Development of an imaging-guided CEA-pretargeted radionuclide treatment of advanced colorectal cancer: first clinical results

Br J Cancer. 2013 Aug 20;109(4):934-42. doi: 10.1038/bjc.2013.376. Epub 2013 Jul 16.


Background: Radiolabelled antibody targeting of cancer is limited by slow blood clearance. Pretargeting with a non-radiolabelled bispecific monoclonal antibody (bsMAb) followed by a rapidly clearing radiolabelled hapten peptide improves tumour localisation. The primary goals of this first pretargeting study in patients with the anti-CEACAM5 × anti-hapten (HSG) bsMAb, TF2, and the radiolabelled hapten-peptide, IMP288, were to assess optimal pretargeting conditions and safety in patients with metastatic colorectal cancer (CRC).

Methods: Different dose schedules were studied in four cohorts of five patients: (1) shortening the interval between the bsMAb and peptide administration (5 days vs 1 day), (2) escalating the TF2 dose (from 75 to 150 mg), and (3) reducing the peptide dose (from 100 to 25 μg). After confirmation of tumour targeting by (111)In-IMP288, patients were treated with a bsMAb/(177)Lu-IMP288 cycle.

Results: Rapid and selective tumour targeting of the radiolabelled peptide was visualised within 1 h, with high tumour-to-tissue ratios (>20 at 24 h). Improved tumour targeting was achieved with a 1-day interval between the administration of the bsMAb and the peptide and with the 25-μg peptide dose. High (177)Lu-IMP288 doses (2.5-7.4 GBq) were well tolerated, with some manageable TF2 infusion reactions, and transient grades 3-4 thrombocytopaenia in 10% of the patients who received (177)Lu-IMP288.

Conclusion: This phase I study demonstrates for the first time that pretargeting with bsMAb TF2 and radiolabelled IMP288 in patients with CEA-expressing CRC is feasible and safe. With this pretargeting method, tumours are specifically and rapidly targeted.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antibodies, Bispecific / therapeutic use*
  • Carcinoembryonic Antigen / immunology*
  • Cohort Studies
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / radiotherapy*
  • Female
  • GPI-Linked Proteins / immunology
  • Haptens / immunology*
  • Heterocyclic Compounds, 1-Ring / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Oligopeptides / therapeutic use*
  • Radioimmunotherapy / methods*


  • Antibodies, Bispecific
  • CEACAM5 protein, human
  • Carcinoembryonic Antigen
  • DOTA-tyrosyl-lysyl(histaminyl-succinyl-glycyl)-glutamyl-lysyl(histaminyl-succinyl-glycyl)amide
  • GPI-Linked Proteins
  • Haptens
  • Heterocyclic Compounds, 1-Ring
  • Oligopeptides