PET in Prostate Cancer Tom R. Miller, M.D., Ph.D. Mallinckrodt Institute of Radiology Washington University School of Medicine St. Louis, Missouri, USA
Prostate Imaging Bone Scintigraphy primarily for patients with high PSA CT and MRI relatively ineffective small nodes considered normal false negatives
Prostate Imaging Radiopharmaceuticals Prostascint (In-111 capromab pendetide) F-18 FDG C-11 Acetate C-11 Choline F-18 Fluorocholine
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
Prostate Imaging Carbon-11 Acetate C-11 acetate developed in the 1970s to measure myocardial oxidative metabolism
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
77 y/o man with PSA recurrence following prostatectomy pan n n u b C-11 Acetate F-18 FDG
Biopsy proven prostate recurrence following RT n p C-11 Acetate F-18 FDG
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
80 y/o man pre-rt?? CT C-11 acetate F-18 FDG
80 y/o man pre-rt C-11 acetate F-18 FDG CT
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 0.5-47.5) Oyama et al, J Nucl Med 44: 549-555, 2003
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
Other Imaging Modalities CT: 3/22 (14%) lymph nodes Bone scan: 2/22 (9%) metastases
High probability findings as a function of PSA
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
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
PET in Newly Diagnosed Prostate Cancer Initial staging All patients High-risk patients Guide treatment Estimate prognosis
PET in Initial Staging PET likely better than CT or MRI (except in determination of capsular invasion or seminal vesicle involvement) Identification of lymphadenopathy
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» 14-18 % (Gleason 7-10) Partin et al, Urology 58: 843-848, 2001
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
PET in Patients Treated by Radiation Therapy Identify regional lymph nodes to aid in selection of ports
PET in Estimating Prognosis A positive PET may imply a poorer prognosis
C-11 Acetate C-11 Choline Kotzerke et al, Nuclearmedizin 2003
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
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.