C-11-Acetate can act as a probe of tissue metabolism through entry into catabolic or anabolic metabolic pathways as mediated by acetyl-coenzyme A. The uptake of C-11-acetate in prostate cancer was investigated to determine whether this tracer has potential in tumor identification. Methods: Twenty-two patients with prostate cancer underwent PET after intravenous administration of 740 MBq C-11-acetate. Eighteen of the 22 patients were also investigated with F-18-FDG PET. Standardized uptake values (SUVs) for each tumor were investigated for tracer activity at 10-20 min after C-11-acetate and 40-60 min after F-18-FDG administration. Results: Adenocarcinoma of the prostate showed variable uptake of C-11-acetate, with SUVs ranging from 3.27 to 9.87. In contrast, SUVs for F-18-FDG ranged from 1.97 to 6.34. By visual inspection, C-11-acetate accumulation in primary prostate tumors was positive in all patients, whereas 18F-FDG accumulation was positive in only 15 of 18 patients. C-11-Acetate PET in a patient with lymph node metastasis showed high intrapelvic accumulation corresponding to metastatic sites. Similarly, 2 patients with bone metastases were C-11-acetate avid. Conclusion: C-11-Acetate shows marked uptake in prostate cancer and is more sensitive in detection of prostate cancer than is F-18-FDG PET. C-11-Acetate represents a new tracer for detection of prostate cancer with PET, measuring radiopharmaceutical uptake pathways that are different from those measured by F-18-FDG.