Bi/At-Labeled MX35, an anti–sodium-dependent phosphate transport protein 2b (NaPi2b) murine monoclonal antibody

The sodium-dependent phosphate transporter NaPi2b is overexpressed in 70%–90% of ovarian cancers (1). Although NaPi2b is believed to maintain phosphate homeostasis in the human body, the exact role of this transporter in neoplastic transformation and ovarian cancer tumor growth is unclear. Investigators have developed a murine anti- NaPi2b monoclonal antibody (mAb), designated MX35, and showed that At-labeled MX35 ([At]MX35) can be used for the intraperitoneal radioimmunotherapy (RIT) of micrometastatic growth of OVCAR-3 cells (human ovarian cancer cells) in the peritoneum of nude mice (2). In a phase 1 study, the pharmacokinetics and dosimetry of the At-labeled MX35 F(ab') fragment were investigated in patients with ovarian cancer (3). From this study it was apparent that At (half-life, 7.2 h) is likely to irradiate other normal organs in the body by travelling through blood circulation (3, 4). In addition, it was reported that the efficacy of At reduces with the increase in lesion size because the radionuclide has a path length of 46–68 μm in the tissue (1, 3). In this regard, Bi appears to be a more suitable radionuclide for RIT of the ovarian cancer lesions because it has a short half-life (~46 min), a path length of 82 μm in the tissue, and probably does not travel to other organs because of its short half-life (3). As an extension of the earlier studies, the investigators labeled MX35 with Bi ([Bi]MX35) and compared its biodistribution with that of [At]MX35 in normal nude mice (3). It is pertinent to mention that Bi is transformed primarily to Po (half-life, 4.2 sec) which in turn decays to Pb (half-life, 3.2 h). There is a probability that the two nuclear transformations of Bi would occur during circulation and the final radionuclide (Pb) may not be retained on the chelating agent-mAb complex. Therefore, the biodistribution of the labeled mAb presented here may not be that of the mAb itself.