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

Area of Science:

• Nuclear Medicine
• Radiopharmaceutical Development
• In Vivo Imaging

Background:

• Inhibition studies in animals are standard for evaluating drug specificity, including radiopharmaceuticals.
• The chorioallantoic membrane (CAM) model shows promise for assessing radiotracer tumor accumulation, aligning with the 3Rs principles.
• Inhibition studies to confirm receptor-specific binding have not been established in the CAM model.

Purpose of the Study:

• To evaluate the feasibility of conducting inhibition studies in ovo using the CAM model.
• To assess receptor-specific binding of radiotracers using PET and MRI in the CAM model.
• To establish the CAM model as a viable alternative for early-stage radiopharmaceutical evaluation, reducing reliance on animal models.

Main Methods:

• Utilized the prostate-specific membrane antigen (PSMA)-specific ligand [18F]siPSMA-14 and its inhibitor 2-PMPA.
• Employed Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) for in ovo imaging.
• Administered varying concentrations of the inhibitor to assess dose-dependent effects on radiotracer uptake.

Main Results:

• Successfully demonstrated a dose-dependent blockade of [18F]siPSMA-14 uptake in the CAM model.
• Confirmed the suitability of the CAM model for performing inhibition studies to detect receptor-specific binding.
• Showcased the potential of PET and MRI in the CAM model for evaluating radiopharmaceutical binding characteristics.

Conclusions:

• The CAM model is suitable for inhibition studies, confirming receptor-specific binding of radiotracers.
• This in ovo model offers a promising alternative to mouse experiments in the early phases of radiopharmaceutical development.
• Implementing the CAM model with PET and MRI can significantly reduce the number of animal experiments required for compound pre-selection.