Novel positron emission tomography imaging targeting cell surface glycans for pancreatic cancer: 18F‐labeled rBC2LCN lectin

Advancement in early detection modalities will greatly improve the overall prognoses of pancreatic ductal adenocarcinoma (PDAC). For this purpose, we report a novel class of tumor‐specific probes for positron emission tomography (PET) based on targeting cell surface glycans. The PDAC‐targeting ability of rBC2LCN lectin, combined with fluorine‐18 (18F) ([18F]FB‐rBC2LCN), resulted in reproducible, high‐contrast PET imaging of tumors in a PDAC xenograft mouse model. [18F]N‐succinimidyl‐4‐fluorobenzoate ([18F]SFB) was conjugated to rBC2LCN, and [18F]FB‐rBC2LCN was successfully prepared with a radiochemical purity >95%. Cell binding and uptake revealed that [18F]FB‐rBC2LCN binds to H‐type‐3‐positive Capan‐1 pancreatic cancer cells. As early as 60 min after [18F]FB‐rBC2LCN (0.34 ± 0.15 MBq) injection into the tail vein of nude mice subcutaneously bearing Capan‐1 tumors, tumor uptake was high (6.6 ± 1.8 %ID/g), and the uptake increased over time (8.8 ± 1.9 %ID/g and 11 ± 3.2 %ID/g at 150 and 240 min after injection, respectively). Tumor‐to‐muscle ratios increased over time, up to 19 ± 1.8 at 360 min. High‐contrast PET imaging of tumors relative to background muscle was also achieved as early as 60 min after injection of [18F]FB‐rBC2LCN (0.66 ± 0.12 MBq) and continued to increase up to 240 min. Our 18F‐labeled rBC2LCN lectin warrants further clinical development to improve the accuracy and sensitivity of early‐stage pancreatic cancer detection. In this study, we generated an engineered, 18F‐labeled rBC2LCN lectin, [18F]FB‐rBC2LCN, to target cell surface glycans differentially upregulated in pancreatic cancer. In our pancreatic cancer cell xenograft model, [18F]FB‐rBC2LCN reproducibly yielded high‐contrast positron emission tomography (PET) imaging of tumors. Our 18F‐labeled rBC2LCN lectin warrants further clinical development to improve the accuracy and sensitivity of early‐stage detection of pancreatic cancer.