PET/MRI with 89Zr-labelled antibodies provides insights into altered antibody pharmacokinetics in the chick embryo model

Résumé fourni par la source

The fertilised chicken egg ( in ovo ) is a promising, ethically acceptable intermediate model for preselection of radiotracers prior to testing in rodents. The behaviour of monoclonal antibodies in ovo for application in positron emission tomography is yet to be explored. Here, we investigated the potential of this model for development of radiolabelled antibodies using simultaneous PET and magnetic resonance imaging. The biodistribution of the model antibody [ 89 Zr]Zr-nSuc-Df-Denosumab was assessed at different time points and specific activities. The study was complemented with the more established [ 89 Zr]Zr-nSuc-Df-Atezolizumab. Both 89 Zr-labelled antibodies were synthesised with radiochemical yields >70 %, radiochemical purities >98 % and immune reactive fractions greater than 99 %. [ 89 Zr]Zr-nSuc-Df-Denosumab showed initial uptake in the chick embryonic heart, spleen and liver, while brain accumulation was negligible at all investigated time points. Using radiotracer in lower specific activities appeared to slow down biodistribution and clearance. By 23 h p.i. , most activity was localised in the gallbladder, suggesting hepatobiliary excretion. A comparable biodistribution profile was observed for [ 89 Zr]Zr-nSuc-Df-Atezolizumab at 19 h p.i. The rapid clearance of both IgG antibodies is likely caused by the absence of neonatal Fc receptors (FcRn) in birds, which in mammals mediate IgG recycling and thereby prolong antibody half-life. In conclusion, while the overall biodistribution patterns were broadly comparable to those reported in mammals, this first exploratory investigation of 89 Zr-labelled antibodies in ovo revealed markedly altered pharmacokinetics in chick embryos, most likely due to the absence of FcRn. These findings indicate predominantly non-specific distribution and clearance of these radiolabelled antibodies in fertilised chicken eggs. This study underscores the importance of considering species-specific differences when interpreting in ovo data and the necessity of further research into the suitability of the in ovo model for evaluating different classes of radiotracers.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.