Comparison of Immunoscintigraphy, Efficacy, and Toxicity of Conventional and Pretargeted Radioimmunotherapy in CD20-Expressing Human Lymphoma Xenografts

Journal of Nuclear Medicine

Pat S. Stayton¹  Robert W. Mallett¹  Oliver W. Press¹  Don K. Hamlin¹  John M. Pagel¹  Krishnan Subbiah¹  Damon L. Meyer¹  D. Scott Wilbur¹  Don B. Axworthy¹  Louis J. Theodore¹ 

关键词: immunoscintigraphy;    CD20;    pretargeting;    streptavidin;    biotin;    lymphoma;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Pretargeted radioimmunotherapy (RIT) using streptavidin (sAv)-conjugated antibodies before radiolabeled-biotin is a promising approach to improve absorbed dose ratios and achieve high durable remission rates with diminished systemic toxicity. This study compared the immunoscintigraphy, toxicity, and therapeutic efficacy of pretargeted RIT with conventional RIT using an anti-CD20 antibody. Methods: Athymic mice bearing Ramos human Burkitt’s lymphoma xenografts were injected intraperitoneally with a 1F5-sAv conjugate followed 24 h later by a galactosylated, biotinylated clearing agent (CA) and, finally, 3 h later by 111In- or 90Y-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin. The comparison groups consisted of mice injected with conventional, directly labeled 111In- or 90Y-1F5. Results: Rapid tumor uptake of radioactivity within 2 h was observed with the pretargeting approach, resulting in high-contrast tumor images at 24 h with minimal blood-pool radioactivity. Although conventional radiolabeled antibodies produced clear tumor images at 24 h, a large amount of radioactivity was present in the blood pool. The tumor-to-blood ratio was 3.5:1 with pretargeting compared with 0.4:1 with conventional 111In-1F5. Pretargeted RIT with 29.6 MBq (800 μCi) 90Y-DOTA-biotin cured 100% of mice with tolerable toxicity, whereas conventional RIT with 90Y-1F5 at a dose of 14.8 MBq (400 μCi) produced no cures, induced profound pancytopenia, and was lethal to all mice. Conclusion: These results suggest that anti-CD20 pretargeted RIT may be superior to conventional radiolabeled antibodies in terms of radioimmunoscintigraphy, toxicity, and therapeutic efficacy for treatment of B-cell lymphomas.

【 授权许可】

Unknown