PETCT in Oncology PET Tracers other than FDG

PET/CT in Oncology: PET Tracers other than FDG M. Wissmeyer Department of Nuclear Medicine, University of Berne (Inselspital)

PET – Isotopes and Half Lives Ø 15 O 2 Minutes Ø 13 N 10 Minutes Ø 11 C 20 Minutes Ø 18 F 110 Minutes Ø 68 Ga 68 Minutes

PET - Radiopharmaceuticals ØAminoacids: 11 C-Methionine ØProteinsynthesis: 18 F-Ethyltyrosine ØProliferation: (FET) 11 C-Thymidine, 18 F- Fluorthymidine (FLT) ØHypoxia: 18 F-Fluoromisonidazole ØMineralisation (Skeleton): 18 F-Fluoride ØCell Membranes: 11 C- ØFatty Acids: 11 C-Acetate ØAPUD Cell System: 18 F-DOPA ØReceptor ligands: 68 Ga-Petpides (e. g. or 18 F-Choline DOTA-TOC)

Aminoacids: 11 C-Methionine ØDrawback: Short Halflife => Cyclotron onsite indispensable ØTransporter mediated Uptake ØNo significant Metabolism in Proteinsynthesis ØWell established in Brain Tumours (positive Marker!)

Aminoacids: 11 C-Methionine ØSensitivity up to 91% for Gliomas (n=23) Jacobs AH et al. , JNM 12/2005

Aminoacids: 11 C-Methionine ØMethionine superior to FDG in Follow up of treated Gliomas ØSensitivity 89%, Specificity 29%, Accuracy 72% (11%, 100%, 36%, respectively) Methionine FDG Pötzi et al. , J Neurooncol 2007

Aminoacids: 11 C-Methionine ØPromising in Monitoring Chemotherapy Galldiks et al. , EJNMMI 05/2006

Aminoacids: 11 C-Methionine Grosu et al. , IJROBP 02/2006

Aminoacids: 18 F-FET ØHalflife 110 Min. => Cyclotron onsite not required ØTransporter mediated Uptake ØNo significant Metabolism in Proteinsynthesis ØWell established in Brain Tumours (positive Marker!)

Aminoacids: 18 F-FET ØGliomas: FET + MRI => Sensitivity 93%, Specificity 94% (n=26) ØVariable Uptake in Low Grade Gliomas => No SUV-Cutoff Ø 1/3 of Astrozytoma Grade II => No FET Uptake (similar to 11 CMethionine) ØPromising Tool in Detection of Recurrency Langen KJ et al. , NMB 2006

Aminoacids: 18 F-FET ØGliomas: FET => Sensitivity 92%, Specificity 81%, Accuracy 92% (n=26) ØSignificantly better than MRI alone in Assessment of Gliomas Pauleit D et al. , Brain 2005

Aminoacids: 18 F-FET ØHigh Value in Prediction of Prognosis of cerebral Gliomas Floeth FW et al. , JNM 04/2007

Aminoacids: 18 F-FET ØPoor Results in peripheral Tumours ØFDG (A) and FET (B) PET in Lymphoma (left) and Head and Neck Cancer (right) Pauleit D et al. , JNM 2005

Proliferation: 18 F-FLT ØHalflife 110 Min. => Cyclotron onsite not required ØNucleosid Analogue (Pyrimidin) ØUptake by passive Diffusion / facilitated Transport ØCellular Trapping after Phosphorylation by Thymidinkinase

Proliferation: 18 F-FLT ØPromising Results cerebral Gliomas: Primary Diagnosis Saga T et al. , Clin Nucl Med 2006

Proliferation: 18 F-FLT ØPromising Results cerebral Gliomas: Suspected Recurrence Saga T et al. , Clin Nucl Med 2006

Proliferation: 18 F-FLT ØEarly Assessment of Therapy Reponse: Malignant Lymphoma ØMouse Model ØLymphoma Treated with ØChemotherapy (n=10) ØImmunotherapy (CD 20 m. AB; n=10) ØRadioimmunotherapy (90 Y-CD 20 (Zevalin); n=10) ØFLT detects Tumour Response earlier than morphologic Imaging Buck AK et al. , EJNMMI 2007, in press

Proliferation: 18 F-FLT ØSignificant Impact on Target Volumes in RT in rectal Cancer (Patel DA et al. , TCRT 02/2007) Ø Drawbacks in Lymph Node Imaging in Primary Head and Neck Cancer (Troost EGC et al. , JNM 2007)

Hypoxia: 18 F-Misonidazole ØHalflife 110 Min. => Cyclotron onsite not required ØPresence of hypoxic Tissue Predicts Outcome of RT ØHypoxia => Increased Tumour Aggressivity => Decreased Response to Therapy => Poor Outcome ØMost published Results in Head and Neck Cancer ØImpact on Target Volume Definition in RT

Hypoxia: 18 F-Misonidazole ØOutcome in Head and Neck Cancer: FDG vs. F-MISO Rajendran JG et al. , Clin Cancer Res 09/2006

Hypoxia: 18 F-Misonidazole ØF-MISO Uptake during RT in Head and Neck Cancer Eschmann SM et al. , Radiotherapy and Oncology 2007; in press

Hypoxia: 18 F-Misonidazole ØDose Painting Using F-MISO Information Thorwarth D et al. , IJROBP 2007

Mineralisation: 18 F-Fluoride ØHalflife 110 Min. => Cyclotron onsite not required ØSignificantly higher Bone Uptake than 99 m. Tc-Phosphonates ØBlood Clearance faster than 99 m. Tc-Phosphonates => Higher Contrast ØPlanar Scintigraphy more available than PET-Scanners

Mineralisation: 18 F-Fluoride ØBone Scan vs. Fluoride PET Schirrmeister H et al. , JCO 1999

Mineralisation: 18 F-Fluoride ØNormal Bone Scan vs. Pathologic Fluoride PET Schirrmeister H et al. , JCO 1999

Mineralisation: 18 F-Fluoride ØPathologic Bone Scan vs. Extensive Metastases in Fluoride PET Schirrmeister H et al. , JCO 1999

Cell Membranes: 11 C- / 18 F-Choline Ø 11 C-Choline: Halflife 20 Min. => Cyclotron onsite required Ø 18 F-Choline: Halflife 110 Min. => Cyclotron onsite not required ØFirst Results for a Variety of Tumours ØMost Studies in Prostate Cancer ØOngoing multicentric Trial on Choline PET/CT in initial Staging of Prostate Cancer

Cell Membranes: 11 C- / 18 F-Choline Ø 11 C-Choline vs. FDG in various Tumours Tian M et al. , EJNMMI 2004

Cell Membranes: 11 C- / 18 F-Choline Ø 11 C-Choline vs. FDG in various Tumours Tian M et al. , EJNMMI 2004

Cell Membranes: 11 C- / 18 F-Choline Ø 18 F-Choline in Prostate Cancer: Diagnosis of Relapse Cimitan M et al. , EJNMMI 2006

Cell Membranes: 11 C- / 18 F-Choline Ø 18 F-Choline in Prostate Cancer: Diagnosis of Relapse Cimitan M et al. , EJNMMI 2006

Cell Membranes: 11 C- / 18 F-Choline Ø 18 F-Choline in Prostate Cancer: Own Experience G. G. , 62 y; mediastinal LN Metastasis

Fatty Acids: 11 C-Acetate ØHalflife 20 Min. => Cyclotron onsite required ØIncreased Uptake in slowly growing Tumours ØPotential Advantage in FDG negative Tumours ØMost Evidence in Prostate Cancer and Myocardial Imaging ØFirst Studies in Adenocarcinoma of the Lung

Fatty Acids: 11 C-Acetate ØAcetate PET/CT in recurrent Prostate Cancer Albrecht S et al. , EJNMMI 2007

APUD Cell System: 18 F-DOPA ØHalflife 110 Min. => Cyclotron onsite not required ØKatecholamine Metabolite Analogue ØActive Uptake in APUD Cells ØDecarboxylation => No further Metabolism => Accumulation ØWell established in Neuro-Imaging and 111 In-Octreotide negative neuroendocrine Carcinomas

APUD Cell System: 18 F-DOPA ØF-DOPA vs. 111 In-Octreotide in GEP Tumours Ambrosini V et al. , Nucl Med Commun 2007

APUD Cell System: 18 F-DOPA ØF-DOPA vs. FDG PET/CT in GEP Tumours Nanni C et al. , EJNMMI 2006

APUD Cell System: 18 F-DOPA ØF-DOPA vs. FDG PET in Medullary Thyroid Carcinoma Beuthien-Baumann B et al. , EJNMMI 2007

APUD Cell System: 18 F-DOPA Ø 111 In-Octreotide vs. 18 F-DOPA in typical Carcinoid B. L. , f, 70 y; Liver and mesenteric LN Metastases

Receptor Ligands: 68 Ga-Peptides ØHalflife 68 Min. ØGenerator Product ØSynthesis of Radiopharmaceutical onsite ØPeptides: Somatostatin Analogues ØLinked to Somatostatin Receptors of Neuroendocrine Tumours ØHigh Specificity für Somatostatine Receptor Subtypes II and V ØFirst Results: Sensitivity and Accuracy much higher than for 111 In-Octreotide

Receptor Ligands: 68 Ga-Peptides ØResults of a valuable Clinical Trial (n=84) Gabriel M et al. , JNM 2007

Receptor Ligands: 68 Ga-Peptides ØOwn Experience: 111 In-Octreotide vs. DOTATOC PET/CT W. P. , 61 y, m, Pancreatic NET, multiple Metastases; Courtesy Dr. M. Hofmann

Receptor Ligands: 68 Ga-Peptides ØOwn Experience W. P. , 61 y, m, Pancreatic NET, multiple Metastases; Courtesy Dr. M. Hofmann

Conclusions ØVariety of promising PET Tracers besides FDG ØData limited mostly due to small Size of Cohorts Ø 11 C labelled Tracers restricted to Centers with Cyclotron onsite ØGrowing Field of 18 F labelled Tracers Ø 68 Ga as new promising Generator Product in Neuroendocrine Tumours