Radiopharmaceutical preclinical investigation: an accurate and multidisciplinary approach

Abstract

Background: The development of less expensive and pivotal methodologies, capable to support the researchers in the radiopharmaceutical pre-clinical investigations could provide a crucial incentive for developing biomedical research involved in the realization of tailored target therapies. Objective: The aim of this pilot study was to evaluate the capability of a digital autoradiography system equipped with a laser scanning device to perform [18F]choline biodistribution evaluation in a xenograft mouse model of prostate cancer. Methods: PC3 prostate cancer cells were used to develop xenografts in NOD/SCID mice. The biodistribution of the radiopharmaceutical was evaluated at 30,60 and 120 min after injection in excised organs by using a digital autoradiography system equipped with super resolution laser screen. Histological and immunohistochemical analysis were performed to correlate the [18F]choline uptake with morphological and molecular tumours characteristics. Results: Data here reported clearly indicate the possibility to perform accurate biodistribution studies by using the digital autoradiographic system equipped with a super resolution screen. Specifically, a significant increase in the [18F]choline inhibitor uptake in PC3 tumours as compared to heart, bowel, liver and kidney at both 30 and 60 min was observed. More important, the digital autoradiographic system showed signal uptake almost exclusively in the PC3 tumors at 60 min post-injection. Noteworthy, immunohistochemical analysis demonstrated a strong overlapping between the [18F]choline uptake and the proliferation index (Ki67 expression). Conclusions: The use of autoradiography system in pre-clinical investigations could shed new light on the molecular mechanisms that orchestrate the tissues damage induced by therapeutical radiopharmaceuticals.