Predictive patient-specific dosimetry and individualized dosing of pretargeted radioimmunotherapy in patients with advanced colorectal cancer

Eur J Nucl Med Mol Imaging. 2014 Aug;41(8):1593-602. doi: 10.1007/s00259-014-2742-6. Epub 2014 Mar 19.


Purpose: Pretargeted radioimmunotherapy (PRIT) with bispecific antibodies (bsMAb) and a radiolabeled peptide reduces the radiation dose to normal tissues. Here we report the accuracy of an (111)In-labeled pretherapy test dose for personalized dosing of (177)Lu-labeled IMP288 following pretargeting with the anti-CEA × anti-hapten bsMAb, TF2, in patients with metastatic colorectal cancer (CRC).

Methods: In 20 patients bone marrow absorbed doses (BMD) and doses to the kidneys were predicted based on blood samples and scintigrams acquired after (111)In-IMP288 injection for individualized dosing of PRIT with (177)Lu-IMP288. Different dose schedules were studied, varying the interval between the bsMAb and peptide administration (5 days vs. 1 day), increasing the bsMAb dose (75 mg vs. 150 mg), and lowering the peptide dose (100 μg vs. 25 μg).

Results: TF2 and (111)In/(177)Lu-IMP288 clearance was highly variable. A strong correlation was observed between peptide residence times and individual TF2 blood concentrations at the time of peptide injection (Spearman's ρ = 0.94, P < 0.0001). PRIT with 7.4 GBq (177)Lu-IMP288 resulted in low radiation doses to normal tissues (BMD <0.5 Gy, kidney dose <3 Gy). Predicted (177)Lu-IMP288 BMD were in good agreement with the actual measured doses (mean ± SD difference -0.0026 ± 0.028 mGy/MBq). Hematological toxicity was mild in most patients, with only two (10 %) having grade 3-4 thrombocytopenia. A correlation was found between platelet toxicity and BMD (Spearman's ρ = 0.58, P = 0.008). No nonhematological toxicity was observed.

Conclusion: These results show that individual high activity doses in PRIT in patients with CEA-expressing CRC could be safely administered by predicting the radiation dose to red marrow and kidneys, based on dosimetric analysis of a test dose of TF2 and (111)In-IMP288.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antibodies, Bispecific / administration & dosage
  • Antibodies, Bispecific / pharmacokinetics
  • Antibodies, Bispecific / therapeutic use
  • Carcinoembryonic Antigen / immunology
  • Colorectal Neoplasms / diagnostic imaging
  • Colorectal Neoplasms / radiotherapy*
  • Female
  • Haptens / immunology
  • Heterocyclic Compounds, 1-Ring / administration & dosage
  • Heterocyclic Compounds, 1-Ring / pharmacokinetics
  • Heterocyclic Compounds, 1-Ring / therapeutic use
  • Humans
  • Indium Radioisotopes / administration & dosage
  • Indium Radioisotopes / pharmacokinetics
  • Indium Radioisotopes / therapeutic use
  • Lutetium / administration & dosage
  • Lutetium / pharmacokinetics
  • Lutetium / therapeutic use
  • Male
  • Middle Aged
  • Oligopeptides / administration & dosage
  • Oligopeptides / pharmacokinetics
  • Oligopeptides / therapeutic use
  • Precision Medicine / methods*
  • Radiation Dosage*
  • Radioimmunotherapy*
  • Radiometry / methods*
  • Tomography, Emission-Computed, Single-Photon


  • Antibodies, Bispecific
  • Carcinoembryonic Antigen
  • DOTA-tyrosyl-lysyl(histaminyl-succinyl-glycyl)-glutamyl-lysyl(histaminyl-succinyl-glycyl)amide
  • Haptens
  • Heterocyclic Compounds, 1-Ring
  • Indium Radioisotopes
  • Oligopeptides
  • Lutetium