Talks
Presenting Author Academic/Professional Position
Faculty
Academic Level (Author 5)
Faculty
Discipline/Specialty (Author 5)
Immunology and Microbiology
Presentation Type
Oral Presentation
Discipline Track
Translational Science
Abstract Type
Research/Clinical
Abstract
Background: Colorectal cancer (CRC) remains one of the most diagnosed and deadliest forms of cancer worldwide. The high rate of encountered cases with distant metastatic presentation, a major contributor to CRC’s high mortality, presents a need for a molecular-based, selective strategy towards CRC treatment and management. To realize this, an antibody-based theranostic approach is under evaluation using a monoclonal antibody targeting the glycoprotein mucin 13 (MUC13), known for its aberrant expression, glycosylation patterns, and localization in CRC cells associated with tumorigenic properties. With tumor-specific uptake in high MUC13-expressing CRC xenografts previously reported in PET experiments after antibody labeling with positron-emitting zirconium-89 (89Zr), the therapeutic efficacy of this antibody-based approach is now studied using dual beta/Auger electron-emitting terbium-161 (161Tb) in a preclinical setting to indicate the potential for these two radiolabeled counterparts to comprise a theranostic regimen suitable for CRC treatment.
Methods: The MUC13-directed antibody C14 was conjugated with para-isothiocyanatobenzyl-1,4,7,10-tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA) followed by incubation with [161Tb]TbCl3 at a ratio of 437 kBq/µg (11.8 µCi/µg). Radiochemical purity (RCP) was determined by radio-thin layer chromatography (radio-TLC) and radio-size-exclusion chromatography (radio-SEC). Radiochemical yield (RCY) was measured using a well-type dose calibrator. CRC cell line-derived subcutaneous xenograft mouse models (T84, SNU-C4) with observed high MUC13 expression were utilized to evaluate biodistribution, maximum tolerated dose (MTD), antitumor efficacy, and survival benefit of [161Tb]Tb-DOTA-C14. MicroSPECT/CT was also performed to investigate tumor-specific accumulation of radioimmunoconjugate in vivo. Results were compared to those acquired with a C14-based analog immunoconjugate radiolabeled with 89Zr to determine their suitability as theranostic partners.
Results: Radiolabeling efforts produced [161Tb]Tb-DOTA-C14 with RCP >95% and RCY of 88% (n.d.c.). Ex vivo biodistribution measurements demonstrated consistent accumulation of 161Tb-labeled C14 in T84 tumor tissue over 6 days (4.8±0.6 %ID/g at 24 h p.i., 7.4±0.8 %ID/g at 144 h p.i.) with gradual clearance observed in blood and non-target organs at levels similar to those recorded with 89Zr-labeled C14. By varying the radioimmunoconjugate dose, it was observed that activities ≤7.4 MBq (200 µCi) did not lead to significant weight loss or acute radiation toxicity. A single injection of 7.4 MBq (200 µCi) [161Tb]Tb-DOTA-C14 into mice bearing either T84 or SNU-C4 xenografts resulted in tumor growth delay with significant differences noted in comparison to a non-treatment cohort (ex: p161Tb]Tb-DOTA-C14 in both xenograft models compared to non-treated mice (p161Tb-labeled C14 was visualized with microSPECT up to 6 days post-treatment with minimal background signal, comparable to PET images collected using 89Zr-labeled C14.
Conclusions: CRC-associated MUC13 expression was evaluated as a target for radioimmunotherapy using 161Tb-labeled C14 with promising results indicating antitumor efficacy and increased survival with reduced radioactivity uptake in non-target sites as observed in both ex vivo measurements and in vivo nuclear imaging. These results also demonstrate compatibility with those collected using 89Zr-labeled C14, indicating a promising theranostic pair for complementary imaging and treatment of CRC currently under further investigation.
Recommended Citation
Coll, Ryan P.; Yamaguchi, Aiko; Wang, Jianbo; Ta, Robert T.; Chauhan, Subhash C.; and Manning, H. Charles, "Evaluation of mucin 13 expression as a target for radioimmunotherapy: One step closer to a radionuclide theranostic strategy for colorectal cancer" (2025). Research Symposium. 26.
https://scholarworks.utrgv.edu/somrs/2025/talks/26
Included in
Evaluation of mucin 13 expression as a target for radioimmunotherapy: One step closer to a radionuclide theranostic strategy for colorectal cancer
Background: Colorectal cancer (CRC) remains one of the most diagnosed and deadliest forms of cancer worldwide. The high rate of encountered cases with distant metastatic presentation, a major contributor to CRC’s high mortality, presents a need for a molecular-based, selective strategy towards CRC treatment and management. To realize this, an antibody-based theranostic approach is under evaluation using a monoclonal antibody targeting the glycoprotein mucin 13 (MUC13), known for its aberrant expression, glycosylation patterns, and localization in CRC cells associated with tumorigenic properties. With tumor-specific uptake in high MUC13-expressing CRC xenografts previously reported in PET experiments after antibody labeling with positron-emitting zirconium-89 (89Zr), the therapeutic efficacy of this antibody-based approach is now studied using dual beta/Auger electron-emitting terbium-161 (161Tb) in a preclinical setting to indicate the potential for these two radiolabeled counterparts to comprise a theranostic regimen suitable for CRC treatment.
Methods: The MUC13-directed antibody C14 was conjugated with para-isothiocyanatobenzyl-1,4,7,10-tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA) followed by incubation with [161Tb]TbCl3 at a ratio of 437 kBq/µg (11.8 µCi/µg). Radiochemical purity (RCP) was determined by radio-thin layer chromatography (radio-TLC) and radio-size-exclusion chromatography (radio-SEC). Radiochemical yield (RCY) was measured using a well-type dose calibrator. CRC cell line-derived subcutaneous xenograft mouse models (T84, SNU-C4) with observed high MUC13 expression were utilized to evaluate biodistribution, maximum tolerated dose (MTD), antitumor efficacy, and survival benefit of [161Tb]Tb-DOTA-C14. MicroSPECT/CT was also performed to investigate tumor-specific accumulation of radioimmunoconjugate in vivo. Results were compared to those acquired with a C14-based analog immunoconjugate radiolabeled with 89Zr to determine their suitability as theranostic partners.
Results: Radiolabeling efforts produced [161Tb]Tb-DOTA-C14 with RCP >95% and RCY of 88% (n.d.c.). Ex vivo biodistribution measurements demonstrated consistent accumulation of 161Tb-labeled C14 in T84 tumor tissue over 6 days (4.8±0.6 %ID/g at 24 h p.i., 7.4±0.8 %ID/g at 144 h p.i.) with gradual clearance observed in blood and non-target organs at levels similar to those recorded with 89Zr-labeled C14. By varying the radioimmunoconjugate dose, it was observed that activities ≤7.4 MBq (200 µCi) did not lead to significant weight loss or acute radiation toxicity. A single injection of 7.4 MBq (200 µCi) [161Tb]Tb-DOTA-C14 into mice bearing either T84 or SNU-C4 xenografts resulted in tumor growth delay with significant differences noted in comparison to a non-treatment cohort (ex: p161Tb]Tb-DOTA-C14 in both xenograft models compared to non-treated mice (p161Tb-labeled C14 was visualized with microSPECT up to 6 days post-treatment with minimal background signal, comparable to PET images collected using 89Zr-labeled C14.
Conclusions: CRC-associated MUC13 expression was evaluated as a target for radioimmunotherapy using 161Tb-labeled C14 with promising results indicating antitumor efficacy and increased survival with reduced radioactivity uptake in non-target sites as observed in both ex vivo measurements and in vivo nuclear imaging. These results also demonstrate compatibility with those collected using 89Zr-labeled C14, indicating a promising theranostic pair for complementary imaging and treatment of CRC currently under further investigation.
