SPECT/CT imaging of pancreatic cancer xenografts by targeting integrin α5 (ITGA5) in pancreatic stellate cells

1051 Objectives: Integrin α5 (ITGA5) is specifically expressed in pancreatic cancer stroma and activated pancreatic stellate cells (PSCs). In this study, we try to investigate the feasibility of SPECT imaging of pancreatic cancer by targeting ITGA5. Methods: The specific inhibitor of ITGA5, AV3 peptide (RYYRITY), which contains three tyrosine residues, meaning it is suitable for radioiodine labeling, was directly radiolabeled with 125I using the Iodogen method. The labeling rate and in vitro stability of 125I-AV3 in PBS and 10% FBS were tested. For the pancreatic cancer animal model, pancreatic cancer cells or “pancreatic cancer cells + PSCs” were injected subcutaneously on the left and right lower limbs respectively in the same nude mouce. SPECT/CT imaging of pancreatic cancer xenografts in nude mice was performed at different time points after the intravenous injection of 125I-AV3, and for the blocking experiment, an excessive dose of non-radiolabeled AV3 was injected and then the imaging was carried out. Results: The synthesized 125I-AV3 has a high labeling rate, which exceed 97% and can be used directly. After 12 h, thee radiochemical purity of 125I-AV3 was 91%, 82% in PBS and 10% FBS, respectively, suggesting a good in vitro stability. In the animal experiment, the volume of pancreatic cancer xenografts on the right limbs (coinjection of pancreatic cancer cells and PSCs) was bigger than that on the left limbs. According to the results of SPECT/CT inaging, 125I-AV3 was accumulated mainly in the right xenografts, and the uptake of radiotracer in both side tumors was attenuated significantly after the nonlabeled AV3 pretreatment. Conclusions: 125I-AV3 SPECT imaging can be used for the detection of pancreatic cancer by targeting ITGA5 in activated PSCs, which is independ on the status of pancreatic cancer cells.