Blood plasma model predictions for the proposed bone-seeking radiopharmaceutical [117mSn]Sn(IV)-N,N′,N′-trimethylenephosphonate-poly(ethyleneimine)

In an attempt to elucidate the in vivo stability of the prospective radiopharmaceutical [Sn-117m]Sn(IV)-PEI-MP, where PEI-MP stands for N, N',N'-trimethylenephosphonate-polyethyleneimine, glass electrode potentiometry was used to determine the stability constants of the Sn4+ ion as complexed with a variety of physiological amino acids. In addition, linear free energy relationship (LFER) correlation plots were used to extrapolate the constants of the major blood plasma ligands, based on data from Cu2+, Pb2+, and Zn2+. In so doing, a thermodynamic model of blood plasma was established for Sn4+ from which the complexation tendencies of Sn4+ were predicted in the event of the intravenous administration of such a drug. It was found that the Sn(IV)-PEI-MP could succumb to competition by the glutamine amino acid, which forms more stable complex(es), whilst the PEI-MP gets taken up largely by Ca2+. Also, this study shows the value of the in vitro experiments and modeling performed for radiopharmaceutical research and for attempts to reduce the number of animal experiments. (C) 2009 Elsevier Inc. All rights reserved.