Preclinical evaluation of monoclonal antibody 14C5 for targeting pancreatic cancer
Faculty of Medicine and Health Sciences
Cancer biotherapy and radiopharmaceuticals. - New York
, p. 193-205
The use of radiolabeled antibodies that are able to target primary tumors as well as metastatic tumor sites with minimal reactivity to normal tissues is a promising approach for treating pancreatic cancer. In this study, the integrin αvß5 is studied as a target for the diagnosis of and potential therapy for human pancreatic cancer by using the radiolabeled murine monoclonal antibody (mAb) 14C5. Biopsy specimens from human pancreatic tumors were examined for the expression of the integrin αvß5. The pancreatic tumor cell line Capan-1 was used to test the in vitro targeting potency of mAb 14C5 labeled with 125/131-iodine and 111-indium. Internalization, retention, and metabolism were investigated in cellular radioimmunoassays. Biodistribution and tumor-targeting characteristics were studied in Capan-1 xenografts. All tumor sections were positive for the integrin αvß5, with an extensive positive staining of the stroma. Saturation binding experiments showed high affinity with comparable Kds. In vitro internalization experiments showed a longer intracellular retention of 111In-p-benzyl isothiocyanate-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (p-SCN-Bz-DOTA)-14C5 in comparison to 125I-14C5 and 111In-p-isothiocyanatobenzyl diethylenetriaminepentaacetic acid (p-SCN-Bz-DTPA)-14C5. In vivo radioisotope tumor uptake was maximum at 4872 hours, with the uptake of 111In-p-SCN-Bz-DOTA-14C5 (35.84 ± 8.64 percentage of injected dose per g [%ID/g]) being 3.9- and 2.2-folds higher than 131I-14C5 (12.16 ± 1.03%ID/g) and 111In-p-SCN-Bz-DTPA-14C5 (14.30 ± 3.76%ID/g), respectively. Planar gamma imaging with mAb 14C5 indicated clear localization of the pancreatic tumors versus minimal normal tissue uptake. mAb 14C5 is a promising new antibody for targeting the integrin αvß5 for the diagnosis of and potential therapy for pancreatic cancer.