Biodistribution and Pharmacokinetics of 195mPt-Labeled cis-Dichloro-trans-Dihydroxo-bis(Isopropylamine) Platinum (IV), CHIP, In the Normal Female Fischer 344 Rat

Abstract

The discovery and successful clinical application of the potent antitumor compound, cis-Dichlorodiammineplatinum(II), cis-DDP* has stimulated considerable interest in developing effective but less toxic secondgeneration platinum antitumor drugs. One such candidate drug is cis-Dichloro-trans-dihydroxo-bis-(isopropylamine)platinum(IV), cis-trans-[PtCl₂(0H)₂(i-PrNH₂)₂], (CHIP), the molecular structure of which is shown in Fig. 1. An important feature of this Pt(IV) agent is that in addition to exhibiting a generally milder clinical toxicity than cisplatin, the dose-limiting toxicity of CHIP is the more common myelosuppression rather than the less desirable nephrotoxicity. Also, CHIP has been reported recently to be more effective than cisplatin against both alkylating agent sensitive and resistant strains of the Yoshida sarcoma.¹ That CHIP is indeed a promising candidate drug is underscored by its selection by the National Cancer Institute as one of four new platinum analogs to enter clinical trials in the U.S.A.