Microscale synthesis and biodistribution of Pt-195m-labeled cis-dichlorodiammineplatinum(II), cis-DDP

Cis-DDP is a unique metal based antitumor drug which exhibits potent activity toward cancers of genitourinary origin. The major dose-limiting side-effect of cis-DDP is nephrotoxicity, which limits broader clinical use. We have initiated studies using Pt-195m-labeled cis-DDP to elucidate the critical pharmacological parameters affecting nephrotoxicity. The general details of the optimized microscale synthesis (50 μmole scale), the effects of varying the dose and concentration of cis-DDP, and the use of a diuretic on the biodistribution of Pt-195m-labeled cis-DDP are as follows: (1) yields of cis-DDP average 75%, (2) the product meets the well-defined purity criteria established for cis-DDP, (3) the % dose retained/gm tissue is independent of both dose and concentration (at a fixed dose) of cis-DDP, and (4) injection of the diuretic furosemide at 2 and 4 mg/kg leads to enhanced retention of Pt-195m in most organs at 24 hours. The potential clinical implications of these results are discussed