Preliminary study on SPECT/CT imaging of pancreatic cancer xenografts by targeting integrin α5 in pancreatic stellate cells

Background: Integrin α5 (ITGA5) is overexpressed specifically in pancreatic cancer stroma, specially, in the activated pancreatic stellate cells (PSCs). Molecular imaging of pancreatic cancer via targeting PSCs has its advantages. Purpose: This study aims to investigate the feasibility of ITGA5-targeted SPECT/CT imaging of pancreatic cancer by targeting PSCs. Methods: ITGA5 expression in PSCs treated without or with pancreatic cancer SW1990 cells conditioned medium (SW1990-CM) was assessed by western blotting and immunofluorescence staining. ITGA5 specific inhibitor AV3 peptide was radiolabeled with (125)I to synthesize (125)I-AV3, and the labeling rate, in vitro stability and cellular uptake were further investigated. SW1990 cells alone or with PSCs were injected subcutaneously on the left and right lower limbs of nude mice respectively to establish pancreatic cancer xenograft model, and then (125)I-AV3 SPECT/CT imaging of pancreatic cancer-bearing nude mice was performed. The expression of ITGA5 in tumors was detected by immunohistochemical (IHC) staining. Results: (125)I-AV3 has an excellent labeling rate and good in vitro stability. After treated with SW1990-CM, PSCs had an increased expression of ITGA5 and higher (125)I-AV3 uptake. SPECT/CT imaging study showed that (125)I-AV3 was mainly accumulated in the right xenografts (co-injection of cancer cells and PSCs), while the left xenografts tumors have a poor imaging. Moreover, the uptake of radiotracer in both side tumors was inhibited significantly after the non-radiolabeled AV3 pretreatment. IHC staining showed that SW1990 + PSCs tumor has a higher positive rate of ITGA5 than SW1990 tumor. Conclusion: The preliminary study suggests that (125)I-AV3 can be used for SPECT/CT imaging of pancreatic cancer via targeting ITGA5 in PSCs, which is independent of the state of cancer cells and may have a special meaning.