Preclinical radioimmunotargeting of folate receptor alpha using the monoclonal antibody conjugate DOTA-MORAb-003

Nucl Med Biol. 2008 Apr;35(3):343-51. doi: 10.1016/j.nucmedbio.2007.12.008.


Introduction: The in vitro and in vivo behavior of the radiolabeled monoclonal antibody MORAb-003 was investigated as a prelude to a clinical trial.

Methods: The cellular retention of 111In- and 131I-labeled MORAb-003 was investigated using IGROV1 and SW620 cells. Biodistribution studies in tumor-bearing mice were performed with the more favorable agent.

Results: Five 1,4,7,10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid (DOTA) molecules were conjugated to MORAb-003 with no apparent loss of immunoreactivity. Radiolabeled MORAb-003 had a high affinity for the folate receptor alpha (FRA) expressed by both IGROV1 and SW620 cells and was found to bind to around 8 x 10(5) and 7 x 10(5) sites/cell, respectively. Both cancer cell lines were found to internalize both 131I- and 111In-labeled MORAb-003, but 111In was retained and 131I was released as iodide. In athymic mice, 111In-DOTA-MORAb-003 was cleared from the blood with a single exponential biological clearance rate of 110 h. The uptake in SW620 tumors was 32+/-5%ID/g after 4 days. The clearance rate of activity from normal organs such as liver, kidney and spleen was similar to the blood clearance and was 5.36%ID/g, 4.03%ID/g and 4.36%ID/g at 1 day postinjection and 2.14%ID/g, 1.65%ID/g and 3.74%ID/g after 8 days, respectively. In a pilot clinical study, the biodistribution and tumor targeting of 111In-MORAb-003 was assessed in three patients undergoing treatment with cold MORAb-003.

Conclusion: MORAb-003 is an attractive antibody for radioimmunoscintigraphy and possibly radioimmunotherapy of FRA-expressing cancers in addition to its potential direct therapeutic effects.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Biological Transport, Active
  • Carrier Proteins / analysis*
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Drug Evaluation, Preclinical
  • Female
  • Folate Receptors, GPI-Anchored
  • Heterocyclic Compounds, 1-Ring / pharmacokinetics*
  • Humans
  • Immunoconjugates / pharmacokinetics
  • Indium Radioisotopes / pharmacokinetics
  • Iodine Radioisotopes / pharmacokinetics
  • Male
  • Metabolic Clearance Rate
  • Mice
  • Mice, Nude
  • Neoplasm Recurrence, Local / diagnostic imaging
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasms, Glandular and Epithelial / diagnostic imaging
  • Neoplasms, Glandular and Epithelial / drug therapy
  • Ovarian Neoplasms / diagnostic imaging
  • Ovarian Neoplasms / drug therapy
  • Pilot Projects
  • Radiography
  • Radioimmunodetection / methods*
  • Radiopharmaceuticals / pharmacokinetics
  • Receptors, Cell Surface / analysis*
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / metabolism
  • Tissue Distribution


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Carrier Proteins
  • Folate Receptors, GPI-Anchored
  • Heterocyclic Compounds, 1-Ring
  • Immunoconjugates
  • Indium Radioisotopes
  • Iodine Radioisotopes
  • Radiopharmaceuticals
  • Receptors, Cell Surface
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • farletuzumab