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

Bioconjug Chem. Mar-Apr 2006;17(2):485-92. doi: 10.1021/bc0502356.


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 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 uptake decreased 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 and other carcinomas.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Neoplasm* / chemistry
  • Antibodies, Neoplasm* / metabolism
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / metabolism
  • Chelating Agents / chemistry
  • Chelating Agents / metabolism
  • Heterocyclic Compounds, 1-Ring* / chemistry
  • Heterocyclic Compounds, 1-Ring* / metabolism
  • Holmium / chemistry
  • Humans
  • Lanthanoid Series Elements / chemistry*
  • Lutetium / chemistry
  • Mice
  • Mice, Nude
  • Molecular Structure
  • Neoplasms* / immunology
  • Neoplasms* / radiotherapy
  • Promethium / chemistry
  • Radioisotopes* / chemistry
  • Radioisotopes* / metabolism
  • Tissue Distribution


  • Antibodies, Neoplasm
  • Antineoplastic Agents
  • B72.3 antibody
  • Chelating Agents
  • Heterocyclic Compounds, 1-Ring
  • Lanthanoid Series Elements
  • Radioisotopes
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • Lutetium
  • Holmium
  • Promethium