astatine and Carcinoma

The aim of this preclinical study was to evaluate the characteristics of the monoclonal antibody Rebmab200, which is a humanized version of the ovarian-specific murine antibody MX35. This investigation contributes to the foundation for future clinical α-radioimmunotherapy of minimal residual ovarian cancer with 211At-Rebmab200. Here, the biodistribution of 211At-Rebmab200 was evaluated, as was the utility of 99mTc-Rebmab200 for bioimaging. Rebmab200 was directly compared with its murine counterpart MX35 in terms of its in-vitro capacity for binding the immobilized NaPi2B epitope and live cells; we also assessed its biodistribution in nude mice carrying subcutaneous OVCAR-3 tumors. Tumor antigen and cell binding were similar between Rebmab200 and murine MX35, as was biodistribution, including normal tissue uptake and in-vivo tumor binding. We also demonstrated that 99mTc-Rebmab200 can be used for single-photon emission computed tomography of subcutaneous ovarian carcinomas in tumor-bearing mice. Taken together, our data support the further development of Rebmab200 for radioimmunotherapy and diagnostics.

Topics: Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibody Affinity; Antibody Specificity; Antigens, Neoplasm; Antineoplastic Agents; Astatine; Carcinoma; Cell Line, Tumor; Female; Gene Expression; Humans; Mice; Mice, Nude; Ovarian Neoplasms; Radioimmunotherapy; Radiopharmaceuticals; Sodium-Phosphate Cotransporter Proteins, Type IIb; Technetium; Tissue Distribution; Tomography, Emission-Computed, Single-Photon; Xenograft Model Antitumor Assays

The humanized antibody A33 binds to the A33 antigen, expressed in 95% of primary and metastatic colorectal carcinomas. The restricted pattern of expression in normal tissue makes this antigen a possible target for radioimmunotherapy of colorectal micrometastases. In this study, the A33 antibody was labeled with the therapeutic nuclide (211)At using N-succinimidyl para-(tri-methylstannyl)benzoate (SPMB). The in vitro characteristics of the (211)At-benzoate-A33 conjugate ((211)At-A33) were investigated and found to be similar to those of (125)I-benzoate-A33 ((125)I-A33) in different assays. Both conjugates bound with high affinity to SW1222 cells (K(d) = 1.7 +/- 0.2 nM, and 1.8 +/- 0.1 nM for (211)At-A33 and (125)I-A33, respectively), and both showed good intracellular retention (70% of the radioactivity was still cell associated after 20 hours). The cytotoxic effect of (211)At-A33 was also confirmed. After incubation with (211)At-A33, SW1222 cells had a survival of approximately 0.3% when exposed to some 150 decays per cell (DPC). The cytotoxic effect was found to be dose-dependent, as cells exposed to only 56 DPC had a survival of approximately 5%. The (211)At-A33 conjugate shows promise as a potential radioimmunotherapy agent for treatment of micrometastases originating from colorectal carcinoma.

Topics: Antibodies, Monoclonal; Antibodies, Neoplasm; Antigens, Neoplasm; Astatine; Carcinoma; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colonic Neoplasms; Colorectal Neoplasms; Dose-Response Relationship, Drug; Humans; Immunoglobulins; In Vitro Techniques; Membrane Glycoproteins; Neoplasm Metastasis; Protein Binding; Radioimmunotherapy; Time Factors

The concentrations of 211At and 125I were measured in various tissues in nude mice bearing xenografts of human thyroid tissue (fetal and malignant). The relative concentration of the two halogens was obtained at 4 and 24 h after injection. Samples were taken of the host blood, muscle and thyroid gland and the grafted tissues. The mouse thyroid concentrated 125I more efficiently than 211At but the human grafts concentrated both halogens about equally.

Topics: Adenocarcinoma; Animals; Astatine; Autoradiography; Carcinoma; Fetus; Humans; Injections, Intraperitoneal; Iodine Radioisotopes; Male; Mice; Mice, Nude; Thyroid Gland; Thyroid Neoplasms

Topics: Adenofibroma; Animals; Astatine; Carcinoma; Female; Growth; Mammary Neoplasms, Experimental; Mathematics; Neoplasms, Radiation-Induced; Radioisotopes; Rats