Biodistribution and Pharamacokinetics of /Sup 195M/Pt-Labeled Cis-Dichlorotrans-Dihydroxo-Bis(Isopropylamine)Platinum(IV), CHIP, In Normal Female Fischer 344 Rat

摘要

The discovery and successful clinical application of the potent anti-tumor compound, cis-Dichlorodiammineplatinum(II), cis-DDP* has stimulated considerable interest in developing effective but less toxic second-generation platinum antitumor drugs. One such candidate drug is cis-Dichloro-trans-dihydroxo-bis-(isopropylamine)platinum(IV), cis-trans-(PtCl sub 2 (OH) sub 2 (i-PrNH sub 2 ) sub 2 ), (CHIP). 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 sarcoms. A microscale synthesis for /sup 195m/Pt-labelled CHIP and the tissue distribution and pharmacokinetic properties of this agent in normal female Fischer 344 rats are reported. A comparison with similar data for /sup 195m/Pt-cis-DDP is included. (ERA citation 08:047471)