Exploration of peptide T7 and its derivative as integrin αvβ3-targeted imaging agents

OBJECTIVE: The aim of the present study was to develop potential candidates of integrin αvβ3-targeted imaging agent, which can facilitate the diagnosis and treatment of malignant solid tumors. METHODS: Peptides derived from tumstatin, named T7 and T7-6H, were derivatized to contain histidine in the C-terminus of their sequence and were labeled with (99m)Tc via nitrido and carbonyl precursors. The radiochemical purity and stability of (99m)Tc-labeled T7 and T7-6H were characterized by thin-layer chromatography. The whole body biodistribution was studied in NCI-H157-bearing BALB/c nude mice. RESULTS: The (99m)Tc-labeled T7 and T7-6H showed adequate in vitro stability, with a high radiochemical purity of over 90%. The dissociation constant (Kd) value of the (99m)Tc-labeled T7 and T7-6H ranged from 68.5 nM to 140.8 nM in U251 and NCI-H157 cell lines. (99m)Tc-labeled T7 and T7-6H showed no significant difference of biodistribution in mice. Furthermore, both T7 and T7-6H exhibited a poor blood–brain barrier penetration and a transient accumulation in lung; the uptake in tumor tissues was significantly higher than in muscle tissue, with a ratio of 5.8. CONCLUSION: (99m)Tc-labeled T7 and T7-6H can be regarded as promising single-photon emission computed tomography probes for imaging integrin αvβ3, and need to be further studied for noninvasive detection of tumors.