PET in Prostate Cancer

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1 PET in Prostate Cancer Tom R. Miller, M.D., Ph.D. Mallinckrodt Institute of Radiology Washington University School of Medicine St. Louis, Missouri, USA

2 Prostate Imaging Bone Scintigraphy primarily for patients with high PSA CT and MRI relatively ineffective small nodes considered normal false negatives

3 Prostate Imaging Radiopharmaceuticals Prostascint (In-111 capromab pendetide) F-18 FDG C-11 Acetate C-11 Choline F-18 Fluorocholine

4 Prostate Imaging Carbon-11 Acetate Initial studies in prostate cancer over the last 4 years Washington University Fukui University University of Michigan UCLA Ulm Hannover Dresden Hokkaido University

5 Prostate Imaging Carbon-11 Acetate C-11 acetate developed in the 1970s to measure myocardial oxidative metabolism

6 Metabolic Pathways of Acetate in Tumor Cells Myocardium Acetate rapidly taken up and subsequently metabolized to CO 2 via the TCA cycle (> 80%) Tumor Cells Tumor cells incorporate acetate preferentially into lipids rather than into amino acids or CO 2 Hypothesis: acetate preferentially incorporated into membrane lipids as a necessary condition for cell proliferation TCA Cycle CO 2 Acetate Acetyl-CoA Lipid Synthesis Metabolites Fatty Acids Courtesy BA Siegel Yoshimoto et al., Nucl Med Biol 2001

7 77 y/o man with PSA recurrence following prostatectomy pan n n u b C-11 Acetate F-18 FDG

8 Biopsy proven prostate recurrence following RT n p C-11 Acetate F-18 FDG

9 A B 73 y/o man with PSA recurrence 2 yr after RT n n n n n n F-18 FDG C-11 Acetate

10 80 y/o man pre-rt?? CT C-11 acetate F-18 FDG

11 80 y/o man pre-rt C-11 acetate F-18 FDG CT

12 C-11 Acetate in Recurrent Prostate Cancer 46 patients with recurrent disease All patients underwent imaging on the same day with both F-18 F FDG (15 mci) and C-11 C acetate (30 mci) Rising PSA after primary treatment by surgery (30) or radiation therapy (16) mean PSA 5.2 ng/ml (range ) Oyama et al, J Nucl Med 44: , 2003

13 Positive PET Studies AC PET FDG PET High prob 14/46 (30%) 4/46 (9%) Intermediate prob 13/46 (28%) 4/46 (9%) Overall Positive Results 27/46 (59%) 8/46 (17%) High probability: Biopsy, definite CT or bone scan correlate, characteristic appearance (intense, focal) Intermediate probability: Lesser intensity, possible bowel or bladder

14 Other Imaging Modalities CT: 3/22 (14%) lymph nodes Bone scan: 2/22 (9%) metastases

15 High probability findings as a function of PSA

16 C-11 Acetate in Recurrent Prostate Cancer C-11 acetate positive more frequently than F-18 F FDG (59% vs 17% or 30% vs 9%) C-11 acetate PET is not hampered by urinary excretion C-11 acetate is a promising tracer in this group of patients with recurrent disease

17 Other Potential Applications of PET in Prostate Cancer Direct initial diagnostic biopsy in patients with rising or elevated PSA Cancer vs benign prostatic hypertrophy: uptake seen in both Initial staging at time of diagnosis

18 PET in Newly Diagnosed Prostate Cancer Initial staging All patients High-risk patients Guide treatment Estimate prognosis

19 PET in Initial Staging PET likely better than CT or MRI (except in determination of capsular invasion or seminal vesicle involvement) Identification of lymphadenopathy

20 Initial Staging -Lymphadenopathy Non-palpable disease PSA 10, Gleason < 8» 0-4 % PSA > 10» 11 % (Gleason 8-10) Palpable disease PSA 10, Gleason < 8» 0-6 % PSA > 10» % (Gleason 7-10) Partin et al, Urology 58: , 2001

21 PET in Initial Staging May have a role in high-risk patients (PSA 10, Gleason 7) Most benefit if CT or MRI is negative or if used in place of those tests Unwarranted prostatectomy could be cancelled PET/CT

22 PET in Patients Treated by Radiation Therapy Identify regional lymph nodes to aid in selection of ports

23 PET in Estimating Prognosis A positive PET may imply a poorer prognosis

24 C-11 Acetate C-11 Choline Kotzerke et al, Nuclearmedizin 2003

25 Prostate PET - Future F-18 fluoroacetate In-house cyclotron not required Ongoing work in animal models at Washington University F-18 fluorodihydrotestosterone (FDHT) F-18 fluorothymidine (FLT) Choline, Fluorocholine

26 Colleagues Nobuyuki Oyama, M.D., Ph.D. Farrokh Dehdashti, M.D. Barry A. Siegel, M.D. Keith C. Fischer, M.D. Adam S. Kibel, M.D. Jeff M. Michalski, M.D. Gerald L. Andriole, M.D. Joel Picus, M.D. Michael J. Welch, Ph.D.