Radiolanthanide-labeled monoclonal antibody CC49 for radioimmunotherapy of cancer: biological comparison of DOTA conjugates and 149Pm, 166Ho, and 177Lu

Bioconjugate Chemistry
Huma MohsinMichael R Lewis

Abstract

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 conjugated to the anti-TAG-72 monoclonal antibody CC49 for radiolabeling with 149Pm, 166Ho, and 177Lu. While both DOTA conjugates 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 carcinoma xenografts demonstrated that MeO-DOTA afforded higher tumor uptake and lower kidney retention of 177Lu than DOTA-OSSu. The in vitro stability of 149Pm-, 166Ho-, and 177Lu-MeO-DOTA-CC49 was evaluated using serum and hydroxyapatite assays. Serum stability of radiolanthanide-labeled MeO-DOTA-CC49 followed a trend based on the coordination energies of the radiometals, with 177Lu showing the highest stability after 96 to 168 h at 37 C. In contrast, MeO-DOTA-CC49 labeled with all three radiolanthanides was >92% stable to hydroxyapatite challenge for 168 h at 37 C. Comprehensive biodistributions of 149Pm-, 166Ho-, and 177Lu-MeO-DOTA-CC49 were obtained in LS174T-bearing nude mice. Maximum tumor uptake...Continue Reading

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Citations

Mar 22, 2012·Pathology Oncology Research : POR·Yang ZhangYang-de Zhang
Jul 3, 2007·Bioconjugate Chemistry·Fujie TanakaCarlos F Barbas
May 5, 2011·Dalton Transactions : an International Journal of Inorganic Chemistry·Sibaprasad Bhattacharyya, Manish Dixit
Feb 20, 2007·Nuclear Medicine and Biology·Alexander T YordanovMichael R Zalutsky
Jun 27, 2007·Dalton Transactions : an International Journal of Inorganic Chemistry·Rita DelgadoDavid W Price
Oct 30, 2019·EJNMMI Radiopharmacy and Chemistry·Nienke J M KlaassenJ Frank W Nijsen
Mar 11, 2021·Inorganic Chemistry·Lixiong DaiGa-Lai Law
Oct 5, 2013·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Raffaella RossinMarc S Robillard

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