Imaging of bronchioloalveolar carcinoma in the mice with the αⅤβ3 integrin-targeted tracer (99m)Tc-RGD-4CK.

Receptor-based imaging agents have shown improved specificity and sensitivity of cancer diagnosis by targeting the specific features of cancer. Here we reported the (99m)Tc-labeling of a cyclic polypeptide RGD-4CK and the characterization of this agent in vitro and in bronchioloalveolar carcinoma (BAC) xenograft model. The αⅤβ3 integrin receptor binding affinity of (99m)Tc-RGD-4CK was determined in BAC. The cancer targeting properties of (99m)Tc-RGD-4CK were determined in NCI-H358 xenografted nude mice. Moreover, the BAC uptake of (99m)Tc-RGD-4CK was blocked with nonradiolabeled RGD-4CK in xenografts. The competitive assay showed that (99m)Tc-RGD-4CK exhibited high specificity to BAC cell line NCI-H358. Biodistribution studies indicated that (99m)Tc-RGD-4CK exhibited high tumor uptake (4.12 ± 1.21% injected dose/g 120 minutes after injection) and prolonged tumor retention (2.08 ± 0.33% injected dose/g 240 minutes after injection) in NCI-H358 xenografted nude mice. Moreover, (99m)Tc-RGD-4CK produced a good tumor-to-lung ratio (2.38) because of low lung activity accumulation 120 minutes postinjection. BAC on the flank of xenografted mice was clearly visualized by single photon emission computed tomography/computed tomography imaging using (99m)Tc-RGD-4CK. In conclusion, this study provides evidence that (99m)Tc-RGD-4CK is a promising agent for noninvasive determination of αⅤβ3 integrin status and therapy monitoring in BAC.