Thermodynamic evaluation of the stability of the bone-seeking radiopharmaceutical [177Lu]Lu(III)-DOTP under simulated blood plasma conditions.

The stability and in vivo robustness of [(177)Lu]Lu-DOTP as a potential bone-targeting radiopharmaceutical was determined with the aid of thermodynamic blood plasma modeling simulations. Glass electrode potentiometry was employed to measure the stability constants of the complexes of Lu(3+) with DOTP. Similarly, the complexes of DOTP with a selection of the important physiological metal ions: Ca(2+), Mg(2+), and Cu(2+) were determined, representing the typical interactions that the ligand would encounter upon administration. This made possible the construction of a blood plasma model of DOTP, aiding in establishing the potential susceptibility of the radiopharmaceutical. The ligand binds predominantly to calcium in vivo, accounting for 59.6% of that initially introduced as a component of the Lu-DOTP complex. Furthermore, due to a preference of the DOTP to bind to Cu(2+) it causes mobilization of the ions in blood plasma, and would therefore indicate a deficiency if the ligand is administered at a concentration of 8.5 × 10(-5) mol dm(-3). The lutetium-ions are preferentially bound to DOTP, with as much as 98.1% of the Lu(3+) occupying the ligand under physiological conditions.