Radiolanthanide-Labeled Monoclonal Antibody CC49 for Radioimmunotherapy of Cancer: Biological Comparison of DOTA Conjugates and 149Pm, 166Ho, and 177Lu

详细信息    查看全文

• 作者：Huma Mohsin ; Fang Jia ; Geethapriya Sivaguru ; Michael J. Hudson ; Tiffani D. Shelton ; Timothy J. Hoffman ; Cathy S. Cutler ; Alan R. Ketring ; Phillip S. Athey ; Jaime Simó ; n ; R. Keith Frank ; Silvia S
• 刊名：Bioconjugate Chemistry
• 出版年：2006
• 出版时间：March 2006
• 年：2006
• 卷：17
• 期：2
• 页码：485 - 492
• 全文大小：110K
• 年卷期：v.17,no.2(March 2006)
• ISSN：1520-4812

文摘

The radiolanthanides ¹⁴⁹Pm, ¹⁶⁶Ho, and ¹⁷⁷Lu have decay characteristics suitable for radioimmunotherapy (RIT)of cancer. N-Hydroxysulfosuccinimidyl DOTA (DOTA-OSSu) and methoxy-DOTA (MeO-DOTA) were conjugatedto the anti-TAG-72 monoclonal antibody CC49 for radiolabeling with ¹⁴⁹Pm, ¹⁶⁶Ho, and ¹⁷⁷Lu. While both DOTAconjugates could be labeled to high specific activity with ¹⁷⁷Lu, MeO-DOTA afforded superior conjugate stability,radiolabeling, and radiochemical purity. Pilot biodistributions in nude mice bearing LS174T human colon carcinomaxenografts demonstrated that MeO-DOTA afforded higher tumor uptake and lower kidney retention of ¹⁷⁷Lu thanDOTA-OSSu. The in vitro stability of ¹⁴⁹Pm-, ¹⁶⁶Ho-, and ¹⁷⁷Lu-MeO-DOTA-CC49 was evaluated using serumand hydroxyapatite assays. Serum stability of radiolanthanide-labeled MeO-DOTA-CC49 followed a trend basedon the coordination energies of the radiometals, with ¹⁷⁷Lu showing the highest stability after 96 to 168 h at 37s/entities/deg.gif">C. In contrast, MeO-DOTA-CC49 labeled with all three radiolanthanides was >92% stable to hydroxyapatitechallenge for 168 h at 37 s/entities/deg.gif">C. Comprehensive biodistributions of ¹⁴⁹Pm-, ¹⁶⁶Ho-, and ¹⁷⁷Lu-MeO-DOTA-CC49were obtained in LS174T-bearing nude mice. Maximum tumor uptakes were 100.0% ID/g for ¹⁴⁹Pm at 96 h,69.5% ID/g for ¹⁶⁶Ho at 96 h, and 132.4% ID/g for ¹⁷⁷Lu at 168 h. Normal organ uptakes were generally low,except in the liver, spleen, and kidney at early time points. By 96 to 168 h postinjection, nontarget organ uptakedecreased to approximately 7% ID/g (kidney), 12% ID/g (spleen), and 20% ID/g (liver) for each radiolanthanide.When labeled with ¹⁴⁹Pm, ¹⁶⁶Ho, and ¹⁷⁷Lu, MeO-DOTA-CC49 has potential for RIT of colorectal cancer andother carcinomas.