99mTc-Labeled Tricarbonyl His-CNA35 as an Imaging Agent for the Detection of Tumor Vasculature

Journal of Nuclear Medicine

Nancy Van Damme¹  Gilles Mees¹  Magali Van Steenkiste¹  Chris Reutelingsperger¹  Simon Vermeire¹  Rudi Dierckx¹  Kathelijne Peremans¹  Koen Mertens¹  Christophe Van de Wiele¹  Yves D'Asseler¹ 

关键词: CNA35;    tricarbonyl;    tumor vasculature;    HT29;   

DOI  :  10.2967/jnumed.111.095794

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Given the importance of angiogenesis for a tumor's survival and growth, several therapeutic strategies rely on the selective inhibition of angiogenesis and the destruction of existing tumor vasculature. These strategies raise the need for a noninvasive tool to evaluate tumor vasculature. We describe the radiosynthesis and evaluation of an imaging tracer that specifically binds tumor subendothelial collagen and thereby images tumor vasculature. Methods: 99mTc-tricarbonyl was prepared and labeled with His–collagen-binding adhesion protein 35 (CNA35). After in vitro specificity testing, in vivo biodistribution and dosimetric studies were performed in healthy nude mice via planar imaging. 99mTc-(CO)3 His-CNA35 was evaluated for in vivo imaging of tumor vasculature in a HT29 colorectal carcinoma xenograft. Results: The labeling procedure yielded a compound with 95%–99% radiochemical purity and good in vitro stability. An in vitro binding test confirmed specificity and functionality. 99mTc-(CO)3 His-CNA35 rapidly cleared from the blood and predominantly accumulated in the kidneys and liver. The effective dose for a proposed single injection of 500 MBq of 99mTc-(CO)3 His-CNA35 is 3.70 mSv per organ or 2.01 mSv/g of tissue. Tumors were successfully visualized, and uptake correlated with ex vivo immunohistochemical staining of tumor vasculature. Conclusion: 99mTc-(CO)3 His-CNA35 may be a useful radioligand for the in vivo detection of tumor vasculature through subendothelial collagen binding. A noninvasive method of imaging tumor vasculature that could provide a reliable assessment of tumor vasculature would allow evaluation of the effectiveness of commonly used antiangiogenic therapies and determination of their optimal dosing and scheduling.

【 授权许可】

Unknown