Integrin αvβ₆-Targeted SPECT Imaging for Pancreatic Cancer Detection.

UNLABELLED Integrin αvβ6, a member of the integrin family, is specifically expressed in many malignancies but not in normal organs. Overexpression of integrin αvβ6 is usually correlated with malignant potential and poor prognosis. In this study, we describe the synthesis and evaluation of a (99m)Tc-labeled integrin αvβ6-targeting peptide as a SPECT radiotracer for the in vivo imaging of integrin αvβ6 expression. METHODS An integrin αvβ6-targeting peptide (denoted as the HK peptide) was conjugated with 6-hydrazinonicotinyl (HYNIC) and radiolabeled with (99m)Tc using tricine and TPPTS (trisodium triphenylphosphine-3,3',3″-trisulfonate) as coligands. The in vitro and in vivo characteristics of (99m)Tc-HYNIC(tricine)(TPPTS)-HK ((99m)Tc-HHK) were investigated in BxPC-3 (integrin αvβ6-positive) and HEK293 (integrin αvβ6-negative) models. The ability of (99m)Tc-HHK to detect liver metastasis of pancreatic cancer was evaluated using small-animal SPECT/CT. RESULTS (99m)Tc-HHK showed high integrin αvβ6-binding specificity both in vitro and in vivo. (99m)Tc-HHK was cleared rapidly from the blood and normal organs except for the kidneys. The highest uptake (0.88 ± 0.12 percentage injected dose per gram) of (99m)Tc-HHK in BxPC-3 tumors was observed at 0.5 h after injection. High-contrast images of integrin αvβ6-positive tumors were obtained using (99m)Tc-HHK. The minimum nonspecific activity accumulation in normal liver tissues rendered high-quality SPECT/CT images of metastatic lesions. CONCLUSION (99m)Tc-HHK is a promising SPECT radiotracer for the noninvasive imaging of integrin αvβ6 expression in vivo. SPECT/CT with (99m)Tc-HHK could provide an effective approach for the noninvasive detection of primary and metastatic lesions of integrin αvβ6-positive tumors.