期刊
ONCOTARGET
卷 6, 期 32, 页码 33733-33742出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.5254
关键词
CAIX; single photon emission computed tomography; molecular imaging; renal cell carcinoma; indium-111
资金
- [CA134675]
- [CA197470]
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 [In-111]XYIMSR-01 in 73.8-75.8% (n = 3) yield with specific radioactivities ranging from 118 -1,021 GBq/mu mol (3,200-27,600 Ci/mmol). Single photon emission computed tomography of [In-111]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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