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European Journal of Nuclear Medicine and Molecular Imaging

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01-12-2004 | Original Article

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

Authors: Iris Verel, Gerard W. M. Visser, Maria J. W. D. Vosjan, Ronald Finn, Ronald Boellaard, Guus A. M. S. van Dongen

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 12/2004

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.

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Title: High-quality 124I-labelled monoclonal antibodies for use as PET scouting agents prior to 131I-radioimmunotherapy
Authors: Iris Verel
Gerard W. M. Visser
Maria J. W. D. Vosjan
Ronald Finn
Ronald Boellaard
Guus A. M. S. van Dongen
Publication date: 01-12-2004
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 12/2004
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-004-1632-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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