Integrin α_vβ₆–Targeted SPECT Imaging for Pancreatic Cancer Detection

Abstract

Integrin α_vβ₆, a member of the integrin family, is specifically expressed in many malignancies but not in normal organs. Overexpression of integrin α_vβ₆ is usually correlated with malignant potential and poor prognosis. In this study, we describe the synthesis and evaluation of a ^99mTc-labeled integrin α_vβ₆–targeting peptide as a SPECT radiotracer for the in vivo imaging of integrin α_vβ₆ expression. <b>Methods:</b> An integrin α_vβ₆–targeting peptide (denoted as the HK peptide) was conjugated with 6-hydrazinonicotinyl (HYNIC) and radiolabeled with ^99mTc using tricine and TPPTS (trisodium triphenylphosphine-3,3′,3″-trisulfonate) as coligands. The in vitro and in vivo characteristics of ^99mTc-HYNIC(tricine)(TPPTS)-HK (^99mTc-HHK) were investigated in BxPC-3 (integrin α_vβ₆–positive) and HEK293 (integrin α_vβ₆–negative) models. The ability of ^99mTc-HHK to detect liver metastasis of pancreatic cancer was evaluated using small-animal SPECT/CT. <b>Results:</b>^99mTc-HHK showed high integrin α_vβ₆–binding specificity both in vitro and in vivo. ^99mTc-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 ^99mTc-HHK in BxPC-3 tumors was observed at 0.5 h after injection. High-contrast images of integrin α_vβ₆–positive tumors were obtained using ^99mTc-HHK. The minimum nonspecific activity accumulation in normal liver tissues rendered high-quality SPECT/CT images of metastatic lesions. <b>Conclusion:</b>^99mTc-HHK is a promising SPECT radiotracer for the noninvasive imaging of integrin α_vβ₆ expression in vivo. SPECT/CT with ^99mTc-HHK could provide an effective approach for the noninvasive detection of primary and metastatic lesions of integrin α_vβ₆–positive tumors.