An Integrin-Alpha(V)Beta(6)/Alpha(5)Beta(1)-Bitargeted Probe For The Spect Imaging Of Pancreatic Adenocarcinoma In Preclinical And Primary Clinical Studies

Pancreatic adenocarcinoma (PA) is one of the deadliest human malignancies. However, early detection, prediction of surgical resectability, and prognosis of PA are challenging with current conventional imaging technologies in the clinic. Molecular imaging technologies combined with novel imaging probes could be useful for early detection and accurate staging of PA. Integrin alpha(v)beta(6) and alpha(5)beta(1) are found to be overexpressed in PA. In this study, integrin alpha(v)beta(6)/alpha(5)beta(1)-bitargeted probes Tc-99-HYNIC-isoDGR (Tc-99m-isoDGR) and Tc-99m-HYNIC-PEG(4)-PisoDGR2 (Tc-99m-3PisoDGR2) were prepared and evaluated in the BxPC-3 human pancreatic tumor model. Both subcutaneous and in situ BxPC-3 tumors could be clearly visualized by Tc-99m-isoDGR nanoScan SPECT/CT imaging with a high ratio of tumor to background. The blocking study with excess nonradioactive peptide showed a significantly reduced tumor uptake, which confirmed the specificity of Tc-99m-isoDGR. Biodistribution results confirmed the imaging results. The dimer tracer Tc-99m-3PisoDGR2 significantly enhanced tumor uptake compared with Tc-99m-isoDGR, and the spontaneous PA lesion in the mouse model could be clearly visualized by Tc-99m-3PisoDGR2. The primary clinical study also verified the ability of Tc-99m-3PisoDGR2 for detection of PA. Therefore, SPECT/CT imaging using the integrin alpha(v)beta(6)/alpha(5)beta(1)-bitargeted Tc-99m-3PisoDGR2 provided a potential approach for the noninvasive detection of PA.