Noninvasive measurements for studying the tumoral pharmacokinetics of platinum anticancer drugs in solid tumors

An effective methodology to determine the amount of cisplatin or carboplati n at the solid tumor site in a noninvasive manner may enable clinicians to design drug regimens based on an individual's in situ pharmacokinetics. Suc h noninvasive methods may allow optimization of an individual's drug exposu re at the target site, as well as provide a screening measure to determine individual efficacy based on exposure to these platinated drugs. Pt-195m ap pears to be the radionuclide of platinum most suitable for radiolabeling ci splatin or carboplatin, and an analysis is presented of the methods availab le for preparing such radiolabeled drugs. The use of this methodology is il lustrated in detail in studies in animals, as well as some preliminary stud ies in humans. The animals used were Sprague Dawley rats bearing the Walker 256 carcinoma, and drug biodistribution was studied following administrati on of cisplatin or carboplatin radiolabeled with Pt-195m. This radionuclide permitted noninvasive imaging of the drug and its metabolites at the tumor site and at selected organs. The results obtained show an ability to estim ate the amount of platinated drug species in the tumor environment using a noninvasive methodology. Various compartmental models were tested, some of which could be validated experimentally. This noninvasive method is able to provide individual estimates of the active component of the drug at the ta rget site, and is therefore a method that can be implemented in human studi es. (C) 2000 Elsevier Science B.V. All rights reserved.