min90 minFasting (4 h)–  Empty bladderFasting (4 h)–  Empty bladder–  Empty bladder–  Empty bladderLow uptakeWhite matterLow uptakeWhite matterLow uptakeGrey matterLow uptakeGrey matter300 MBq185 MBq370 MBq185 MBq5.0E 031.6E 2Not applicable 1.9E 2Not applicable 3.5E 211 MBq/kg100 MBq1Introduction to Different PET Radiopharmaceuticals and Hybrid Modalities (PET/CT and PET/MRI)13

L. Giovanella et al.14abcdFig. 1.1 Biodistribution of PET tracers: 18F-FDG (a), 18F-FCH (b), 18F-DOPA (c), 18F-Fluociclovine (d)abcdeFig. 1.2 Biodistribution of PET tracers: 18F-NaF (a), 64CuCl2 (b) 68Ga-DOTATOC (c), 68Ga-PSMA (d), 18F-FES (e)References1. Saha GB. Basics of PET imaging: physics, chemistry,and regulations. New York: Springer; 2010.2. Zanzonico P. Positron emission tomography: areview of basic principles, scanner design and performance, and current systems. Semin Nucl Med.2004;34(2):87–111.3. Slomka PJ, Pan T, Germano G. Recent advances andfuture progress in PET instrumentation. Semin NuclMed. 2016;46(1):5–19.4. Alessio A, Kinahan P. PET imaging io/papers/alessioPETRecon.pdf.5. Waterstram-Rich KE, Christian PE. Nuclear medicineand PET/CT: technology and techniques. St. Louis:Elsevier Mosby; 2012.6. Li S, Tavares JMRS. Shape analysis in

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