PT  - JOURNAL ARTICLE
AU  - Mees, Gilles
AU  - Dierckx, Rudi
AU  - Mertens, Koen
AU  - Vermeire, Simon
AU  - Van Steenkiste, Magali
AU  - Reutelingsperger, Chris
AU  - D'Asseler, Yves
AU  - Peremans, Kathelijne
AU  - Van Damme, Nancy
AU  - Van de Wiele, Christophe
TI  - <sup>99m</sup>Tc-Labeled Tricarbonyl His-CNA35 as an Imaging Agent for the Detection of Tumor Vasculature
AID  - 10.2967/jnumed.111.095794
DP  - 2012 Mar 01
TA  - Journal of Nuclear Medicine
PG  - 464--471
VI  - 53
IP  - 3
4099  - http://jnm.snmjournals.org/content/53/3/464.short
4100  - http://jnm.snmjournals.org/content/53/3/464.full
SO  - J Nucl Med2012 Mar 01; 53
AB  - 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.