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Physiological modeling of disposition of potential tumor‐imaging radiopharmaceuticals in tumor‐bearing mice

1992; Elsevier BV; Volume: 81; Issue: 5 Linguagem: Inglês

10.1002/jps.2600810503

1520-6017

David W. A. Bourne, Jeff Jacobs, Almah Bt. Awaluddin, D.J. Maddalena, J.G. Wilson, R.E. Boyd,

Chemical Reactions and Isotopes

Radiopharmaceuticals have great potential in the early detection of human tumors. Three potential 99mTc‐labeled platinum compounds based on cisplatin have been synthesized and tested in tumored mice. This report presents the analysis of the disposition data obtained after a single intravenous injection with an empirical, physiologically based pharmacokinetic model. The radioactivity of each radio‐pharmaceutical after administration was measured in blood, urine, and 15 tissues, including tumor. Parameters included in the model were tissue volumes (experimentally determined), tissue blood flows (determined from literature values), tissue:blood extraction ratios (determined by nonlinear least‐squares regression with MULTI‐FORTE), and clearance terms (also determined by nonlinear least‐squares regression). Data were weighted by the reciprocal of the square of the observed values. Good fits to the experimental data were obtained. As expected, the compound producing the best tumor:blood profile (3) also had the highest tumor extraction ratio (6.2 versus 2.0 and 1.3 for 1 and 2, respectively). Total body clearance values for the radioactivity associated with the three compounds 1–3 were calculated to be 0.09, 0.04, and 0.016 mL/min, respectively. Analysis of data with such an empirical, physiologically based model may assist future development of suitable tumor‐imaging agents.