How does the Selection of Laboratory Mice Affect the Results of Physiological Distribution of Radiopharmaceuticals?

Abstract

Background: The choice of mice strain can significantly influence the physiological distribution and may lead to an inadequate assessment of the radiopharmaceutical properties.

Objective: This work aims to present how the legal requirements that apply to radiopharmaceuticals contained in the various guidelines determine the choice of the mouse strain for quality control and preclinical studies and affect the results of physiological distribution.

Methods: Swiss and BALB/c mice were chosen as commonly used strains in experiments for research and quality control purposes. Radiopharmaceuticals, i.e., preparations containing one or more radioactive isotopes in their composition, are subject to the same legal regulations at every stage of the research, development and routine quality control as all other medicines. Therefore, in vivo experiments are to be carried out to confirm the pharmacological properties and safety. Moreover, if a radiopharmaceutical's chemical structure is unknown or complex and impossible to be determined by physicochemical methods, an analysis of physiological distribution in a rodent animal model needs to be performed.

Results: In our studies, thirty-six mice (Swiss n=18, BALB/c n=18) were randomly divided into six groups and injected with the following radiopharmaceuticals: [^99mTc]Tc-Colloid, [^99mTc]Tc-DTPA and [^99mTc]Tc-EHIDA. Measurement of physiological distribution was conducted following the requirements of European Pharmacopoeia (Ph. Eur.) monograph 0689, internal instructions and the United States Pharmacopeia (USP) monograph. Additionally, at preclinical studies, ten mice (Swiss n=5, BALB/c n=5) were injected with the new tracer [^99mTc]Tc-PSMA-T4, and its physiological distribution has been compared. The p-value <0.05 proved the statistical significance of the radiopharmaceutical physiological distribution.

Conclusion: We claim that mice strain choice can significantly influence the physiological distribution and may lead to inaccurate quality control results and incomprehensible interpretation of the results from preclinical in vivo studies of a new radiopharmaceutical.

Keywords: Preclinical study; biodistribution; mice strain; quality control requirements; radioactive isotopes; radiopharmaceutical.