Patients and Methods: [C-11]DACA(at 1/1,000 phase I starting dose) was administered to 24 patients with advanced cancer (pre-phase I) or during a phase I trial of DACA in five patients. Positron emission tomography (PET) was performed to assess pharmacokinetics and tumor blood flow. Plasma samples were analyzed for metabolite profile of [C-11]DACA.

Results:There was rapid systemic clearance of [C-11]DACA over 60 minutes (1.57 and 1.46 L . min(-1) . m(-2) in pre-phase I and phase I studies, respectively) with the production of several radiolabeled plasma metabolites. Tumor, brain, myocardium, vertebra, spleen, liver, lung, and kidneys showed appreciable uptake of C-11 radioactivity. The area under the time-versus-radio-activity curves (AUC) showed the highest variability in tumors. Of interest to potential toxicity, maximum radiotracer concentrations (Cmax) in brain and vertebra were low (0.67 and 0.54 m(2) . mL(-1), respectively) compared with other tissues. A moderate but significant correlation was observed for turner blood flow with AUC (r = 0.76; P =.02) and standardized uptake value (SUV) at 55 minutes (r = 0.79; P =.01). A decrease in myocardial AUC (P =.03) and splenic and myocardial SUV (P =.01 and .004, respectively) was seen in phase I studies. Significantly higher AUG, SUV, and Cmax were observed in turners in phase I studies.

Conclusion: The distribution of [C-11]DACA and its radiolabeled metabolites was observed in a variety of tumors and normal tissues. In the presence of unlabeled DACA, pharmacokinetics were altered in myocardium, spleen, and tumors. These data have implications for predicting activity and toxicity of DACA and support the use of PET early in drug development. J Clin Oncol 19:1421-1429. (C) 2001 by American Society of Clinical Oncology.