体内分布
肾透明细胞癌
癌症研究
Spect成像
放射性核素治疗
化学
药代动力学
体内
显像剂
肾细胞癌
医学
核医学
病理
体外
药理学
生物化学
生物
生物技术
作者
Xing Yang,Il Minn,Steven P. Rowe,Sangeeta Ray Banerjee,Michael A. Gorin,Mary Brummet,Hye Soo Lee,Soo Min Koo,Polina Sysa‐Shah,Ronnie C. Mease,Sridhar Nimmagadda,Mohamad E. Allaf,Martin G. Pomper
出处
期刊:Oncotarget
[Impact Journals, LLC]
日期:2015-09-16
卷期号:6 (32): 33733-33742
被引量:45
标识
DOI:10.18632/oncotarget.5254
摘要
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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