Photoimmunotherapy Targeting Prostate-Specific Membrane Antigen: Are Antibody Fragments as Effective as Antibodies?

Journal of Nuclear Medicine

Chang H. Paik¹  Tadanobu Nagaya¹  Toshiko Harada¹  Anna M. Wu¹  Hirofumi Hanaoka¹  Rira Watanabe¹  Makoto Mitsunaga¹  Hisataka Kobayashi¹  Insook Kim¹  Kazuhide Sato¹  Peter L. Choyke¹ 

关键词: photoimmunotherapy;    prostate specific membrane antigen;    monoclonal antibody;    diabody;    minibody;    pharmacokinetics;   

DOI  :  10.2967/jnumed.114.149526

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Photoimmunotherapy is a highly cell-selective cancer therapy based on an armed antibody conjugate with a phthalocyanine-based photosensitizer, IR700. Photoimmunotherapy induces rapid and highly specific necrosis in targeted cancer cells after exposure to near-infrared (NIR) light. Cells not expressing the antigen are not affected. To date, photoimmunotherapy has been demonstrated only with full antibody-IR700 conjugates. In this study, small and bivalent antibody fragments, including anti–prostate-specific membrane antigen (PSMA) diabody (Db) and minibody (Mb), were compared with intact IgG for their effectiveness as photoimmunotherapy agents. Methods: Radioiodinated antibody and antibody fragments with 125I were used to determine the timing of maximum binding of each anti-PSMA antibody fragment on the cell surface in vivo in mice bearing either PSMA-positive or -negative PC3 tumors. Then therapeutic efficacy of photoimmunotherapy was examined by exposing mice to NIR light at 2 time points based on the time of maximum cell surface binding at 6 h after injection for Db-IR700 and 24 h after injection for Mb-IR700 and IgG-IR700 as well as 24 h after the peak uptake times. Results: Photoimmunotherapy with the same molar concentration of PSMA-Db-IR700, PSMA-Mb-IR700, and PSMA-IgG-IR700 conjugate showed similar therapeutic effects in vitro and in vivo on PSMA-positive PC3 tumor xenografts in cytotoxicity and survival curves (P > 0.05). Conclusion: The use of PSMA-Db-IR700 conjugate results in the shortest time interval between injection and NIR exposure without compromising therapeutic effects of photoimmunotherapy.

【 授权许可】

Unknown