Construction and Preclinical Evaluation of a ^124/131I-Labeled Radiotracer for the Detection of Mesothelin-Overexpressing Cancer

Abstract

Mesothelin is a molecular biomarker of many types of solid cancers, which may represent a highly promising new target in the development of cancertargeted diagnostic agents. A human anti-mesothelin antibody with a low molecular weight, ET210sc, was applied; this antibody has potent affinity and can penetrate tissue quickly and stably without causing immunoreactions. We developed a new 124/131 I-labeled radiotracer of ET210sc. The 124/131 I-labeled ET210sc radiotracer showed excellent radiochemical quality (with over 99% radiolabeling yield, 0.07 GBq/μmol specific activity) and remarkable stability in phosphate-buffered saline (>95% at 3 days). The radiotracer retained its potent affinity (dissociation constant, K d = 0.101 nM). The radiotracer specifically bound to mesothelin-positive cells in vitro. Interestingly, the radiotracer exhibited significant positive-tonegative tumor uptake ratios (1.5:1) 3 days postinjection. The estimated absorbed doses of each organ (e.g., 0.704 mGy/MBq for the rectum; 0.341 mGy/MBq for the spleen) met the medical safety standards for further clinical applications. Our findings provide an initial proof of concept for the potential use of 124/131 I-labeled ET210sc radiotracers to detect mesothelin-overexpressing cancer. 124 I-ET210sc is proposed to be an ideal imaging agent for further clinical applications.

Construction of a 124I-Labeled Specific Antibody for the Noninvasive Detection of Mesothelin-Overexpressing Tumors

“…31 Wang used 124/131 I to label and image the MSLN antibody fragment (scFv-Fc) ET210sc and detected high uptake of the probe in MSLN-overexpressing tumors. 32 By comparing 124 I-anti-MSLN with 124 I-ET210sc, we found that the PET/CT images of 124 I-anti-MSLN (7.4 MBq) were better than those of 124 I-ET210sc (11.1 MBq). The T/M value of 124 I-anti-MSLN (10.56 ± 1.12) was higher than that of 124 I-ET210sc (6.11 ± 2.18) 3 days postinjection.…”

“…Weele used TFP-N-sucDf to conjugate AMA to label 89 Zr, and the results showed that it is possible to noninvasively observe human pancreatic tumors subcutaneously implanted in mice with 89 Zr-AMA . Wang used 124/131 I to label and image the MSLN antibody fragment (scFv-Fc) ET210sc and detected high uptake of the probe in MSLN-overexpressing tumors . By comparing 124 I-anti-MSLN with 124 I-ET210sc, we found that the PET/CT images of 124 I-anti-MSLN (7.4 MBq) were better than those of 124 I-ET210sc (11.1 MBq).…”