Login Register Cart 0
Generic placeholder image

Current Radiopharmaceuticals

Editor-in-Chief

ISSN (Print): 1874-4710
ISSN (Online): 1874-4729

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

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

Author(s): Urszula Karczmarczyk, Piotr Ochniewicz*, Ewa Laszuk, Kamil Tomczyk and Piotr Garnuszek

Volume 15, Issue 1, 2022

Published on: 28 May, 2021

Page: [84 - 91] Pages: 8

DOI: 10.2174/1874471014666210528124953

Price: $65

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, mice strain, biodistribution, radiopharmaceutical, quality control requirements, radioactive isotopes.

« Previous
Graphical Abstract

[1]
Pharmaceutical Medicine and Translational Clinical Research; Vohora, D.; Singh, G. , Eds.; A cademic Press, 2018.
[http://dx.doi.org/10.1016/B978-0-12-802103-3.00002-X]
[2]
The Pharmaceutical Journal, PJ. Available from: URL’online, 20068196, 2015.
[3]
Available from: https://www.policymed.com/2014/12/a- tough-road-cost-to-develop-one-new-drug-is-26-billion-approval-rate- for-drugs-entering-clinical-de.htmlAccessed January 05, 2021
[4]
Wikipedia. Available from: https://encyklopedia.pwn.plAccessed January 05, 2021
[5]
Festing, S.; Wilkinson, R. The ethics of animal research. Talking Point on the use of animals in scientific research. EMBO Rep., 2007, 8(6), 526-530.
[http://dx.doi.org/10.1038/sj.embor.7400993] [PMID: 17545991]
[6]
People for the Ethical Treatment of Animals. Available from: https://www.peta.org/issues/animals-used-for-experimentation/animal-testing-101Accessed May 01 2020
[7]
Joffe, A.R.; Bara, M.; Anton, N.; Nobis, N. The ethics of animal research: A survey of the public and scientists in North America. BMC Med. Ethics, 2016, 17, 17-26.
[http://dx.doi.org/10.1186/s12910-016-0100-x] [PMID: 27025215]
[8]
Holden, J. Of mice and medicine: The ethics of animal research Lab work that involves animals is controversial but such research is heavily regulated. The Irish times, 2016. Available from: https://irishtimes.com
[9]
Olszewski, J.; Jabłecka, A.; Piątek, J.; Samborski, W.; Zawadziński, J. Badania eksperymentalne – przedkliniczne na zwierzętach. Nowiny Lekarskie, 2011, 80(3), 219-221.
[10]
Derlin, T.; Schmuck, S.; Juhl, C.; Teichert, S.; Zörgiebel, J.; Wester, H.J.; Schneefeld, S.M.; Walte, A.C.A.; Thackeray, J.T.; Ross, T.L.; Bengel, F.M. Imaging characteristics and first experience of [68Ga]THP-PSMA, a novel probe for rapid kit-based Ga-68 labeling and PET imaging: comparative analysis with [68Ga]PSMA I&T. Mol. Imaging Biol., 2018, 20(4), 650-658.
[http://dx.doi.org/10.1007/s11307-018-1160-8] [PMID: 29344901]
[11]
Kowalczyk, P.; Biała, D.; Szczepanik, M.; Majewska-Szczepanik, M. Modele myszy Z niedoborami odporności: Charakterystyka I zastosowanie. KOSMOS Problemy Nauk Biologicznych, 2019, 68, 375-387.
[http://dx.doi.org/10.36921/kos.2019_2603]
[12]
Waterston, R.H.; Lindblad-Toh, K.; Birney, E.; Rogers, J.; Abril, J.F.; Agarwal, P.; Agarwala, R.; Ainscough, R.; Alexandersson, M.; An, P.; Antonarakis, S.E.; Attwood, J.; Baertsch, R.; Bailey, J.; Barlow, K.; Beck, S.; Berry, E.; Birren, B.; Bloom, T.; Bork, P.; Botcherby, M.; Bray, N.; Brent, M.R.; Brown, D.G.; Brown, S.D.; Bult, C.; Burton, J.; Butler, J.; Campbell, R.D.; Carninci, P.; Cawley, S.; Chiaromonte, F.; Chinwalla, A.T.; Church, D.M.; Clamp, M.; Clee, C.; Collins, F.S.; Cook, L.L.; Copley, R.R.; Coulson, A.; Couronne, O.; Cuff, J.; Curwen, V.; Cutts, T.; Daly, M.; David, R.; Davies, J.; Delehaunty, K.D.; Deri, J.; Dermitzakis, E.T.; Dewey, C.; Dickens, N.J.; Diekhans, M.; Dodge, S.; Dubchak, I.; Dunn, D.M.; Eddy, S.R.; Elnitski, L.; Emes, R.D.; Eswara, P.; Eyras, E.; Felsenfeld, A.; Fewell, G.A.; Flicek, P.; Foley, K.; Frankel, W.N.; Fulton, L.A.; Fulton, R.S.; Furey, T.S.; Gage, D.; Gibbs, R.A.; Glusman, G.; Gnerre, S.; Goldman, N.; Goodstadt, L.; Grafham, D.; Graves, T.A.; Green, E.D.; Gregory, S.; Guigó, R.; Guyer, M.; Hardison, R.C.; Haussler, D.; Hayashizaki, Y.; Hillier, L.W.; Hinrichs, A.; Hlavina, W.; Holzer, T.; Hsu, F.; Hua, A.; Hubbard, T.; Hunt, A.; Jackson, I.; Jaffe, D.B.; Johnson, L.S.; Jones, M.; Jones, T.A.; Joy, A.; Kamal, M.; Karlsson, E.K.; Karolchik, D.; Kasprzyk, A.; Kawai, J.; Keibler, E.; Kells, C.; Kent, W.J.; Kirby, A.; Kolbe, D.L.; Korf, I.; Kucherlapati, R.S.; Kulbokas, E.J.; Kulp, D.; Landers, T.; Leger, J.P.; Leonard, S.; Letunic, I.; Levine, R.; Li, J.; Li, M.; Lloyd, C.; Lucas, S.; Ma, B.; Maglott, D.R.; Mardis, E.R.; Matthews, L.; Mauceli, E.; Mayer, J.H.; McCarthy, M.; McCombie, W.R.; McLaren, S.; McLay, K.; McPherson, J.D.; Meldrim, J.; Meredith, B.; Mesirov, J.P.; Miller, W.; Miner, T.L.; Mongin, E.; Montgomery, K.T.; Morgan, M.; Mott, R.; Mullikin, J.C.; Muzny, D.M.; Nash, W.E.; Nelson, J.O.; Nhan, M.N.; Nicol, R.; Ning, Z.; Nusbaum, C.; O’Connor, M.J.; Okazaki, Y.; Oliver, K.; Overton-Larty, E.; Pachter, L.; Parra, G.; Pepin, K.H.; Peterson, J.; Pevzner, P.; Plumb, R.; Pohl, C.S.; Poliakov, A.; Ponce, T.C.; Ponting, C.P.; Potter, S.; Quail, M.; Reymond, A.; Roe, B.A.; Roskin, K.M.; Rubin, E.M.; Rust, A.G.; Santos, R.; Sapojnikov, V.; Schultz, B.; Schultz, J.; Schwartz, M.S.; Schwartz, S.; Scott, C.; Seaman, S.; Searle, S.; Sharpe, T.; Sheridan, A.; Shownkeen, R.; Sims, S.; Singer, J.B.; Slater, G.; Smit, A.; Smith, D.R.; Spencer, B.; Stabenau, A.; Stange-Thomann, N.; Sugnet, C.; Suyama, M.; Tesler, G.; Thompson, J.; Torrents, D.; Trevaskis, E.; Tromp, J.; Ucla, C.; Ureta-Vidal, A.; Vinson, J.P.; Von Niederhausern, A.C.; Wade, C.M.; Wall, M.; Weber, R.J.; Weiss, R.B.; Wendl, M.C.; West, A.P.; Wetterstrand, K.; Wheeler, R.; Whelan, S.; Wierzbowski, J.; Willey, D.; Williams, S.; Wilson, R.K.; Winter, E.; Worley, K.C.; Wyman, D.; Yang, S.; Yang, S.P.; Zdobnov, E.M.; Zody, M.C.; Lander, E.S. Mouse Genome Sequencing Consortium. Initial sequencing and comparative analysis of the mouse genome. Nature, 2002, 420(6915), 520-562.
[http://dx.doi.org/10.1038/nature01262] [PMID: 12466850]
[13]
Cui, S.; Chesson, C.; Hope, R. Genetic variation within and between strains of outbred Swiss mice. Lab. Anim., 1993, 27(2), 116-123.
[http://dx.doi.org/10.1258/002367793780810397] [PMID: 8501892]
[14]
Chia, R.; Achilli, F.; Festing, M.F.; Fisher, E.M. The origins and uses of mouse outbred stocks. Nat. Genet., 2005, 37(11), 1181-1186.
[http://dx.doi.org/10.1038/ng1665] [PMID: 16254564]
[15]
Lehoczky, J.A.; Cai, W.W.; Douglas, J.A.; Moran, J.L.; Beier, D.R.; Innis, J.W. Description and genetic mapping of Polypodia: An X-linked dominant mouse mutant with ectopic caudal limbs and other malformations. Mamm. Genome, 2006, 17(9), 903-913.
[http://dx.doi.org/10.1007/s00335-006-0041-7] [PMID: 16964440]
[16]
Brown, J.A.; Chua, S.C., Jr; Liu, S.M.; Andrews, M.T.; Vandenbergh, J.G. Spontaneous mutation in the db gene results in obesity and diabetes in CD-1 outbred mice. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2000, 278(2), R320-R330.
[http://dx.doi.org/10.1152/ajpregu.2000.278.2.R320] [PMID: 10666131]
[17]
ICH Topic M3(R2) document “non-clinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals”. Available from: www.fda.govAccessed January 05, 2021
[18]
ICH Topic S9 Document “Non-clinical evaluation for anticancer pharmaceuticals”. Available from: www.fda.govAccessed January 05, 2021
[19]
ICH Topic S6(R1) Document “Preclinical safety evaluation of biotechnology-derived pharmaceuticals”. Available from: www.fda.govAccessed January 05, 2021
[20]
Festing, M.F.W. Inbred strains should replace outbred stocks in toxicology, safety testing, and drug development. Toxicol. Pathol., 2010, 38(5), 681-690.
[http://dx.doi.org/10.1177/0192623310373776] [PMID: 20562325]
[21]
Dube, Ph. The importance of genetic background in mouse models. Available from: www. biocompare.com/Bench-Tips/341470-The-Importance-of-Genetic-Background-in-Mouse-Models/Accessed January 05, 2021
[22]
Maurin, M.; Sikora, A.; Wyczółkowska, M.; Karczmarczyk, U.; Garnuszek, P. In vitro and in vivo evaluation of the new 99mTc labelled PSMA tracers in prostate cancer diagnosis. Eur. J. Nucl. Med. Mol. Imaging, 2019, 46, 15.
[http://dx.doi.org/10.1007/s00259-019-04486-2]
[23]
Garnuszek, P.; Janota, B.; Jaron, A.W.; Maurin, Micha.; Wyczółkowska, M.; Pijarowska-Kruszyna, J.; Radzik, M.; Sikora, A.E.; Karczmarczyk, U PSMA inhibitor derivatives for labelling with 99mTc via HYNIC, a radiopharmaceutical kit, radiopharmaceutical preparations and their use in prostate cancer diagnostics. European Patent 3721907A1, U.S. Patent 2020324000A1, 2021.
[24]
The Jackson Laboratory. Available from: https://www.jax.org/strainAccessed January 05, 2021
[25]
Mohan, R.; Randall, R.; Hawkins, A. Nuclear medicine imaging Encyclopaedia of Gastroenterology; Elsevier, 2004, pp. 748-754.
[http://dx.doi.org/10.1016/B0-12-386860-2/00512-8]
[26]
Kiige, S.G.; Mutiso, J.M.; Laban, L.T.; Khayeka-Wandabwa, C.; Anjili, C.O.; Ingonga, J.; Gicheru, M.M.A. F1 cross-breed between susceptible BALB/c and resistant Swiss mice infected with Leishmania major exhibit an intermediate phenotype for lesion sizes and type 1 cytokines but show low level of total IgG antibodies. Scand. J. Immunol., 2014, 79(5), 283-291.
[http://dx.doi.org/10.1111/sji.12159] [PMID: 24498914]
[27]
Howard, J.G.; Hale, C.; Liew, F.Y. Immunological regulation of experimental cutaneous leishmaniasis. III. Nature and significance of specific suppression of cell-mediated immunity in mice highly susceptible to Leishmania tropica. J. Exp. Med., 1980, 152(3), 594-607.
[http://dx.doi.org/10.1084/jem.152.3.594] [PMID: 6447751]
[28]
Iskandar, S.S.; Jennette, J.C.; Wilkman, A.S.; Becker, R.L. Interstrain variations in nephritogenicity of heterologous protein in mice. Lab. Invest., 1982, 46(3), 344-351.
[PMID: 6460898]
[29]
Gallyamov, M.; Meyrick, D.; Barley, J.; Lenzo, N. Renal outcomes of radioligand therapy: Experience of 177lutetium-prostate-specific membrane antigen ligand therapy in metastatic castrate-resistant prostate cancer. Clin. Kidney J., 2019, 13(6), 1049-1055.
[http://dx.doi.org/10.1093/ckj/sfz101] [PMID: 33391748]
[30]
Nishioka, Y. Y-chromosomal DNA polymorphism in mouse inbred strains. Genet. Res., 1987, 50(1), 69-72.
[http://dx.doi.org/10.1017/S0016672300023351] [PMID: 2888708]
[31]
Nishioka, Y.; Lamothe, E. Evolution of a mouse Y chromosomal sequence flanked by highly repetitive elements. Genome, 1987, 29(2), 380-383.
[http://dx.doi.org/10.1139/g87-065] [PMID: 3034726]
[32]
Bishop, C.E.; Boursot, P.; Baron, B.; Bonhomme, F.; Hatat, D. Most classical Mus musculus domesticus laboratory mouse strains carry a Mus musculus musculus Y chromosome. Nature, 1985, 315(6014), 70-72.
[http://dx.doi.org/10.1038/315070a0] [PMID: 2986012]
[33]
Vanlerberghe, F.; Dod, B.; Boursot, P.; Bellis, M.; Bonhomme, F. Absence of Y-chromosome introgression across the hybrid zone between Mus musculus domesticus and Mus musculus musculus. Genet. Res., 1986, 48(3), 191-197.
[http://dx.doi.org/10.1017/S0016672300025003] [PMID: 3569903]
[34]
Grounds, M.D.; McGeachie, J.K. A comparison of muscle precursor replication in crush-injured skeletal muscle of Swiss and BALBc mice. Cell Tissue Res., 1989, 255(2), 385-391.
[http://dx.doi.org/10.1007/BF00224122] [PMID: 2924339]
[35]
Festing, M.F.W. Improving toxicity screening and drug development by using genetically defined strains. Methods Mol. Biol., 2010, 602, 1-21.
[http://dx.doi.org/10.1007/978-1-60761-058-8_1] [PMID: 20012389]
[36]
Nonnekens, J.; Schottelius, M. “Luke! Luke! Don’t! It’s a trap!”-spotlight on bias in animal experiments in nuclear oncology. Eur. J. Nucl. Med. Mol. Imaging, 2020, 47(5), 1024-1026.
[http://dx.doi.org/10.1007/s00259-020-04717-x] [PMID: 32040610]
[37]
Ritskes-Hoitinga, M.; Leenaars, M.; Avey, M.; Rovers, M.; Scholten, R. Systematic reviews of preclinical animal studies can make significant contributions to health care and more transparent translational medicine. Cochrane Database Syst. Rev., 2014, (3), ED000078.
[http://dx.doi.org/10.1002/14651858.ED000078] [PMID: 24719910]
[38]
Percie du Sert, N.; Hurst, V.; Ahluwalia, A.; Alam, S.; Avey, M.T.; Baker, M.; Browne, W.J.; Clark, A.; Cuthill, I.C.; Dirnagl, U.; Emerson, M.; Garner, P.; Holgate, S.T.; Howells, D.W.; Karp, N.A.; Lazic, S.E.; Lidster, K.; MacCallum, C.J.; Macleod, M.; Pearl, E.J.; Petersen, O.; Rawle, F.; Peynolds, P.; Rooney, K.; Sena, E.S.; Silberberg, S.D.; Steckler, T. Wurbel. H. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol., 2020, 18(7), e3000411.
[http://dx.doi.org/10.1371/journal.pbio.3000411] [PMID: 32663221]

Rights & Permissions Print Cite
Article Metrics
18
1
© 2024 Bentham Science Publishers | Privacy Policy