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DOI: 10.3413/Nukmed-0978-18-05
Normal Values of Thyroid Uptake of 99mTechnetium Pertechnetate SPECT in Mice with Respect to Age, Sex, and Circadian Rhythm
Normwerte für den Schilddrüsen Uptake von 99mTechnetium-Pertechnetat in Abhängigkeit von Alter, Geschlecht und circadianem Rhythmus bei der MausPublikationsverlauf
received:
28. Mai 2018
accepted:
08. August 2018
Publikationsdatum:
28. September 2018 (online)
Summary
Aim: The aim of this study was to establish normal values for thyroid uptake of 99mtechnetium pertechnetate (99mTcO4) as a function of age, sex and circadian rhythm in mice.
Methods: In 12 female (F) and 12 male (M) C57BL/6N mice, nine consecutive SPECT images of 10 min duration each were acquired as dynamic acquisitions beginning 5 min after intravenous injection of 80 MBq 99mTcO4. Each mouse was imaged in follow-up studies up to 24 months (A: 1 month; B: 3 months; C: 6 months; D: 12 months; E: 24 months). In order to assess for physiologic changes related to circadian rhythm, animals were imaged during light (sleeping phase, SP) as well as during night conditions (awake phase, AP). The percentage tracer uptake of the injected activity is expressed as median %ID.
Results: Female mice showed significantly higher uptake than males (F 1.6, M 1.1; p < 0.001). This effect was observed up to the age of 12 months: A (F 1.6, M 1.1; p < 0.001), B (F 1.7, M 1.1; p < 0.001), C (F 1.8, M 1.2; p < 0.001), D (F 1.6, M 1.2; p < 0.001), E (F 1.1, M 1.1; p = 0.79). Impact of age on uptake could be observed in females (p = 0.056) and was not present in males (p = 0.27). A significant effect of circadian rhythm could not be observed in females (SP 1.6, AP 1.7; p = 0.65) but in males (SP 1.2, AP 1.1; p = 0.02).
Conclusion: This study showed a significant influence of sex on thyroid 99mTcO4 uptake in mice. Sex was also a significant factor affecting age-related changes in uptake in female mice but not in males. In contrast, circadian rhythm had no relevant impact on 99mTcO4 uptake. Therefore, design of thyroid uptake studies in mice using 99mTcO4 should consider animal sex, and in females, age as significant factors affecting uptake.
Zusammenfassung
Ziel: Ziel dieser Studie war die Erhebung von Normwerten für den Schilddrüsen Uptake von 99mTechnetium-Pertechnetat (99mTcO4) in Abhängigkeit von Alter, Geschlecht und circadianem Rhythmus bei Mäusen.
Methoden: Bei 12 weiblichen (F) und 12 männlichen (M) C57BL/6N Mäusen wurden neun konsekutive SPECT Akquisitionen von jeweils 10 min Dauer 5 min nach intravenöser Injektion von 80 MBq 99mTcO4 durchgeführt. Jede Maus wurde mehrmals bis zu 24 Monaten untersucht (A: 1 Mo; B: 3 Mo; C: 6 Mo; D: 12 Mo; E: 24 Mo). Um Veränderungen auf Grund des circadianen Rhythmus zu erfassen wurden die Tiere während der Hellphase (Schlafphase, SP) sowie während der Dunkelphase (Wachphase, AP) untersucht. Der prozentuale Tracer Uptake ist als Median %ID der injizierten Aktivität aufgeführt.
Ergebnisse: Weibchen zeigten einen signifikant höheren Uptake als Männchen (F 1,6, M 1,1; p < 0,001). Dieser Effekt wurde bis zu einem Alter von 12 Mo beobachtet: A (F 1,16, M 1,1; p < 0,001), B (F 1,7, M 1,1; p < 0,001), C (F 1,8, M 1,2; p < 0,001), D (F 1,6, M 1,2; p < 0,001), E (F 1,1, M 1,1; p = 0,79). Ein altersabhängiger Einfluss zeigte sich bei Weibchen (p = 0,056), jedoch nicht bei Männchen (p = 0,27). Ein signifikanter Effekt des circadianen Rhythmus konnte bei Männchen (SP 1,2, AP 1,1; p = 0,02) nicht aber bei Weibchen (SP 1,6, AP 1,7; p = 0,65) beobachtet werden.
Schlussfolgerung: Diese Studie zeigt einen signifikant geschlechtsabhängigen Einfluss auf den Schilddrüsen Uptake von 99mTcO4 bei Mäusen. Im Gegensatz zu Männchen treten bei Weibchen altersabhängige Veränderungen im Uptake auf. Dagegen hat der circadiane Rhythmus keinen relevanten Einfluss. Folglich sollte bei dem Design von Schilddrüsenuntersuchungen mit 99mTcO4 bei der Maus Geschlecht und bei weiblichen Tieren auch Alter als signifikante Faktoren berücksichtigt werden.
Schlüsselwörter
Alter - Geschlecht - circadianer Rhythmus - SPECT - Technetium Uptake - Schilddrüse - ovarieller Zyklus* Both senior authors contributed equally to this work.
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References
- 1 Allen E. The oestrous cycle in the mouse. American Journal of Anatomy 1922; 30 (03) 297-371.
- 2 Arraj M, Lemmer B. Circadian rhythms in heart rate, motility, and body temperature of wild-type C57 and eNOS knock-out mice under light-dark, free-run, and after time zone transition. Chronobiol Int 2006; 23 (04) 795-812.
- 3 Atkins HL, Richards P. Assessment of thyroid function and anatomy with technetium-99m as pertechnetate. J Nucl Med 1968; 09 (01) 7-15.
- 4 Ayala C, Pennacchio GE, Soaje M. et al. Effects of thyroid status on NEI concentration in specific brain areas related to reproduction during the estrous cycle. Peptides 2013; 49: 74-80.
- 5 Balon HR, Silberstein EB, Meier DA. et al. Society of Nuclear Medicine Procedure Guideline for Thryoid Uptake Measurement. 2006
- 6 Beekman FJ, van der Have F, Vastenhouw B. et al. U-SPECT-I: a novel system for submillimeter-resolution tomography with radiolabeled molecules in mice. J Nucl Med 2005; 46 (07) 1194-1200.
- 7 Bianco AC, Anderson G, Forrest D. et al. American Thyroid Association Guide to investigating thyroid hormone economy and action in rodent and cell models. Thyroid 2014; 24 (01) 88-168.
- 8 Blumenthal HT. Aging processes in the endocrine glands of various strains of normal mice: relationship of hypophyseal activity to aging changes in other endocrine glands. J Gerontol 1955; 10 (03) 253-267.
- 9 Boschi F, Pagliazzi M, Rossi B. et al. Small-animal radionuclide luminescence imaging of thyroid and salivary glands with Tc99m-pertechnetate. J Biomed Opt 2013; 18 (07) 76005.
- 10 Brandt MP, Kloos RT, Shen DH. et al. Micro-single-photon emission computed tomography image acquisition and quantification of sodium-iodide symporter-mediated radionuclide accumulation in mouse thyroid and salivary glands. Thyroid 2012; 22 (06) 617-624.
- 11 Byers SL, Wiles MV, Dunn SL. et al. Mouse estrous cycle identification tool and images. PLoS One 2012; 07 (04) e35538.
- 12 Cambien B, Franken PR, Lamit A. et al. 99mTcO4--, auger-mediated thyroid stunning: dosimetric requirements and associated molecular events. PLoS One 2014; 09 (03) e92729.
- 13 Chai W, Yin X, Ren L. et al. Sodium/iodide symporter gene transfection increases radionuclide uptake in human cisplatin-resistant lung cancer cells. Clin Transl Oncol 2015; 17 (10) 795-802.
- 14 Diaz Brinton R. Minireview: translational animal models of human menopause: challenges and emerging opportunities. Endocrinology 2012; 153 (08) 3571-3578.
- 15 Felicio LS, Nelson JF, Finch CE. Longitudinal studies of estrous cyclicity in aging C57BL/6J mice: Cessation of cyclicity and the duration of persistent vaginal cornification. Biol Reprod 1984; 31 (03) 446-453.
- 16 Finch CE, Felicio LS, Mobbs CV. et al. Ovarian and steroidal influences on neuroendocrine aging processes in female rodents. Endocr Rev 1984; 05 (04) 467-497.
- 17 Finch CE, Jonec V, Wisner Jr JR. et al. Hormone production by the pituitary and testes of male C57BL/6J mice during aging. Endocrinology 1977; 101 (04) 1310-1317.
- 18 Franken PR, Guglielmi J, Vanhove C. et al. Distribution and dynamics of 99mTc-pertechnetate uptake in the thyroid and other organs assessed by single-photon emission computed tomography in living mice. Thyroid 2010; 20 (05) 519-526.
- 19 Gee DM, Flurkey K, Finch CE. Aging and the regulation of luteinizing hormone in C57BL/6J mice: impaired elevations after ovariectomy and spontaneous elevations at advanced ages. Biol Reprod 1983; 28 (03) 598-607.
- 20 Gosden RG, Laing SC, Felicio LS. et al. Imminent oocyte exhaustion and reduced follicular recruitment mark the transition to acyclicity in aging C57BL/6J mice. Biol Reprod 1983; 28 (02) 255-260.
- 21 Haus E. Chronobiology in the endocrine system. Adv Drug Deliv Rev 2007; 59 9–10 985-1014.
- 22 Jauregui-Osoro M, Sunassee K, Weeks AJ. et al. Synthesis and biological evaluation of [18F]tetrafluoroborate: a PET imaging agent for thyroid disease and reporter gene imaging of the sodium/iodide symporter. Eur J Nucl Med Mol Imaging 2010; 37 (11) 2108-2116.
- 23 Josefsson M, Grunditz T, Ohlsson T. et al. Sodium/ iodide-symporter: distribution in different mammals and role in entero-thyroid circulation of iodide. Acta Physiol Scand 2002; 175 (02) 129-137.
- 24 Khalil MM, Tremoleda JL, Bayomy TB. et al. Molecular SPECT Imaging: An Overview. Int J Mol Imaging 2011; 2011: 796025.
- 25 Koba W, Jelicks LA, Fine EJ. MicroPET/SPECT/ CT imaging of small animal models of disease. Am J Pathol 2013; 182 (02) 319-324.
- 26 Lange C, Apostolova I, Lukas M. et al. Performance evaluation of stationary and semi-stationary acquisition with a non-stationary small animal multi-pinhole SPECT system. Mol Imaging Biol 2014; 16 (03) 311-316.
- 27 Lima LP, Barros IA, Lisboa PC. et al. Estrogen effects on thyroid iodide uptake and thyroperoxidase activity in normal and ovariectomized rats. Steroids 2006; 71 (08) 653-659.
- 28 Magota K, Kubo N, Kuge Y. et al. Performance characterization of the Inveon preclinical small-animal PET/SPECT/CT system for multimodality imaging. Eur J Nucl Med Mol Imaging 2011; 38 (04) 742-752.
- 29 Mancini M, Vergara E, Salvatore G. et al. Morphological ultrasound microimaging of thyroid in living mice. Endocrinology 2009; 150 (10) 4810-4815.
- 30 Marti-Climent JM, Collantes M, Jauregui-Osoro M. et al. Radiation dosimetry and biodistribution in non-human primates of the sodium/iodide PET ligand [18F]-tetrafluoroborate. EJNMMI Res 2015; 05 (01) 70.
- 31 Meikle SR, Kench P, Kassiou M. et al. Small animal SPECT and its place in the matrix of molecular imaging technologies. Phys Med Biol 2005; 50 (22) R45-61.
- 32 Morris CJ, Aeschbach D, Scheer FA. Circadian system, sleep and endocrinology. Mol Cell Endocrinol 2012; 349 (01) 91-104.
- 33 Nelson JF, Felicio LS, Randall PK. et al. A longitudinal study of estrous cyclicity in aging C57BL/6J mice: I. Cycle frequency, length and vaginal cytology. Biol Reprod 1982; 27 (02) 327-339.
- 34 O’Doherty J, Jauregui-Osoro M, Brothwood T. et al. 18F-Tetrafluoroborate, a PET Probe for Imaging Sodium/Iodide Symporter Expression: Whole-Body Biodistribution, Safety, and Radiation Dosimetry in Thyroid Cancer Patients. J Nucl Med 2017; 58 (10) 1666-1671.
- 35 Ramos CD, Zantut Wittmann DE, Etchebehere EC. et al. Thyroid uptake and scintigraphy using 99mTc pertechnetate: standardization in normal individuals. Sao Paulo Med J 2002; 120 (02) 45-48.
- 36 Rowland DJ, Cherry SR. Small-animal preclinical nuclear medicine instrumentation and methodology. Semin Nucl Med 2008; 38 (03) 209-222.
- 37 Schmohl KA, Gupta A, Grunwald GK. et al. Imaging and targeted therapy of pancreatic ductal adenocarcinoma using the theranostic sodium iodide symporter (NIS) gene. Oncotarget 2017; 08 (20) 33393-33404.
- 38 Siegel JA, Harpen MD, Lee WP. et al. Quantitative differences between the thyroid uptake of 123I and 99mTc. Eur J Nucl Med 1984; 09 (11) 494-498.
- 39 Spitzweg C, O’Connor MK, Bergert ER. et al. Treatment of prostate cancer by radioiodine therapy after tissue-specific expression of the sodium iodide symporter. Cancer Res 2000; 60 (22) 6526-6530.
- 40 Steinlechner S. Biological Rhythms of the Mouse. In: Hedrich HJ. The Laboratory Mouse. Elsevier; 2nd Edition. 2012: 383-407.
- 41 Terrovitis J, Kwok KF, Lautamaki R. et al. Ectopic expression of the sodium-iodide symporter enables imaging of transplanted cardiac stem cells in vivo by single-photon emission computed tomography or positron emission tomography. J Am Coll Cardiol 2008; 52 (20) 1652-1660.
- 42 Weinert D, Waterhouse J. Diurnally changing effects of locomotor activity on body temperature in laboratory mice. Physiol Behav 1998; 63 (05) 837-843.
- 43 Wood GA, Fata JE, Watson KL. et al. Circulating hormones and estrous stage predict cellular and stromal remodeling in murine uterus. Reproduction 2007; 133 (05) 1035-1044.
- 44 Zuckier LS, Dohan O, Li Y. et al. Kinetics of perrhenate uptake and comparative biodistribution of perrhenate, pertechnetate, and iodide by NaI symporter-expressing tissues in vivo. J Nucl Med 2004; 45 (03) 500-507.