[13N]cisplatin PET to assess pharmacokinetics of intra-arterial versus intravenous chemotherapy for malignant brain tumors.

The biodistribution, blood clearance, and in vivo transformation of cisplatin (cisdiaminedichloroplatinum, DDP) were studied in rats using 13N-labeled and unlabeled DDP. Following the i.v. injection of [13N]DDP, virtually no 13N activity was detected in brain tissue, and no measurable amount of the 13N label was displaced from [13N]DDP. Based on these results, [13N]DDP/positron emission tomographic (PET) scans were performed in two glioblastoma patients undergoing Phase II intra-arterial (i.a.) DDP chemotherapy: [13N]DDP was infused i.v. over 13-15 min, during which time serial PET scans were obtained. One hour later, [13N]DDP mixed with cold DDP (100 mg/m2 therapeutic dose) was infused at the same rate i.a., and a second sequence of PET scans was acquired. The pharmacologic advantage of i.a. administration was calculated as the ratio of integrated tumor/brain count ratios for the i.a. and i.v. studies. Our preliminary results demonstrate the feasibility of quantifying the pharmacologic advantage of i.a. DDP chemotherapy in individual brain tumor patients using [13N]DDP and PET.