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High-quality 124I-labelled monoclonal antibodies for use as PET scouting agents prior to 131I-radioimmunotherapy

  • Iris Verel
  • Gerard W. M. Visser
  • Maria J. W. D. Vosjan
  • Ronald Finn
  • Ronald Boellaard
  • Guus A. M. S. van DongenEmail author
Original Article

Abstract

Purpose

Monoclonal antibodies (MAbs) labelled with 124I are an attractive option for quantitative imaging with positron emission tomography (PET) in a scouting procedure prior to 131I-radioimmunotherapy (131I-RIT). In this study, three important items in the labelling of MAbs with 124I were introduced to obtain optimal and reproducible product quality: restoration of radiation-induced inorganic deterioration of the starting 124I solution, radiation protection during and after 124I labelling, and synchronisation of the I/MAb molar ratio.

Methods

A new method was applied, using an NaIO3/NaI carrier mix, realising in one step >90% restoration of deteriorated 124I into the iodide form and chemical control over the I/MAb molar ratio. Chimeric MAb (cMAb) U36 and the murine MAbs 425 and E48 were labelled with 124I using the so-called Iodogen-coated MAb method, as this method provides optimal quality conjugates under challenging radiation conditions. As a standardising condition, NaIO3/NaI carrier mix was added at a stoichiometric I/MAb molar ratio of 0.9. For comparison, MAbs were labelled with 131I and with a mixture of 124I, 123I, 126I and 130I.

Results

Labelling with 124I in this setting resulted in overall yields of >70%, a radiochemical purity of >95%, and preservation of MAb integrity and immunoreactivity, including at the patient dose level (85 MBq). No significant quality differences were observed when compared with 131I products, while the iodine isotope mixture gave exactly the same labelling efficiency for each of the isotopes, excluding a different chemical reactivity of 124I-iodide. The scouting performance of 124I-cMAb U36 labelled at the patient dose level was evaluated in biodistribution studies upon co-injection with 131I-labelled cMAb U36, and by PET imaging in nude mice bearing the head and neck cancer xenograft line HNX-OE. 124I-cMAb and 131I-cMAb U36 labelled with a synchronised I/MAb molar ratio gave fully concordant tissue uptake values. Selective tumour uptake was confirmed with immuno-PET, revealing visualisation of 15 out of 15 tumours.

Conclusion

These results pave the way for renewed evaluation of the potential of 124I-immuno-PET for clinical applications.

Keywords

Iodine-124 Iodine-131 124I regeneration Monoclonal antibody labelling Positron emission tomography 

Notes

Acknowledgements

The authors thank Anton H. Braker (BV Cyclotron, VU University) for performing radioiodine regeneration using the Pt/H2 column, Fred L. Buijs (Radionuclide Center, VU University Medical Center) for the PET analyses, Marijke Stigter (Otolaryngology/Head and Neck Surgery, VU University Medical Center) for assistance in the animal experiments and Peter J. van Leuffen and Roel Mooy of BV Cyclotron (VU University) for supplying test mixtures of radioiodine isotopes. Supported by grants form the European Union FP6, LSHC-CT-2003-5032, STROMA; this publication reflects only the authors’ view. The European Commission is not liable for any use that may be made of the information contained.

References

  1. 1.
    Matsku S, Kirchgebner H, Nissen M. Iodination of monoclonal IgG antibodies at a sub-stoichiometric level: immunoreactivity changes related to the site of iodine incorporation. Nucl Med Biol 1987;14:451–7Google Scholar
  2. 2.
    Nikula TK, Bocchia M, Curcio MJ, Sgouros G, Ma Y, Finn RD, Scheinberg DA. Impact of the high tyrosine fraction in complementarity determining regions: measured and predicted effects of radioiodination on IgG immunoreactivity. Mol Immunol 1995;32:865–72CrossRefPubMedGoogle Scholar
  3. 3.
    Wilson CB, Snook DE, Dhokia B, et al. Quantitative measurement of monoclonal antibody distribution and blood flow using positron emission tomography and 124Iodine in patients with breast cancer. Int J Cancer 1991;47:344–7PubMedGoogle Scholar
  4. 4.
    Larson SM, Pentlow KS, Volkow ND, et al. PET scanning of iodine-124-3F8 as an approach to tumor dosimetry during treatment planning for radioimmunotherapy in a child with neuroblastoma. J Nucl Med 1992;33:2020–3PubMedGoogle Scholar
  5. 5.
    Daghighian F, Pentlow KS, Larson SM, et al. Development of a method to measure kinetics of radiolabelled monoclonal antibody in human tumour with applications to microdosimetry: positron emission tomography studies of iodine-124 labelled 3F8 monoclonal antibody in glioma. Eur J Nucl Med 1993;20:402–9PubMedGoogle Scholar
  6. 6.
    Visser GWM. Inorganic astatine chemistry. Part II. The chameleon behaviour and electrophilicity of At-species. Radiochim Acta 1989;47:97–103Google Scholar
  7. 7.
    Visser GWM, Klok RP, Klein Gebbinck JW, ter Linden T, van Dongen GAMS, Molthoff CF. Optimal quality 131I-monoclonal antibodies on high-dose labeling in a large reaction volume and temporarily coating the antibody with IODO-GEN. J Nucl Med 2001;42:509–19PubMedGoogle Scholar
  8. 8.
    Vrouenraets MB, Visser GWM, Stigter M, Oppelaar H, Snow GB, van Dongen GAMS. Targeting of aluminum (III) phthalocyanine tetrasulfonate by use of internalizing monoclonal antibodies: improved efficacy in photodynamic therapy. Cancer Res 2001;61:1970–5PubMedGoogle Scholar
  9. 9.
    Braker AH, Moet FP, van der Zwart RE, Eersels JLH, Herscheid JDM. Adsorption of radioiodine on platinum: a fast and simple column method to obtain concentrated and pure radioiodide in either water or anhydrous solvents. Appl Radiat Isot 2002;57:475–82CrossRefPubMedGoogle Scholar
  10. 10.
    Visser GWM, Gerretsen M, Herscheid JDM, Snow GB, van Dongen GAMS. Labeling of monoclonal antibodies with 186Re using the MAG3 chelate for radioimmunotherapy of cancer: a technical protocol. J Nucl Med 1993;34:1953–63PubMedGoogle Scholar
  11. 11.
    Chakrabarti MC, Le N, Paik CH, De Graff WG, Carrasquillo JA. Prevention of radiolysis of monoclonal antibody during labeling. J Nucl Med 1996;37:1384–8PubMedGoogle Scholar
  12. 12.
    Jayson GC, Zweit J, Jackson A, et al. Molecular imaging and biological evaluation of HuMV833 anti-VEGF antibody: implications for trial design of antiangiogenic antibodies. J Natl Cancer Inst 2002;94:1484–93CrossRefPubMedGoogle Scholar
  13. 13.
    Lindmo T, Boven E, Luttita F, Fedorko J, Bunn Jr PA. Determination of the immunoreactive fraction of radiolabeled monoclonal antibodies by linear extrapolation to binding at infinite antigen excess. J Immunol Methods 1984;72:77–89CrossRefPubMedGoogle Scholar
  14. 14.
    Guide for the care and use of laboratory animals. NIH publication 86-23. Government Printing Office, Washington; 1985Google Scholar
  15. 15.
    Boellaard R, Buijs F, de Jong HWAM, Lenox M, Gremillion T, Lammertsma AA. Characterization of a single LSO crystal layer high resolution research tomograph. Phys Med Biol 2003;48:429–48CrossRefPubMedGoogle Scholar
  16. 16.
    Verel I, Visser GWM, Boellaard R, et al. Quantitative zirconium-89 immuno-PET for in vivo scouting of yttrium-90-labeled monoclonal antibodies in xenograft-bearing nude mice. J Nucl Med 2003;44:1663–70PubMedGoogle Scholar
  17. 17.
    Pentlow KS, Graham MC. Quantitative imaging of I-124 using positron emission tomography with applications to radioimmunodiagnosis and radioimmunotherapy. Med Phys 1991;18:357–66CrossRefPubMedGoogle Scholar
  18. 18.
    Westera G, Reist HW, Buchegger F, et al. Radioimmuno positron emission tomography with monoclonal antibodies: a new approach to quantifying in vivo tumour concentration and biodistribution for radioimmunotherapy. Nucl Med Commun 1991;12:429–37PubMedGoogle Scholar
  19. 19.
    Bakir MA, Eccles SA, Babich JW, et al. c-erbB2 Protein overexpression in breast cancer as a target for PET using iodine-124-labeled monoclonal antibodies. J Nucl Med 1992;33:2154–60PubMedGoogle Scholar
  20. 20.
    Rubin SC, Kairemo KJA, Brownell A-L, et al. High-resolution positron emission tomography of human ovarian cancer in nude rats using 124I-labeled monoclonal antibodies. Gynecol Oncol 1993;48:61–7CrossRefPubMedGoogle Scholar
  21. 21.
    Kairemo KJA. Positron emission tomography of monoclonal antibodies. Acta Oncol 1993;32:825–30PubMedGoogle Scholar
  22. 22.
    Sundaresan G, Yazaki PJ, Shively JE, Finn RD, Larson SM, Raubitschek AA, Williams LE, Chatziioannou AF, Gambhir SS, Wu AA. 124I-Labeled engineered anti-CEA minibodies and diabodies allow high-contrast, antigen specific small-animal PET imaging of xenografts in athymic mice. J Nucl Med 2003;44:1962–9PubMedGoogle Scholar
  23. 23.
    Finn R, Cheung N-KV, Divgi C, et al. Technical challenges associated with the radiolabeling of monoclonal antibodies utilizing short-lived, positron emitting radionuclides. Nucl Med Biol 1991;18:9–13CrossRefGoogle Scholar
  24. 24.
    Lee FT, Hall C, Rigopoulos A, et al. Immuno-PET of human colon xenograft-bearing BALB/c nude mice using 124I-CDR-grafted humanized A33 monoclonal antibody. J Nucl Med 2001;42:764–9PubMedGoogle Scholar
  25. 25.
    Collingridge DR, Carroll VA, Glaser M, et al. The development of [124I]iodinated-VG76e: a novel tracer for imaging vascular endothelial growth factor in vivo using positron emission tomography. Cancer Res 2002;62:5912–9PubMedGoogle Scholar
  26. 26.
    Glaser M, Collingridge DR, Aboagye EO, et al. Iodine-124 labelled annexin-V as a potential radiotracer to study apoptosis using positron emission tomography. Appl Radiat Isot 2003;58:55–62CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Iris Verel
    • 1
    • 2
  • Gerard W. M. Visser
    • 3
  • Maria J. W. D. Vosjan
    • 1
  • Ronald Finn
    • 4
  • Ronald Boellaard
    • 5
  • Guus A. M. S. van Dongen
    • 1
    Email author
  1. 1.Department of Otolaryngology/Head and Neck SurgeryVU University Medical CenterAmsterdamThe Netherlands
  2. 2.Center for Molecular Imaging ResearchMassachusetts General HospitalCharlestownUSA
  3. 3.Radionuclide CenterVU University Medical CenterAmsterdamThe Netherlands
  4. 4.Memorial Sloan-Kettering Cancer CenterNew YorkUSA
  5. 5.PET CenterVU University Medical CenterAmsterdamThe Netherlands

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