Establishment of a Zr(IV) blood plasma model

Abstract

This study was carried out in an effort to verify ⁸⁹Zr as a new safe and effective nuclide for immuno-PET imaging. In recent years, immuno-PET imaging has been of increasing importance in cancer diagnostics due to its rare abilities. This diagnostic tool has the ability to selectively target tumours thus allowing patients with cancers associated with poor prognosis to be identified in early stages of the disease. One of the cancers associated with poor prognosis is the epithelial ovarian cancer. At present, epithelial ovarian cancer is the fifth leading form of cancer resulting in deaths of women in the United States of America and possibly the rest of the world. The high mortality rate associated with epithelial ovarian cancer is the basis of this research because it shows that there is a need to develop effective tracers. The stability and the in vivo robustness of the ⁸⁹Zr-DFO chelator system as part of potential immuno-PET radiopharmaceuticals was investigated by means of potentiometry and computer simulation of blood plasma. Glass electrode potentiometry was used to measure formation constants of the complexation of Zr⁴⁺ with DFO and the competing blood plasma ligands. This made the construction of the blood plasma model possible because the formation constants that were attained were used in ECCLES blood plasma model to evaluate the competitive stability of the ⁸⁹Zr-DFO chelator system against biological metal ions and ligands. The results of the ECCLES blood plasma model showed that 99.7 % of Zr⁴⁺ ions will not dissociate from the ⁸⁹Zr-DFO complex when administered at a concentration of 8.5 x 10⁻⁵ mol.dm⁻³.This was a positive result showing that almost all of the metal ions will reach the targeted area, however, the ligand on the other hand proved to be less stable resulting in a 10 % stability. The model showed that 88.6 % of the ligand will dissociate to form a complex with Fe³⁺ thus leading to a significant mobilization of the metal ion in the blood plasma.