Delivery of the α-emitting radioisotope bismuth-213 to solid tumors via single-chain Fv and diabody molecules

Intravenously administered anti-tumor single-chain Fv (scFv) and diabody molecules exhibit rapid clearance kinetics and accumulation in tumors that express their cognate antigen. In an attempt to fit the rate of isotope decay to the timing of delivery and duration of tumor retention, anti-HER2/neu CHX-A" DTPA-C6.5K-A scFv and diabody conjugates were labeled with the alpha-particle emitter Bi-213 (t(1/2) = 47 min). Radioimmunotherapy studies employing 0.64, 0.35, or 0.15 mu Ci of Bi-213-labeled C6.5K-A diabody or 1.1, 0.6, or 0.3 mu Ci of Bi-213-labeled C6.5K-A scFv were performed in nude mice bearing early, established SK-OV-3 rumors. Only the 0.3 mu Ci dose of Bi-213-labeled C6.5K-A scFv resulted in both acceptable toxicity and a reduction in tumor growth rate. The specificity of the anti-tumor effects was determined by comparing the efficacy of treatment with 0.3 and 0.15 mu Ci doses of Bi-213-labeled C6.5K-A scFv and Bi-213-labeled NM3E2 (an irrelevant scFv) in nude mice bearing large established tumors. The 0.3 mu Ci dose of Bi-213 On both the C6.5K-A and NM3E2 scFvs resulted in similar anti-tumor effects (p = 0.46) indicating that antigen-specific targeting was not a factor. This suggests that the physical half-life of Bi-213 may be too brief to be effectively paired with systemically-administered diabody or scFv molecules. NUCL MED BIOL 27;4: 339-346, 2000. (C) 2000 Elsevier Science Inc. All rights reserved.