Imaging of carbonic anhydrase IX with an 111In-labeled dual-motif inhibitor
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Xing Yang1,*, Il Minn1,*, Steven P. Rowe1, Sangeeta Ray Banerjee1, Michael A. Gorin2, Mary Brummet1, Hye Soo Lee1, Soo Min Koo1, Polina Sysa-Shah1, Ronnie C. Mease1, Sridhar Nimmagadda1, Mohamad E. Allaf2, Martin G. Pomper1
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
*These authors have contributed equally to this work
Martin G. Pomper, e-mail: [email protected]
Xing Yang, e-mail: [email protected]
Keywords: CAIX, single photon emission computed tomography, molecular imaging, renal cell carcinoma, indium-111
Received: May 31, 2015 Accepted: September 03, 2015 Published: September 16, 2015
We developed a new scaffold for radionuclide-based imaging and therapy of clear cell renal cell carcinoma (ccRCC) targeting carbonic anhydrase IX (CAIX). Compound XYIMSR-01, a DOTA-conjugated, bivalent, low-molecular-weight ligand, has two moieties that target two separate sites on CAIX, imparting high affinity. We synthesized [111In]XYIMSR-01 in 73.8–75.8% (n = 3) yield with specific radioactivities ranging from 118 – 1,021 GBq/μmol (3,200–27,600 Ci/mmol). Single photon emission computed tomography of [111In]XYIMSR-01 in immunocompromised mice bearing CAIX-expressing SK-RC-52 tumors revealed radiotracer uptake in tumor as early as 1 h post-injection. Biodistribution studies demonstrated 26% injected dose per gram of radioactivity within tumor at 1 h. Tumor-to-blood, muscle and kidney ratios were 178.1 ± 145.4, 68.4 ± 29.0 and 1.7 ± 1.2, respectively, at 24 h post-injection. Retention of radioactivity was exclusively observed in tumors by 48 h, the latest time point evaluated. The dual targeting strategy to engage CAIX enabled specific detection of ccRCC in this xenograft model, with pharmacokinetics surpassing those of previously described radionuclide-based probes against CAIX.
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