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

2. PET – Isotopes and Half Lives  15 O2 Minutes  13 N10 Minutes  11 C20 Minutes  18 F110 Minutes  68 Ga 68 Minutes

3. PET - Radiopharmaceuticals  Aminoacids: 11 C-Methionine  Proteinsynthesis: 18 F-Ethyltyrosine (FET)  Proliferation: 11 C-Thymidine, 18 F-Fluorthymidine (FLT)  Hypoxia: 18 F-Fluoromisonidazole  Mineralisation (Skeleton): 18 F-Fluoride  Cell Membranes: 11 C- or 18 F-Choline  Fatty Acids: 11 C-Acetate  APUD Cell System: 18 F-DOPA  Receptor ligands: 68 Ga-Petpides (e.g. DOTA-TOC)

4. Aminoacids: 11 C-Methionine  Drawback: Short Halflife => Cyclotron onsite indispensable  Transporter mediated Uptake  No significant Metabolism in Proteinsynthesis  Well established in Brain Tumours (positive Marker!)

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

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

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

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

9. Aminoacids: 18 F-FET  Halflife 110 Min. => Cyclotron onsite not required  Transporter mediated Uptake  No significant Metabolism in Proteinsynthesis  Well established in Brain Tumours (positive Marker!)

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

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

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

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

14. Proliferation: 18 F-FLT  Halflife 110 Min. => Cyclotron onsite not required  Nucleosid Analogue (Pyrimidin)  Uptake by passive Diffusion / facilitated Transport  Cellular Trapping after Phosphorylation by Thymidinkinase

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

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

17. Proliferation: 18 F-FLT  Early Assessment of Therapy Reponse: Malignant Lymphoma  Mouse Model  Lymphoma Treated with  Chemotherapy (n=10)  Immunotherapy (CD20 mAB; n=10)  Radioimmunotherapy ( 90 Y-CD20 (Zevalin); n=10)  FLT detects Tumour Response earlier than morphologic Imaging Buck AK et al., EJNMMI 2007, in press

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

19. Hypoxia: 18 F-Misonidazole  Halflife 110 Min. => Cyclotron onsite not required  Presence of hypoxic Tissue Predicts Outcome of RT  Hypoxia => Increased Tumour Aggressivity => Decreased Response to Therapy => Poor Outcome  Most published Results in Head and Neck Cancer  Impact on Target Volume Definition in RT

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

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

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

23. Mineralisation: 18 F-Fluoride  Halflife 110 Min. => Cyclotron onsite not required  Significantly higher Bone Uptake than 99m Tc-Phosphonates  Blood Clearance faster than 99mTc-Phosphonates => Higher Contrast  Planar Scintigraphy more available than PET-Scanners

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

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

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

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

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

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

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

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

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

33. Fatty Acids: 11 C-Acetate  Halflife 20 Min. => Cyclotron onsite required  Increased Uptake in slowly growing Tumours  Potential Advantage in FDG negative Tumours  Most Evidence in Prostate Cancer and Myocardial Imaging  First Studies in Adenocarcinoma of the Lung

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

35. APUD Cell System: 18 F-DOPA  Halflife 110 Min. => Cyclotron onsite not required  Katecholamine Metabolite Analogue  Active Uptake in APUD Cells  Decarboxylation => No further Metabolism => Accumulation  Well established in Neuro-Imaging and 111 In-Octreotide negative neuroendocrine Carcinomas

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

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

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

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

40. Receptor Ligands: 68 Ga-Peptides  Halflife 68 Min.  Generator Product  Synthesis of Radiopharmaceutical onsite  Peptides: Somatostatin Analogues  Linked to Somatostatin Receptors of Neuroendocrine Tumours  High Specificity für Somatostatine Receptor Subtypes II and V  First Results: Sensitivity and Accuracy much higher than for 111 In-Octreotide

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

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

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

44. Conclusions  Variety of promising PET Tracers besides FDG  Data limited mostly due to small Size of Cohorts  11 C labelled Tracers restricted to Centers with Cyclotron onsite  Growing Field of 18 F labelled Tracers  68 Ga as new promising Generator Product in Neuroendocrine Tumours