Dual Targeting of Integrin α v β 3 and Neuropilin-1 Receptors Improves Micropositron Emission Tomography Imaging of Breast Cancer.

The receptors neuropilin-1 (NRP-1) and integrin α v β 3 are overexpressed in breast cancer and associated with neovascularization. We synthesized a heterodimeric tracer, 68 Ga-DOTA-RGD-ATWLPPR, which simultaneously targets integrin α v β 3 and NRP-1 in breast cancer. In this study, we evaluated the diagnostic efficacy of 68 Ga-DOTA-RGD-ATWLPPR during micropositron emission tomography (microPET)/X-ray computed tomography (CT) imaging and gamma counting. We evaluated the receptor-binding characteristics and tumor-targeting efficacy of the tracer in vitro and in vivo . Static microPET/CT imaging and gamma counting studies showed that 68 Ga-DOTA-RGD-ATWLPPR uptake in MCF-7 tumors is higher than that of monomeric tracers. 68 Ga-DOTA-RGD-ATWLPPR uptake could be blocked with excess unlabeled RGD or ATWLPPR, demonstrating the sensitivity and specificity of the tracer. We did not observe bone tracer uptake in vivo , but the data indicated that 68 Ga-DOTA-RGD-ATWLPPR is metabolized in the kidneys and the liver uptake is low. In conclusion, 68 Ga-DOTA-RGD-ATWLPPR has improved binding affinity, targeting efficiency, and tumor retention time when compared to monomeric tracers, suggesting that it has potential as an imaging probe for breast cancer detection.