211At-MX35-F(ab’)2 is a radiolabeled antibody fragment developed and characterized at the Memorial Sloan-Kettering Cancer Center (MSKCC), New York, NY. MX35 is a murine IgG1-class monoclonal antibody directed toward a cell-surface glycoprotein of 95 kDa on OVCAR-3 cells. MX35 is expressed strongly and homogeneously on about 90% of human epithelial ovarian cancers. The labeled product is a potent therapeutic agent that is now used at several places in the frame of open clinical trials.

This molecule is used in ovarian cancer by intraperitoneal administration at a maximum dose per patient of 200 MBq (about 5 mCi). Further development intends to increase this amount.

In a Phase I study, the pharmacokinetics and dosimetry of the 211At-labeled MX35 F(ab’)2 fragment showed that 211At is likely to irradiate other normal organs in the body by travelling through the blood circulation. Furthermore, the efficacy of 211At reduces with the increase in lesion size because of the very short radionuclide path length. Developers considered 213Bi-MX35 and compared its biodistribution with that of 211At-MX35 in normal nude mice. Results were similar with an apparent higher efficacy for the 211At-labeled compound. 213Bi-MX35 was not pursued in human trials.

The Phase I study indicated that by intraperitoneal administration of 211At-MX35 F(ab’)2 it is possible to achieve therapeutic absorbed doses in microscopic tumor clusters without significant toxicity. 211At-MX35-F(ab’)2 is presently used in the frame of an open clinical trial in both Copenhagen, Denmark (about 50 patients per year) and in Gothenburg, Sweden (300 to 400 patients per year) for the treatment of ovarian cancer. There is no fund available for a full development of this drug.

Target/Mechanism: OVCAR-3

Leading Emitter: alpha particle (α)