Comparison of Quantification of Target-Specific Accumulation of [(18)F]F-siPSMA-14 in the HET-CAM Model and in Mice Using PET/MRI

SIMPLE SUMMARY: Animal studies are essential for the development of new radiopharmaceuticals to determine specific accumulation and biodistribution. Alternative models, such as the HET-CAM model, offer the possibility of reducing animal experiments in accordance with the 3Rs principles. Accurate quantification of tumor accumulation of a PSMA-specific ligand in the HET-CAM model and comparison with corresponding animal experiments was performed using the imaging modalities PET and MRI. It was demonstrated that the HET-CAM model leads to comparable results and is suitable as an alternative to animal experiments for the initial assessment of target-specific binding of novel radiopharmaceuticals. However, as evaluation of biodistribution in ovo is still limited, further animal experiments with promising compounds are mandatory. ABSTRACT: Assessment of biodistribution and specific tumor accumulation is essential for the development of new radiopharmaceuticals and requires animal experiments. The HET-CAM (hens-egg test—chorioallantoic membrane) model can be used in combination with the non-invasive imaging modalities PET and MRI for pre-selection during radiopharmaceutical development to reduce the number of animal experiments required. Critical to the acceptance of this model is the demonstration of the quantifiability and reproducibility of these data compared to the standard animal model. Tumor accumulation and biodistribution of the PSMA-specific radiotracer [(18)F]F-siPSMA-14 was analyzed in the chick embryo and in an immunodeficient mouse model. Evaluation was based on MRI and PET data in both models. γ-counter measurements and histopathological analyses complemented these data. PSMA-specific accumulation of [(18)F]F-siPSMA-14 was successfully demonstrated in the HET-CAM model, similar to the results obtained by mouse model studies. The combination of MR and PET imaging allowed precise quantification of peptide accumulation, initial assessment of biodistribution, and accurate determination of tumor volume. Thus, the use of the HET-CAM model is suitable for the pre-selection of new radiopharmaceuticals and potentially reduces animal testing in line with the 3Rs principles of animal welfare.