Radioimmunotherapy of a Human Lung Cancer Xenograft with Monoclonal Antibody RS7: Evaluation of 177Lu and Comparison of Its Efficacy with That of 90Y and Residualizing 131I

Journal of Nuclear Medicine

Heidi Richel¹  Rhona Stein¹  Susan Chen¹  Hans J. Hansen¹  David M. Goldenberg¹  Linda Reed¹  Serengulam V. Govindan¹  Gary L. Griffiths¹ 

[1] Garden State Cancer Center, Belleville; and Immunomedics, Inc., Morris Plains, New Jersey Garden State Cancer Center, Belleville; and Immunomedics, Inc., Morris Plains, New Jersey Garden State Cancer Center, Belleville; and Immunomedics, Inc., Morris Plains, New Jersey

关键词: ¹⁷⁷Lu;    ⁹⁰Y;    ¹³¹I;    residualizing labels;    radioimmunotherapy;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Tumor targeting and therapeutic efficacy of 177Lu-labeled monoclonal antibody (mAb) RS7 (antiepithelial glycoprotein-1) was evaluated in a human nonsmall cell lung carcinoma xenograft model. The potential of 177Lu-labeled RS7 was compared with that of RS7 labeled with 90Y and a residualizing form of 131I. Methods: A 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA) conjugate of RS7 was used for radiolabeling with 177Lu-acetate or 88/90Y-acetate. Biodistribution and therapy studies were conducted in nude mice with subcutaneous Calu-3 xenografts. Therapy studies were performed using the maximal tolerated doses (MTDs) of 90Y-DOTA-RS7 (3.9 MBq [105 μCi]) and 177Lu-DOTA-RS7 (10.2 MBq [275 μCi]) and compared with the data obtained using the MTD (13.0 MBq [350 μCi]) of a residualizing form of 131I-RS7. Results: Radiolabeling of RS7-DOTA conjugate with 177Lu-acetate was facile. 177Lu-DOTA-RS7 displayed biodistribution results that were nearly identical to that of the 88Y analog in a paired-label study. The mean percentage injected doses per gram (%ID/g) for 177Lu-RS7 and 88Y-RS7 (in parentheses) in tumor were 38.3 %ID/g (39.1 %ID/g), 63.0 %ID/g (66.0 %ID/g), 63.0 %ID/g (65.8 %ID/g), and 34.0 %ID/g (34.9 %ID/g) on days 1, 3, 7, and 14, respectively. Elimination of established tumors, with an initial mean tumor volume of 0.24 cm3, was shown using doses of 177Lu-DOTA-RS7 ranging from 5.6 to 9.3 MBq (150–250 μCi) per nude mouse, with no significant difference in response rate noted between the doses in this range. Specificity of the therapeutic effect was shown in an isotype-matched control experiment, in which 177Lu-DOTA-RS7 was markedly more effective than the 177Lu-DOTA control antibody. A comparison of the therapeutic efficacies of 177Lu-DOTA-RS7 and 90Y-DOTA-RS7, using mice with established tumors with an initial mean tumor volume of 0.85 cm3, indicated similar tumor growth inhibition and similar tumor regrowth profiles. The therapy data were similar to those obtained with residualizing 131I-RS7 obtained at the same time. Conclusion: 177Lu-RS7 is an effective radioimmunoconjugate for radioimmunotherapy. With its radiophysical properties similar to those of 131I, coupled with its facile and stable attachment to mAb, 177Lu promises to be an alternative to 131I, and a complement to 90Y, in radioimmunotherapy.

【 授权许可】

Unknown