Cooperative Effect of Radioimmunotherapy and Antiangiogenic Therapy with Thalidomide in Human Cancer Xenografts

Journal of Nuclear Medicine

Atsuhiro Kawashima¹  Naoto Watanabe¹  Norihisa Tonami¹  Hisashi Bunko¹  Kunihiko Yokoyama¹  Seigo Kinuya¹  Shota Konishi¹  Kiyoshi Koshida¹  Takatoshi Michigishi¹  Noriyuki Shuke¹ 

关键词: radioimmunotherapy;    antiangiogenic therapy;    thalidomide;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Antiangiogenic therapy may prolong the dormancy of cancer lesions. Moreover, radioimmunotherapy (RIT) may eradicate this population of cells. This study dealt with determining the benefits associated with the combined usefulness of these 2 therapies with respect to inhibition of tumor growth. Methods: Antiangiogenic therapy using oral thalidomide (daily dose, 200 mg/kg) and RIT involving a single intravenous injection (4.63 MBq 131I-A7, an IgG1 murine monoclonal antibody) were conducted in mice bearing LS180 human colon cancer xenografts. RIT with an irrelevant IgG1, HPMS-1, was also performed as a control. Antiangiogenesis of thalidomide was investigated by immunohistochemical analysis of tumor sections. Results: Antiangiogenic therapy and RIT with 131I-A7 significantly suppressed the growth of xenografts. This combination produced more efficient tumor growth inhibition than did the monotherapy (P < 0.005). RIT using 131I-HPMS-1 was far less effective than 131I-A7, even when combined with thalidomide administration. Immunohistochemistry revealed a decrease in the microvessel number within tumors treated with thalidomide (P < 0.0001). Combined therapy further reduced the microvessel number (P < 0.01 vs. thalidomide monotherapy). Conclusion: The combination of RIT and thalidomide antiangiogenic therapy produces a better response of tumors than does monotherapy. Acting in concert, antiangiogenic therapy may prolong the dormancy of cancer lesions and RIT may eradicate this population of cells.

【 授权许可】

Unknown