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Promising clinical performance of pretargeted immuno-PET with anti-CEA bispecific antibody and gallium-68-labelled IMP-288 peptide for imaging colorectal cancer metastases: a pilot study

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Abstract

Introduction

This pilot study evaluated the imaging performance of pretargeted immunological positron emission tomography (immuno-PET) using an anti-carcinoembryonic antigen (CEA) recombinant bispecific monoclonal antibody (BsMAb), TF2 and the [68Ga]Ga-labelled HSG peptide, IMP288, in patients with metastatic colorectal carcinoma (CRC).

Patients and methods

Patients requiring diagnostic workup of CRC metastases or in case of elevated CEA for surveillance were prospectively studied. They had to present with elevated CEA serum titre or positive CEA tumour staining by immunohistochemistry of a previous biopsy or surgical specimen. All patients underwent endoscopic ultrasound (EUS), chest-abdominal-pelvic computed tomography (CT), abdominal magnetic resonance imaging (MRI) and positron emission tomography using [18F]fluorodeoxyglucose (FDG-PET). For immuno-PET, patients received intravenously 120 nmol of TF2 followed 30 h later by 150 MBq of [68Ga]Ga-labelled IMP288, both I.V. The gold standard was histology and imaging after 6-month follow-up.

Results

Eleven patients were included. No adverse effects were reported after BsMAb and peptide injections. In a per-patient analysis, immuno-PET was positive in 9/11 patients. On a per-lesion analysis, 12 of 14 lesions were positive with immuno-PET. Median SUVmax, MTV and TLG were 7.65 [3.98–13.94, SD 3.37], 8.63 cm3 [1.98–46.64; SD 14.83] and 37.90 cm3 [8.07–127.5; SD 43.47] respectively for immuno-PET lesions. Based on a per-lesion analysis, the sensitivity, specificity, positive-predictive value and negative-predictive value were, respectively, 82%, 25%, 82% and 25% for the combination of EUS/CT/MRI; 76%, 67%, 87% and 33% for FDG-PET; and 88%, 100%, 100% and 67% for immuno-PET. Immuno-PET had an impact on management in 2 patients.

Conclusion

This pilot study showed that pretargeted immuno-PET using anti-CEA/anti-IMP288 BsMAb and a [68Ga]Ga-labelled hapten was safe and feasible, with promising diagnostic performance.

Trial registration

ClinicalTrials.gov NCT02587247

Registered 27 October 2015

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References

  1. Ferlay J, Shin H-R, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917. https://doi.org/10.1002/ijc.25516.

    Article  CAS  PubMed  Google Scholar 

  2. Salaün P-Y, Abgral R, Malard O, et al. Good clinical practice recommendations for the use of PET/CT in oncology. Eur J Nucl Med Mol Imaging. 2020;47:28–50. https://doi.org/10.1007/s00259-019-04553-8.

    Article  PubMed  Google Scholar 

  3. Gauthé M, Richard-Molard M, Cacheux W, et al. Role of fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography in gastrointestinal cancers. Dig Liver Dis Off J Ital Soc Gastroenterol Ital Assoc Study Liver. 2015;47:443–54. https://doi.org/10.1016/j.dld.2015.02.005.

    Article  Google Scholar 

  4. Deleau C, Buecher B, Rousseau C, et al. Clinical impact of fluorodeoxyglucose-positron emission tomography scan/computed tomography in comparison with computed tomography on the detection of colorectal cancer recurrence. Eur J Gastroenterol Hepatol. 2011;23:275–81. https://doi.org/10.1097/MEG.0b013e328343eaa0.

    Article  PubMed  Google Scholar 

  5. Mainenti PP, Mancini M, Mainolfi C, et al. Detection of colo-rectal liver metastases: prospective comparison of contrast enhanced US, multidetector CT, PET/CT, and 1.5 tesla MR with extracellular and reticulo-endothelial cell specific contrast agents. Abdom Imaging. 2010;35:511–21. https://doi.org/10.1007/s00261-009-9555-2.

    Article  PubMed  Google Scholar 

  6. Sahani DV, Kalva SP, Fischman AJ, et al. Detection of liver metastases from adenocarcinoma of the colon and pancreas: comparison of mangafodipir trisodium-enhanced liver MRI and whole-body FDG PET. AJR Am J Roentgenol. 2005;185:239–46. https://doi.org/10.2214/ajr.185.1.01850239.

    Article  PubMed  Google Scholar 

  7. Floriani I, Torri V, Rulli E, et al. Performance of imaging modalities in diagnosis of liver metastases from colorectal cancer: a systematic review and meta-analysis. J Magn Reson Imaging. 2010;31:19–31. https://doi.org/10.1002/jmri.22010.

    Article  PubMed  Google Scholar 

  8. Bailly C, Cléry P-F, Faivre-Chauvet A, et al. Immuno-PET for clinical theranostic approaches. Int J Mol Sci. 2016;18. https://doi.org/10.3390/ijms18010057.

  9. Kraeber-Bodéré F, Rousseau C, Bodet-Milin C, et al. A pretargeting system for tumor PET imaging and radioimmunotherapy. Front Pharmacol. 2015;6:54. https://doi.org/10.3389/fphar.2015.00054.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Vrabie CD, Ceauşu M, Petrescu A, et al. The usefulness of immunohistochemistry in sporadic colorectal cancer. Romanian J Morphol Embryol Rev Roum Morphol Embryol. 2008;49:525–35.

    Google Scholar 

  11. Benchimol S, Fuks A, Jothy S, et al. Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule. Cell. 1989;57:327–34. https://doi.org/10.1016/0092-8674(89)90970-7.

    Article  CAS  PubMed  Google Scholar 

  12. Rossi EA, Goldenberg DM, Cardillo TM, et al. Stably tethered multifunctional structures of defined composition made by the dock and lock method for use in cancer targeting. Proc Natl Acad Sci U S A. 2006;103:6841–6. https://doi.org/10.1073/pnas.0600982103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bodet-Milin C, Faivre-Chauvet A, Carlier T, et al. Immuno-PET using anticarcinoembryonic antigen bispecific antibody and 68Ga-labeled peptide in metastatic medullary thyroid carcinoma: clinical optimization of the Pretargeting parameters in a first-in-human trial. J Nucl Med. 2016;57:1505–11. https://doi.org/10.2967/jnumed.116.172221.

    Article  CAS  PubMed  Google Scholar 

  14. Rousseau C, Goldenberg DM, Colombie M, et al. Initial clinical results of a novel immuno-PET theranostic probe in HER2-negative breast cancer. J Nucl Med. 2020;jnumed.119.236000.

  15. Foubert F, Gouard S, Saï-Maurel C, et al. Sensitivity of pretargeted immunoPET using 68Ga-peptide to detect colonic carcinoma liver metastases in a murine xenograft model: comparison with 18FDG PET-CT. Oncotarget. 2018;9:27502–13. https://doi.org/10.18632/oncotarget.25514.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Karacay H, Sharkey RM, McBride WJ, et al. Optimization of hapten-peptide labeling for pretargeted immunoPET of bispecific antibody using generator-produced 68Ga. J Nucl Med. 2011;52:555–9. https://doi.org/10.2967/jnumed.110.083568.

    Article  CAS  PubMed  Google Scholar 

  17. Laessig D, Nagel D, Heinemann V, et al. Importance of CEA and CA 15-3 during disease progression in metastatic breast cancer patients. Anticancer Res. 2007;27:1963–8.

    CAS  PubMed  Google Scholar 

  18. Andersson M, Johansson L, Minarik D, et al. Effective dose to adult patients from 338 radiopharmaceuticals estimated using ICRP biokinetic data, ICRP/ICRU computational reference phantoms and ICRP 2007 tissue weighting factors. EJNMMI Phys. 2014;1:9. https://doi.org/10.1186/2197-7364-1-9.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Bodet-Milin C, Ferrer L, Rauscher A, et al. Pharmacokinetics and dosimetry studies for optimization of pretargeted radioimmunotherapy in CEA-expressing advanced lung cancer patients. Front Med. 2015;2:84. https://doi.org/10.3389/fmed.2015.00084.

    Article  Google Scholar 

  20. Bardia A, Mayer IA, Vahdat LT, et al. Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer. N Engl J Med. 2019;380:741–51. https://doi.org/10.1056/NEJMoa1814213.

    Article  CAS  PubMed  Google Scholar 

  21. Schoffelen R, Boerman OC, Goldenberg DM, et al. Development of an imaging-guided CEA-pretargeted radionuclide treatment of advanced colorectal cancer: first clinical results. Br J Cancer. 2013;109:934–42. https://doi.org/10.1038/bjc.2013.376.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported in part by grants from the University Hospital of Nantes, the French National Agency for Research, called “Investissements d’Avenir” IRON Labex ANR-11-LABX-0018-01 and ArronaxPlus Equipex ANR-11-EQPX-0004 and the INCa-DGOS-Inserm_12558 (SIRIC ILIAD).

Author information

Authors and Affiliations

  1. Université de Nantes, CHU Nantes, CNRS, Inserm, CRCINA, F-44000, Nantes, France

    Y. Touchefeu, C. Bailly, T. Eugène, M. Bourgeois, A. Faivre-Chauvet, T. Carlier, F. Kraeber-Bodere & C. Bodet-Milin

  2. Institut des Maladies de l’Appareil Digestif, University Hospital, Nantes, France

    Y. Touchefeu

  3. Radiology department, University Hospital, Nantes, France

    E. Frampas & A. David

  4. Université de Nantes, ICO Gauducheau, CNRS, Inserm, CRCINA, F-44000, Nantes, France

    C. Rousseau

  5. Pathology Department, University Hospital, Nantes, France

    C. Bossard

  6. Pharmacy Unit, ICO Cancer Center, Saint-Herblain, France

    A. Rauscher

  7. Biology Department, University Hospital, Nantes, France

    D. Masson

  8. Délégation à la Recherche Clinique et à l’Innovation, University Hospital, Nantes, France

    E. Cerato

  9. Immunomedics, Inc., Morris Plains, NJ, USA

    R. M. Sharkey & D. M. Goldenberg

  10. IBC Pharmaceuticals, Inc., Morris Plains, NJ, USA

    D. M. Goldenberg

  11. GIP Arronax, F-44800, Saint-Herblain, France

    J. Barbet

  12. Université de Nantes, CHU Nantes, ICO Gauducheau, CNRS, Inserm, CRCINA, F-44000, Nantes, France

    F. Kraeber-Bodere

Authors
  1. Y. Touchefeu
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  2. C. Bailly
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  3. E. Frampas
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  4. T. Eugène
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  5. C. Rousseau
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  6. M. Bourgeois
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  8. A. Faivre-Chauvet
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  15. D. M. Goldenberg
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  17. F. Kraeber-Bodere
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  18. C. Bodet-Milin
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Corresponding author

Correspondence to Y. Touchefeu.

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Conflict of interest

Dr. Goldenberg was Chairman of the Board and Chief Scientific Officer of Immunomedics, Inc., a publicly traded company, at the time this research was conducted, and was also a stockholder in the company. Immunomedics contributed materials to the study. Dr. Goldenberg is a patent inventor and is eligible to receive royalties from Immunomedics. Dr. Goldenberg was Chairman of the Board of IBC Pharmaceuticals, Inc., at the time this research was conducted. IBC Pharmaceuticals contributed materials to the study. Dr. Sharkey was an employee of Immunomedics during this study and also held stock options. Other authors have no conflict of interest to disclose.

Ethics approval

The trial sponsored by the Nantes University Hospital was approved by the responsible ethics committee (CPP) and registered at ClinicalTrials.gov (NCT02587247). All patients signed informed consent.

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This article is part of the Topical Collection on Oncology - Digestive tract.

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Touchefeu, Y., Bailly, C., Frampas, E. et al. Promising clinical performance of pretargeted immuno-PET with anti-CEA bispecific antibody and gallium-68-labelled IMP-288 peptide for imaging colorectal cancer metastases: a pilot study. Eur J Nucl Med Mol Imaging 48, 874–882 (2021). https://doi.org/10.1007/s00259-020-04989-3

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