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

Abstract

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.

• Authors: Rafke Schoffelen, Wietske Woliner-van der Weg, Eric P Visser, David M Goldenberg, Robert M Sharkey, William J McBride, Chien-Hsing Chang, Edmund A Rossi, Winette T A van der Graaf, Wim J G Oyen, Otto C Boerman
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 41 Issue 8 Pg. 1593-602 (Aug 2014) ISSN: 1619-7089 [Electronic] Germany
• PMID: 24643780 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• 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

Topics

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