Blocking Studies to Evaluate Receptor-Specific Radioligand Binding in the CAM Model by PET and MR Imaging

Abstract

Inhibition studies in small animals are the standard for evaluating the specificity of newly developed drugs, including radiopharmaceuticals. Recently, it has been reported that the tumor accumulation of radiotracers can be assessed in the chorioallantoic membrane (CAM) model with similar results to experiments in mice, such contributing to the 3Rs principles (reduction, replacement, and refinement). However, inhibition studies to prove receptor-specific binding have not yet been performed in the CAM model. Thus, in the present work, we analyzed the feasibility of inhibition studies in ovo by PET and MRI using the PSMA-specific ligand [18F]siPSMA-14 and the corresponding inhibitor 2-PMPA. A dose-dependent blockade of [18F]siPSMA-14 uptake was successfully demonstrated by pre-dosing with different inhibitor concentrations. Based on these data, we conclude that the CAM model is suitable for performing inhibition studies to detect receptor-specific binding. While in the later stages of development of novel radiopharmaceuticals, testing in rodents will still be necessary for biodistribution analysis, the CAM model is a promising alternative to mouse experiments in the early phases of compound evaluation. Thus, using the CAM model and PET and MR imaging for early pre-selection of promising radiolabeled compounds could significantly reduce the number of animal experiments.

Editorial for Special Issue: The Chorioallantoic Membrane (CAM) Model—Traditional and State-of-the Art Applications: The 1st International CAM Conference

“…In another study, it was reported that radiotracers specifically accumulate in the ovografts and can be followed in the CAM model using positron emission tomography and magnetic resonance scanning [7]. Moreover, the specific target-binding of radiopharmaceuticals was assessed in MRI using specific blocking agents [8]. Consequently, the authors suggested the CAM model as an effective pre-screening assay to detect the bio-distribution of novel radiolabeled compounds saving animal experiments in mice.…”

CAM-Xenograft Model Provides Preclinical Evidence for the Applicability of [68Ga]Ga-Pentixafor in CRC Imaging

“…In the last 10 years, the interest of the nuclear imaging community in this model has increased [ 36 ]. Imaging studies were performed using different radiotracers, cancer models, and imaging modalities [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. There are already initial studies showing the comparability of the in ovo model to mice [ 40 , 45 ], suggesting good transferability of results to other animal species.…”