Antitenascin antibody 81C6 armed with 177Lu: in vivo comparison of macrocyclic and acyclic ligands

Nucl Med Biol. 2007 Feb;34(2):173-83. doi: 10.1016/j.nucmedbio.2006.11.003. Epub 2007 Jan 17.


Introduction: When labeled with iodine-131, the antitenascin monoclonal antibody (mAb) 81C6 has shown promise as a targeted radiotherapeutic in patients with brain tumors. Because of its more favorable gamma-ray properties, lutetium-177 might be a better low-energy beta-emitter for this type of therapy.

Materials and methods: Chimeric 81C6 (ch81C6) was labeled with (177)Lu using the acyclic 1B4M ligand and the macrocyclic ligands NHS-DOTA and MeO-DOTA and evaluated for binding to tenascin. Three paired-label tissue distribution experiments were performed in normal mice receiving one of the (177)Lu-labeled immunoconjugates plus (125)I-labeled ch81C6 labeled using Iodogen. Paired-label experiments in athymic mice bearing subcutaneous D54 MG human glioma xenografts were done to directly compare the biodistribution of ch81C6-1B4M-(177)Lu and (125)I-labeled ch81C6, and ch81C6-MeO-DOTA-(177)Lu and (125)I-labeled ch81C6. Similar comparisons were done using murine (mu) instead of ch81C6. The primary parameter utilized for evaluation was the (177)Lu/(125)I uptake ratio in each tissue.

Results: In the studies performed in normal mice, the NHS-DOTA ligand yielded the highest (177)Lu/(125)I uptake ratios in tissues indicative of loss of label from the chelate; for this reason, only 1B4M and MeO-DOTA were evaluated further. The (177)Lu/(125)I ratio in bone increased gradually with time for the chimeric conjugates; however, there were no significant differences between ch81C6-1B4M-DTPA-(177)Lu and ch81C6-MeO-DOTA-(177)Lu. In contrast, mu81C6-1B4M-DTPA-(177)Lu and mu81C6-MeO-DOTA-(177)Lu showed a more dramatic increase in the (177)Lu/(125)I ratio in bone - from 2.4+/-0.3 and 1.7+/-0.2 at Day 1 to 8.5+/-1.1 and 4.2+/-0.5 at Day 7, respectively.

Conclusion: With these antitenascin constructs, the nature of the mAb had a profound influence on the relative degree of loss of (177)Lu from these immunoconjugates. MeO-DOTA shows promise as a bifunctional chelate for labeling 81C6 mAbs with (177)Lu.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacokinetics*
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / metabolism*
  • Cell Line, Tumor
  • Glioma / diagnostic imaging
  • Glioma / metabolism*
  • Hydrocarbons, Acyclic / pharmacokinetics
  • Lutetium / pharmacokinetics*
  • Macrocyclic Compounds / pharmacokinetics
  • Metabolic Clearance Rate
  • Mice
  • Mice, Inbred BALB C
  • Organ Specificity
  • Radioisotopes / pharmacokinetics*
  • Radionuclide Imaging
  • Radiopharmaceuticals / pharmacokinetics
  • Tenascin / immunology*
  • Tissue Distribution


  • Antibodies, Monoclonal
  • Hydrocarbons, Acyclic
  • Macrocyclic Compounds
  • Radioisotopes
  • Radiopharmaceuticals
  • Tenascin
  • Lutetium