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Integrin αvβ6 is expressed at an undetectable level in normal tissues, but is remarkably upregulated during many pathological processes, especially in cancer and fibrosis. Noninvasive imaging of integrin αvβ6 expression using a radiotracer with favorable in vivo pharmacokinetics would facilitate disease diagnosis and therapy monitoring. Through disulfide-cyclized method, we synthesized in this study, a new integrin αvβ6-targeted cyclic peptide (denoted as cHK), and radiolabeled it with 99m Tc. The ability of the resulting radiotracer 99m Tc-HYNIC-cHK to detect integrin αvβ6 expression in pancreatic cancer xenografts and idiopathic pulmonary fibrosis was evaluated using small-animal single-photon emission computed tomography (SPECT)/computed tomography (CT). 99m Tc-HYNIC-cHK showed significantly improved in vivo metabolic stability compared to the linear peptide-based radiotracer 99m Tc-HYNIC-HK. 99m Tc-HYNIC-cHK exhibited similar biodistribution properties to 99m Tc-HYNIC-HK, but the tumor-to-muscle ratio was significantly increased (2.99 ± 0.87 vs. 1.82 ± 0.27, P  &lt; 0.05). High-contrast images of integrin αvβ6-positive tumors and bleomycin-induced fibrotic lungs were obtained by SPECT/CT imaging using 99m Tc-HYNIC-cHK. Overall, our studies demonstrate that 99m Tc-HYNIC-cHK is a promising SPECT radiotracer for the noninvasive imaging of integrin αvβ6 in living subjects.

biophysics reports

Small-animal SPECT/CT imaging of cancer xenografts and pulmonary fibrosis using a 99mTc-labeled integrin αvβ6-targeting cyclic peptide with improved in vivo stability