Specific uptake of 99mTc-NC100692, an αvβ3-targeted imaging probe, in subcutaneous and orthotopic tumors.

Abstract Introduction The α v β 3 integrin, which is expressed by angiogenic epithelium and some tumor cells, is an attractive target for the development of both imaging agents and therapeutics. While optimal implementation of α v β 3 -targeted therapeutics will require a priori identification of the presence of the target, the clinical evaluation of these compounds has typically not included parallel studies with α v β 3 -targeted diagnostics. This is at least partly due to the relatively limited availability of PET radiopharmaceuticals in comparison to those labeled with 99m Tc. In an effort to begin to address this limitation, we evaluated the tumor uptake of 99m Tc-NC100692, a cyclic RGD peptide that binds to α v β 3 with ~1-nM affinity, in an α v β 3 -positive tumor model as well as its in vivo specificity. Methods MicroSPECT imaging was used to assess the ability of cilengitide, a therapeutic with high affinity for α v β 3 , to block and displace 99m Tc-NC100692 in an orthotopic U87 glioma tumor. The specificity of 99m Tc-NC100692 was quantitatively evaluated in mice bearing subcutaneous U87MG tumors, by comparison of the biodistribution of 99m Tc-NC100692 with that of the non-specific structural analogue 99m Tc-AH-111744 and by blocking uptake of 99m Tc-NC100692 with excess unlabeled NC100692. Results MicroSPECT imaging studies demonstrated that uptake of 99m Tc-NC100692 in the intracranial tumor model was both blocked and displaced by the α v β 3 -targeted therapeutic cilengitide. Biodistribution studies provided quantitative confirmation of these imaging results. Tumor uptake of 99m Tc-NC100692 at 1h post-injection was 2.8±0.7% ID/g compared to 0.38±0.1% ID/g for 99m Tc-AH-111744 ( p 99m Tc-NC100692 uptake by pre-injecting the mice with excess unlabeled NC100692 reduced tumor uptake by approximately five-fold, to 0.68±0.3% ID/g ( p =0.01). Conclusion These results confirm that 99m Tc-NC100692 does, in fact, target the α v β 3 integrin and may, therefore, be useful in identifying patients prior to anti-α v β 3 therapy as well as monitoring the response of these patients to therapy.