Preclinical in vivo dosimetry of healthy tissues in radiopharmaceutical therapy: implementation of a physiologically realistic mouse eye model in GATE.

BACKGROUND

Targeted radionuclide therapy is a rapidly growing treatment modality that has shown great promise in managing metastatic cancers. However, the affinity of certain radiopharmaceuticals for off-target healthy tissues necessitates accurate dosimetric evaluations. This is especially the case for [131I]ICF01012, an experimental radiopharmaceutical used for advanced melanoma targeted radionuclide therapy, which targets melanin in pigmented tumors and metastases but also in melanized healthy tissues, including sensitive structures such as the retinal pigment epithelium. This study aimed to create the first anatomically precise, voxel-based mouse eye model to facilitate microdosimetric evaluations in the context of targeted radionuclide therapy. A voxelized model of the mouse eye was constructed using high-resolution MRI and SIMS imaging data from C57Bl/6J mice. The biodistribution of radioactivity in the eyes was assessed ex vivo by gamma counting. GATE Monte Carlo simulations were employed to calculate the S-values of the intraocular structures. Particular attention was given to the absorbed dose by the retina considering its proximity to the retinal pigment epithelium, which contains melanin.

RESULTS

SIMS imaging revealed an increased iodine-127 signal in melanin-rich regions, particularly the retinal pigment epithelium and choroid. S values were obtained for all relevant source and target regions of the eye. Time-dependent biodistribution analysis of radioactivity revealed persistent retention of the radiotracer up to 21 days after injection. The retinal pigment epithelium received the highest dose, 24.14 Gy.MBq⁻¹, corresponding to an estimated absorbed dose by the retina of 6.91 Gy.MBq⁻¹.

CONCLUSION

This work presents a novel dosimetry model for the mouse eye, providing essential insights into the exposure of melanin-rich tissues to iodine-131 radiation. Such models are necessary for optimizing therapeutic efficacy while minimizing toxicity in preclinical studies.