Abstract A016: Novel positron emission tomography imaging targeting cell surface glycans for pancreatic cancer: 18F-labeled rBC2LCN lectin
Authors: Kuroda Yukihito , Oda Tatsuya , Shimomura Osamu , Mathis Bryan J. , Tateno Hiroaki , Hatano Kentaro 
Published: January 2024

Abstract
Introduction: Advancement in early detection modalities will greatly improve the overall prognoses of pancreatic ductal adenocarcinoma (PDAC). As a molecular imaging technique, [18F]FDG-PET imaging has provided new insight in PDAC diagnosis; however, the utility of FDG for early-stage PDAC detection remains undefined. Therefore, PET radiotracers conjugated to malignancy-specific targeting agents (e.g., antibodies targeting cancer-associated/specific antigens) have been developed to improve specificity toward cancer cells but persist in the developmental stage. One underexplored cancer cell surface-specific target is the glycocalyx. We have previously demonstrated that fucosylated glycans (H type-3 antigens) are expressed in pancreatic cancers and a recombinant lectin, rBC2LCN, binds to these glycans specifically (Shimomura O et al: Mol Cancer Ther 2018). Here, we developed a novel, lectin-based PET probe targeting cell surface glycan for pancreatic cancer. Material and Methods: The rBC2LCN (16kDa) lectin was labeled with N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB), prepared according to literature (Maeding P, et al: Appl Radiat Isot 2005) in phosphate buffer (pH 8.5). Obtained [18F]FB-rBC2LCN was then purified using gel filtration column (PD-10, GE, Uppsala, Sweden). A PDAC cell line, Capan-1, was used as a model which expresses H type-3 antigens. The biodistribution of the [18F]FB-rBC2LCN was evaluated in athymic nude mice bearing subcutaneous Capan-1 tumors. Static, small-animal PET imaging studies (G4, SOFIE, Dulles, VA) were performed to further evaluate in vivo tumor targeting and specificity. Results: The decay-corrected radiochemical mean yield of [18F]FB-rBC2LCN was 3.6%±0.3% (mean±SD), based on [18F]SFB, and radiochemical purity was above 95%. Cell binding and uptake revealed that [18F]FB-rBC2LCN binds to Capan-1 cells. Mice received 0.32±0.16 MBq (corresponding to 59±21 mg) of product, injected intravenously. Biodistribution studies demonstrated that Capan-1 tumor uptake (6.5±2.0 %ID/g) was high as early as 60 min after injection of [18F]FB-rBC2LCN and the uptake increased over time (9.6±2.2 and 11±3.9 at 150 and 240 min after injection, respectively). Tumor-to-muscle ratio increased with time up to 19±1.8 at 360 min after injection, indicating image contrast. Although kidneys (72±23 %ID/g), liver (7.1±1.7 %ID/g) and lungs (7.4±2.9 %ID/g) showed high uptake at 60 min after injection, the uptake of those organs decreased over time. The blood activity concentration of the tracer was also high at 60 min after injection (12±4.4 %ID/g) and decreased over time. Bone uptake was very low (below 1.8 %ID/g throughout the study), indicating that defluorinating metabolism was negligible. High-contrast PET imaging of tumors was achieved as early as 60 min after injection and the contrast became clearer over 240 min, consistent with the biodistribution result. Conclusions: Our 18F-labeled rBC2LCN lectin warrants further clinical development to improve the accuracy and sensitivity of early-stage PDAC detection.
Citation Format: Yukihito Kuroda, Tatsuya Oda, Osamu Shimomura, Bryan J. Mathis, Hiroaki Tateno, Kentaro Hatano. Novel positron emission tomography imaging targeting cell surface glycans for pancreatic cancer: 18F-labeled rBC2LCN lectin [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A016.