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

Intravenously administered anti-tumor single-chain Fv (scFv) and diabody mo lecules exhibit rapid clearance kinetics and accumulation in tumors that ex press 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 C HX-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 emplo ying 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-21 3-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 determ ined by comparing the efficacy of treatment with 0.3 and 0.15 mu Ci doses o f 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-21 3 On both the C6.5K-A and NM3E2 scFvs resulted in similar anti-tumor effect s (p = 0.46) indicating that antigen-specific targeting was not a factor. T his suggests that the physical half-life of Bi-213 may be too brief to be e ffectively paired with systemically-administered diabody or scFv molecules. NUCL MED BIOL 27;4: 339-346, 2000. (C) 2000 Elsevier Science Inc. All righ ts reserved.