99mTc-NC100692--a tracer for imaging vitronectin receptors associated with angiogenesis: a preclinical investigation.

Introduction: Technetium 99m (99mTc)-NC100692 is being developed as a marker of vitronectin receptor expression. The purpose of this study was to confirm the binding affinity [dissociation constant (Kd)] of 99mTc-NC100692 for a range of integrin receptors including alphavbeta3 and alphavbeta5 as well as to establish the biodistribution and metabolic stability of 99mTc-NC100692 in Wistar rats.
Methods: The Kd of 99mTc-NC100692 for a range of human integrin receptors was established in an in vitro saturation binding assay. The biodistribution and metabolic stability of 99mTc-NC100692 in normal Wistar rats was investigated.
Results: The Kd of 99mTc-NC100692 to alphavbeta3 and alphavbeta5 was less than 1 nM. It was not possible to saturate the binding of 99mTc-NC10092 towards alphaIIbbeta3, alpha5beta1, alpha3beta1 or alpha1beta1, and as a result, accurate Kd values could not be determined. The biodistribution of 99mTc-NC100692 in male and female Wistar rats showed that radioactivity was rapidly excreted, predominantly into the urine, with very little background tissue retention apart from the liver and kidneys. Kidney and liver retention was reduced in the presence of excess NC100692 ligand. In vivo, there was little systemic metabolism of 99mTc-NC100692.
Conclusions: 99mTc-NC100692 has a high affinity for the vitronectin receptors that are associated with angiogenesis. 99mTc-NC100692 is metabolically stable in the systemic circulation of rats with a biodistribution that is favourable for imaging purposes. This evidence suggests that 99mTc-NC100692 might be a useful marker of vitronectin receptor expression in vivo.