Preparation and metabolism of a cisplatin/serum protein complex.

195mPt-cis-Dichlorodiammine platinum(II) (195mPt-cisplatin) binds in vitro essentially irreversibly to bovine serum albumin (BSA) and rat plasma proteins at a 195mPt-cisplatin/protein molar ratio of 1:1 or less. The binding to rat serum proteins shows no apparent specificity, with albumin retaining the greatest fraction of the label (40-55%). The binding is neither instantaneous nor linear with time. Upon intravenous administration to rats of a rat serum protein bound 195mPt-cisplatin, the label remains bound to the proteins while in the blood. The label is cleared from the blood faster than a relatively native 131I-labeled human serum albumin (HSA) and accumulates primarily in the liver. The blood disappearance and organ distribution of the rat serum protein bound 195mPt-cisplatin is consistent with a modified protein. Approx. 11% of the injected dose was excreted via the urine in 24 h in a form which has a different chromatographic mobility than free 195mPt-cisplatin. Since little intact protein is lost in the urine, the excreted label probably represents the product(s) of metabolism of the rat serum bound 195mPt-cisplatin. Due to the apparent irreversibility (both in vivo and in vitro) of the protein/195mPt-cisplatin complex, it is unlikely that the protein bound fraction of the administered 'free' drug will serve as a therapeutically useful 'drug resevoir'.