Evaluation of the EPR Effect in the CAM-Model by Molecular Imaging with MRI and PET Using ⁸⁹Zr-Labeled HSA

Area of Science:

• Nuclear medicine
• Preclinical research
• Biomedical imaging

Background:

• Mouse models are standard for radioligand biodistribution studies but raise ethical concerns.
• The chorioallantoic membrane (CAM) model offers a potential alternative aligned with the 3Rs principles.
• The CAM model's utility for macromolecule biodistribution and the EPR effect requires further validation.

Purpose of the Study:

• To evaluate the CAM model's suitability for assessing macromolecule biodistribution and the EPR effect.
• To compare macromolecule accumulation in tumors using the CAM model versus traditional mouse xenograft models.
• To utilize 89Zr-labeled human serum albumin ([89Zr]Zr-DFO-HSA) for PET and MRI imaging in both models.

Main Methods:

• Administered [89Zr]Zr-DFO-HSA to chicken embryos (CAM model) and SCID mice with TZM-bl and PC-3 tumors.
• Conducted dynamic PET and anatomical MRI scans over 24 hours.
• Performed ex vivo biodistribution analyses, histological staining, and autoradiography for verification.

Main Results:

• Tumor visualization was successful in both CAM and mouse models using PET imaging.
• Albumin influx into tumors did not significantly differ between the CAM and mouse models.
• Demonstrated accumulation and retention of human serum albumin (HSA) in tumors, indicating the EPR effect in both models.

Conclusions:

• The CAM model is a viable alternative to mouse models for initial studies of novel radiolabeled macromolecules.
• This finding supports the application of the CAM model in preclinical research, adhering to the 3Rs principles.
• The CAM model effectively replicates macromolecule biodistribution and EPR phenomena observed in mouse xenografts.