Small animal model in the development of radiopharmaceuticals - the step forward to clinical studies

Janevik-Ivanovska, Emilija and Gjorgoski, Icko and Aleksovski, Boris and Tripunoski, Toni and Darkovska-Serafimovska, Marija and Smilkov, Katarina and Gjorgieva Ackova, Darinka and Arev, Marija and Apostolova, Paulina and Baloch, Lajos (2022) Small animal model in the development of radiopharmaceuticals - the step forward to clinical studies. In: 9th International Scientific Meeting Days of Veterinary Medicine, 22-25 Sept 2022, Ohrid, Macedonia.

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Experimental design is obviously a critical component for the success of any research activities concerning development and evaluation of new radiopharmaceuticals.
The development of new generation of radiolabeled molecules and technologies (SPECT/PET) for delivery of radioisotopes to the disease-target-sites with a high degree of precision, recognition, and target selectivity can facilitate mapping of the biochemistry of the metabolic organ function, visualizing the molecular biology of cell function, and zooming in on gene function for delineating differences in molecular biology of normal health from disease, in animals to humans.
This type of imaging refines diagnostic differentiation at molecular or metabolic levels between health and disease, and among various diseases, often leading to more effective therapy.
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.
The appropriate animal models are not only helpful in finally proving longstanding hypotheses for development for radiopharmaceuticals but have rather been used to discover new and previously unexpected mechanisms and causal relationships.
Proper animal models are key factor in successful pharmaceutical or medicinal experiment. To reduce animal number for ethical and financial reasons, cost-efficient 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 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, with the intention of showing the importance of establishing procedures and protocols for experimental studies as an essential part in the development of new radiopharmaceutical products and quality control of existing radiopharmaceutical products.
The rats were used for establishing of:
- stasis-induced thrombus in the femoral vein after injection of thromboplastin to demonstrate Deep Venous Thrombosis using radiolabeled Tirofiban - GPIIb/IIIa inhibitor;
- 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 inflammatory arthritis
- bacterial abscesses by the injection of Staphylococcus aureus
Mice animal 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 demonstrate specifity of pretargeting technique referred to the Affinity Enhancement System (AES) uses bispecific 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 never 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.

Item Type: Conference or Workshop Item (Poster)
Subjects: Medical and Health Sciences > Other medical sciences
Divisions: Faculty of Medical Science
Depositing User: Marija Arev
Date Deposited: 30 Jan 2023 12:17
Last Modified: 30 Jan 2023 12:17

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