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 (F-18) ([F-18] FB-rBC2LCN), resulted in reproducible, high-contrast PET imaging of tumors in a PDAC xenograft mouse model. [F-18]N-succinimidyl-4-fluorobenzoate ([F-18]SFB) was conjugated to rBC2LCN, and [F-18]FB-rBC2LCN was successfully prepared with a radiochemical purity >95%. Cell binding and uptake revealed that [F-18]FB-rBC2LCN binds to H-type-3--positive Capan-1 pancreatic cancer cells. As early as 60 min after [F-18]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 [F-18]FB--rBC2LCN (0.66 +/- 0.12 MBq) and continued to increase up to 240 min. Our F-18-labeled rBC2LCN lectin warrants further clinical development to improve the accuracy and sensitivity of early--stage pancreatic cancer detection.