Imaging of bronchioloalveolar carcinoma in the mice with the αVβ3 integrin-targeted tracer 99mTc-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 Tc-99m-labeling of a cyclic polypeptide RGD-4CK and the characterization of this agent in vitro and in bronchioloalveolar carcinoma (BAC) xenograft model. The alpha(V)beta(3) integrin receptor binding affinity of Tc-99m-RGD-4CK was determined in BAC. The cancer targeting properties of Tc-99m-RGD-4CK were determined in NCI-H358 xenografted nude mice. Moreover, the BAC uptake of Tc-99m-RGD-4CK was blocked with nonradiolabeled RGD-4CK in xenografts. The competitive assay showed that Tc-99m-RGD-4CK exhibited high specificity to BAC cell line NCI-H358. Biodistribution studies indicated that Tc-99m-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, Tc-99m-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 Tc-99m-RGD-4CK. In conclusion, this study provides evidence that Tc-99m-RGD-4CK is a promising agent for noninvasive determination of alpha V beta(3) integrin status and therapy monitoring in BAC.