Abstract 4206: A dual-motif CAIX inhibitor, [64Cu]XYIMSR-06, for PET imaging of clear cell renal cell carcinoma

• Published in: Cancer research (Chicago, Ill.) Ill.), 2016-07, Vol.76 (14_Supplement), p.4206-4206
• Main Authors: MINN, IL, Koo, Soo Min, Lee, Hye Soo, Brummet, Mary, Rowe, Steven P., Gorin, Michael A., Sysa-Shah, Polina, Lewis, William D., Ahn, Hye-Hyun, Wang, Yuchuan, Ray, Sangeeta, Mease, Ronnie C., Nimmagadda, Sridhar, Allaf, Mohamad E., Pomper, Martin G., Yang, Xing
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2016-4206

Carbonic anhydrase IX (CAIX) is a cell surface enzyme that is over-expressed in approximately 95% of clear cell renal cell carcinomas (ccRCCs), the most common renal cancer. CAIX is also a surrogate marker of hypoxic tumors for various human cancers; however, a clinically viable molecular imaging agent targeting CAIX is not available. We have synthesized and performed in vitro and in vivo evaluation of a dual-motif, low-molecular-weight inhibitor of CAIX, [64Cu] XYIMSR-06, for imaging CAIX expression on ccRCC tumors using positron emission tomography (PET). [64Cu] XYIMSR-06 was synthesized in two steps from reported dual-motif precursor 1. Upon radiolabeling, [64Cu] XYIMSR-06 was evaluated in immunocompromised mice bearing CAIX-expressing SK-RC-52 tumors for in vivo PET imaging and biodistribution. [64Cu] XYIMSR-06 was generated in radiochemical yields of 51.0 ± 4.5% (n = 5) and specific radioactivity of 6.0 GBq/μmol (170Ci/mmol ± 70, n = 5). Tumor could be visualized on PET images by 1 h post-injection with high tumor-to-background levels achieved within 24 h. Biodistribution studies of [64Cu] XYIMSR-06 demonstrated a maximum tumor uptake of 19.3 ± 4.51% injected dose per gram of radioactivity at 4 h. Tumor-to- blood, muscle and kidney ratios were 129.6 ± 18.8, 84.3 ± 21.0 and 2.1 ± 0.26, respectively, at 8 h post-injection. At 24 h, a tumor-to-kidney ratio of 7.1±2.5 was achieved. These findings represent increased tumor-to-background ratios at the indicated times relative to previously reported CAIX-targeted imaging agents. [64Cu] XYIMSR-06 is a promising candidate for PET imaging of CAIX expressing tumors, especially ccRCC. Citation Format: IL MINN, Soo Min Koo, Hye Soo Lee, Mary Brummet, Steven P. Rowe, Michael A. Gorin, Polina Sysa-Shah, William D. Lewis, Hye-Hyun Ahn, Yuchuan Wang, Sangeeta Ray, Ronnie C. Mease, Sridhar Nimmagadda, Mohamad E. Allaf, Martin G. Pomper, Xing Yang. A dual-motif CAIX inhibitor, [64Cu]XYIMSR-06, for PET imaging of clear cell renal cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4206.