Radiopharmaceutical preclinical investigation: an accurate and multidisciplinary approach

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.

Novel Biological and Molecular Characterization in Radiopharmaceutical Preclinical Design

In this study, the potential of a digital autoradiography system equipped with a super resolution screen has been evaluated to investigate the biodistribution of a 18F-PSMA inhibitor in a prostate cancer mouse model. Twelve double xenograft NOD/SCID mice (LNCAP and PC3 tumours) were divided into three groups according to post-injection time points of an 18F-PSMA inhibitor. Groups of 4 mice were used to evaluate the biodistribution of the radiopharmaceutical after 30-, 60- and 120-min post-injection. Data here reported demonstrated that the digital autoradiography system is suitable to analyse the biodistribution of an 18F-PSMA inhibitor in both whole small-animal bodies and in single organs. The exposure of both whole mouse bodies and organs on the super resolution screen surface allowed the radioactivity of the PSMA inhibitor distributed in the tissues to be detected and quantified. Data obtained by using a digital autoradiography system were in line with the values detected by the activity calibrator. In addition, the image obtained from the super resolution screen allowed a perfect overlap with the tumour images achieved under the optical microscope. In conclusion, biodistribution studies performed by the autoradiography system allow the microscopical modifications induced by therapeutic radiopharmaceuticals to be studied by comparing the molecular imaging and histopathological data at the sub-cellular level.