Practical considerations for navigating the regulatory landscape of non-clinical studies for clinical translation of radiopharmaceuticals.

BACKGROUND: The development of radiopharmaceuticals requires extensive evaluation before they can be applied in a diagnostic or therapeutic setting in Nuclear Medicine. Chemical, radiochemical, and pharmaceutical parameters must be established and verified to ensure the quality of these novel products. MAIN BODY: To provide supportive evidence for the expected human in vivo behaviour, particularly related to safety and efficacy, additional tests, often referred to as "non-clinical" or "preclinical" are mandatory. This document is an outcome of a Technical Meeting of the International Atomic Energy Agency. It summarises the considerations necessary for non-clinical studies to accommodate the regulatory requirements for clinical translation of radiopharmaceuticals. These considerations include non-clinical pharmacology, radiation exposure and effects, toxicological studies, pharmacokinetic modelling, and imaging studies. Additionally, standardisation of different specific clinical applications is discussed. CONCLUSION: This document is intended as a guide for radiopharmaceutical scientists, Nuclear Medicine specialists, and regulatory professionals to bring innovative diagnostic and therapeutic radiopharmaceuticals into the clinical evaluation process in a safe and effective way.

λ-Eye: a high-sensitivity γ imaging probe for axillary sentinel lymph node mapping.

OBJECTIVE: The aim of this study is the construction and performance evaluation of 'λ-eye', a γ imaging probe, optimized in terms of sensitivity for sentinel lymph node mapping. The optimization of the probe is based on theoretical models and simulation results that were presented in a previous study of our group. In this work, the construction of the probe, the experimental confirmation of the simulation results, and the evaluation of its performance with phantoms and lymph node imaging in small animals are presented. METHODS: The system's spatial and energy resolution, sensitivity, and count rate performance were measured using phantoms. The values of the integral and differential uniformity in the useful field-of-view and in the central field-of-view were also calculated. Finally, a proof-of-concept animal experiment was conducted for the imaging of the lymph nodes of normal mice. RESULTS: The system's energy resolution was measured as 36±2% and the spatial resolution was 2.2 mm at 2 mm source-collimator distance. The values of the integral uniformity and differential uniformity in the useful field-of-view and in the central field-of-view were found to be 5.2, 2.1, 1.7, and 0.75%, respectively. Finally, the lymph nodes of normal mice were clearly imaged with a 10 s acquisition time. CONCLUSION: The 'λ-eye', used for sentinel lymph node mapping, provides a combination of high sensitivity (∼1.5 counts/s/kBq) and good spatial resolution (∼6 mm full-width of the half-maximum at 20 mm and ∼10 mm full-width of the half-maximum at 50 mm distance). Its compact size (40 mm×40 mm×70 mm) allows its use during surgery and/or for the detailed scan of a suspicious region.