Integrin αvβ6-Targeted SPECT Imaging for Pancreatic Cancer Detection

lntegrin alpha(v)beta(6), a member of the integrin family, is specifically expressed in many malignancies but not in normal organs. Overexpression of integrin alpha(v)beta(6) is usually correlated with malignant potential and poor prognosis. In this study, we describe the synthesis and evaluation of a Tc-99m-labeled integrin alpha(v)beta(6)-targeting peptide as a SPECT radiotracer for the in vivo imaging of integrin alpha(v)beta(6) expression. Methods: An integrin alpha(v)beta(6)-targeting peptide (denoted as the HK peptide) was conjugated with 6-hydrazinonicotinyl (HYNIC) and radiolabeled with Tc-99m using tricine and TPPTS (trisodium triphenylphosphine-3,3',3 '' trisulfonate) as coligands. The in vitro and in vivo characteristics of Tc-99m-HYNIC(tricine)(TPPTS)-HK (Tc-99m-HHK) were investigated in BxPC-3 (integrin alpha(v)beta(6)-positive) and HEK293 (integrin alpha(v)beta(6)-negative) models. The ability of Tc-99m-HHK to detect liver metastasis of pancreatic cancer was evaluated using small-animal SPEC/CT. Results: Tc-99m-HHK showed high integrin alpha(v)beta(6)-binding specificity both in vitro and in vivo. Tc-99m-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 Tc-99m-HHK in BxPC-3 tumors was observed at 0.5 h after injection. High-contrast images of integrin alpha(v)beta(6)-positive tumors were obtained using Tc-99m-HHK. The minimum nonspecific activity accumulation in normal liver tissues rendered high-quality SPECT/CT images of metastatic lesions. Conclusion: Tc-99m-HHK is a promising SPECT radiotracer for the noninvasive imaging of integrin alpha(v)beta(6) expression in vivo. SPECT/ CT with Tc-99m-HHK could provide an effective approach for the noninvasive detection of primary and metastatic lesions of integrin alpha(v)beta(6)-positive tumors. a