SMALL ANIMAL MODEL IN THE DEVELOPMENT OF RADIOPHARMACEUTICALS - THE STEP FORWARD TOCLINICAL STUDIES
Date Issued
2022
Author(s)
Janevik Ivanovska, Emilija
Aleksovski, Boris
Darkovska Serafimovska, Marija
Smilkov, Katarina
Gjorgieva Ackova, Darinka
Arev, Marija
Apostolova, Paulina
Balogh, Lajos
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.
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.
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