High-quality 124I-labelled monoclonal antibodies for use as PET scouting agents prior to 131I-radioimmunotherapy
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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.
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.
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.
These results pave the way for renewed evaluation of the potential of 124I-immuno-PET for clinical applications.
KeywordsIodine-124 Iodine-131 124I regeneration Monoclonal antibody labelling Positron emission tomography
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.
- 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
- 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.Visser GWM. Inorganic astatine chemistry. Part II. The chameleon behaviour and electrophilicity of At-species. Radiochim Acta 1989;47:97–103Google Scholar
- 14.Guide for the care and use of laboratory animals. NIH publication 86-23. Government Printing Office, Washington; 1985Google Scholar
- 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