SMALL ANIMAL MODEL IN THE DEVELOPMENT OF RADIOPHARMACEUTICALS - THE STEP FORWARD TOCLINICAL STUDIES

Abstract

Experimental design is a critical component for the success of research activities involving development and evaluation of new radiopharmaceuticals. Experimental animal models have substantially contributed to a better understanding of mechanisms of disease and show the novel approaches in imaging and image analysis were equally important to meet the challenges of analyzing the complex mechanisms underlying pathophysiological processes in vivo. Proper animal models are key factors for successful pharmaceutical and medicinal experiments. To reduce animal number for ethical and  nancial reasons, cost-ef cient methods where high quantities of data are achieved fast are optimal. Biodistribution and pharmacokinetics studies diagnostic or therapeutic radiopharmaceuticals by SPECT or PET imaging followed by post mortem analysis in diseases model gives a good start point for further steps toward clinical applications. In this presentation, targeting properties, biodistribution and pharmacokinetics of different molecules, as potential radiopharmaceuticals have been studied in small animal models using suitable imaging modalities and post mortem analysis. The following experimentally designed animal models have been introduced in our work so far as an essential part in the development of new radiopharmaceutical products and quality control of existing radiopharmaceutical products. Rat models were used to establish: stasis-induced thrombus in the femoral vein after injection of thromboplastin to demonstrate Deep Venous Thrombosis; induced amyloidosis by multiple application of beta2-microglobulin for determination of the existence of the depositing osteoarticular tissues, condition associated with hemodialysis in patients with chronic kidney diseases; collagen-induced arthritis as a model of in ammatory arthritis; bacterial abscesses by the injection of Staphylococcus aureus. Mouse models were used for: in vivo evaluation of the radiolabelled conjugated antibodies in normal Balb/c mice and nude mice xenografts; per os administration of iodine labeled BSA loaded microspheres to show the strong adjuvant effect by inducing IgA secretion at the genito-urinary mucosa; athymic nude mice tumor bearning to demonstratespeci ty of pre-targeting technique referred to the Af nity Enhancement System (AES) uses bispeci c antibodies and radiolabeled bivalent haptens. The use of experimental animal models in the design of new drugs including radiopharmaceuticals is a key part of preclinical trials. Usually this approach can not fully replicate human disease or the varied and complex physical and psychological manifestations of human conditions. For these reasons the process of experimental design should be carried out routinely to ensure the generation of valid, reproducible and published data.