[64Cu]XYIMSR-06: A dual-motif CAIX ligand for PET imaging of clear cell renal cell carcinoma
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Il Minn1, Soo Min Koo1, Hye Soo Lee1, Mary Brummet1, Steven P. Rowe1, Michael A. Gorin2, Polina Sysa-Shah1, William D. Lewis1, Hye-Hyun Ahn1, Yuchuan Wang1, Sangeeta Ray Banerjee1, Ronnie C. Mease1, Sridhar Nimmagadda1, Mohamad E. Allaf2, Martin G. Pomper1, Xing Yang1
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
2The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Martin G. Pomper, email: email@example.com
Xing Yang, email: firstname.lastname@example.org
Keywords: carbonic anhydrase IX, positron emission tomography, molecular imaging, renal cell carcinoma, copper-64
Received: February 25, 2016 Accepted: June 09, 2016 Published: July 14, 2016
Carbonic anhydrase IX (CAIX) is a cell surface enzyme that is over-expressed in approximately 95% of cases of clear cell renal cell carcinoma (ccRCC), the most common renal cancer. We synthesized and performed in vitro and in vivo evaluation of a dual-motif ligand, [64Cu]XYIMSR-06, for imaging CAIX expression on ccRCC tumors using positron emission tomography (PET). [64Cu]XYIMSR-06 was generated in yields of 51.0 ± 4.5% (n=5) and specific activities of 4.1 – 8.9 GBq/μmol (110-240 Ci/mmol). Tumor was visualized on PET images by 1 h post-injection with high tumor-to-background levels (>100 tumor-to-blood and -muscle) achieved within 24 h. Biodistribution studies demonstrated a maximum tumor uptake of 19.3% 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 ± 0.3, respectively, at 8 h post-injection. At 24 h a tumor-to-kidney ratio of 7.1 ± 2.5 was achieved. These results indicate pharmacokinetics superior to those of previously reported imaging agents binding to CAIX. [64Cu]XYIMSR-06 is a new low-molecular-weight PET ligand targeting CAIX, which can image localized and metastatic ccRCC.
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