Abstract
Objectives
To study the pharmacokinetics, biodistribution, and injection doses of 99mTc-TRODAT-1 in healthy adults.
Methods
Thirty healthy individuals comprising 15 females and 15 males were randomly divided into three groups and the injection doses of 99mTc-TRODAT-1 of group 1, 2, and 3 were 370 MBq, 740 MBq, and 1110 MBq, respectively. Assessments of subjective symptoms and tests were performed before and after injection. Blood and urine collections and whole-body planar imaging were analyzed at various time points. Bilateral brain striatal SPECT images obtained at 3.5 h PI were assessed visually and semiquantitatively.
Results
No serious adverse events or deaths were observed in our study. The pharmacokinetic analysis showed that 99mTc-TRODAT-1 was eliminated rapidly from the circulation, with just about 4% of the injected dose remaining in blood at 1 h post-injection. The mean cumulative urinary excretion over 24 h was just 2.96 ± 0.96%ID. The time-activity curve demonstrated that the radioactivity was mainly in liver and abdomen. The highest absorbed dose was in the dose-limiting organ, liver (20.88 ± 4.45 × 10−3 mSv/MBq). The average effective dose was 5.22 ± 1.05 × 10−3 mSv/MBq. The clarity of striatal images assessed visually in group 1 was worse than that in group 2 and 3. The semiquantitative analysis showed that there were no differences in striatum/cerebellum between the three groups (group 1: 1.77 ± 0.11, group 2: 1.62 ± 0.14, and group 3: 1.75 ± 0.20; P = 0.088).
Conclusions
99mTc-TRODAT-1 was safe to use in humans and showed the status of dopaminergic neurons specifically and clearly. The injection dose we suggested was 740 MBq.
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References
Kalia LV, Lang AE. Parkinson’s disease. The Lancet. 2015;386(9996):896–912.
Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992;55(3):181–4.
Chen N, Reith ME. Structure and function of the dopamine transporter. Eur J Pharmacol. 2000;405(1–3):329–39.
Mozley PD, Schneider JS, Acton PD, Plossl K, Stern MB, Siderowf A, et al. Binding of [99mTc]TRODAT-1 to dopamine transporters in patients with Parkinson’s disease and in healthy volunteers. J Nucl Med. 2000;41(4):584–9.
Staffen W, Mair A, Unterrainer J, Trinka E, Ladurner G. Measuring the progression of idiopathic Parkinson’s disease with [123I] beta-CIT SPECT. J Neural Transm (Vienna). 2000;107(5):543–52.
Wang J, Zuo CT, Jiang YP, Guan YH, Chen ZP, Xiang JD, et al. 18F-FP-CIT PET imaging and SPM analysis of dopamine transporters in Parkinson’s disease in various Hoehn & Yahr stages. J Neurol. 2007;254(2):185–90.
Kung HF, Kim HJ, Kung MP, Meegalla SK, Plossl K, Lee HK. Imaging of dopamine transporters in humans with technetium-99m TRODAT-1. Eur J Nucl Med. 1996;23(11):1527–30.
Chou KL, Hurtig HI, Stern MB, Colcher A, Ravina B, Newberg A, et al. Diagnostic accuracy of [99mTc]TRODAT-1 SPECT imaging in early Parkinson’s disease. Parkinsonism Relat Disord. 2004;10(6):375–9.
Huang WS, Lin SZ, Lin JC, Wey SP, Ting G, Liu RS. Evaluation of early-stage Parkinson’s disease with 99mTc-TRODAT-1 imaging. J Nucl Med. 2001;42(9):1303–8.
Tzen KY, Lu CS, Yen TC, Wey SP, Ting G. Differential diagnosis of Parkinson’s disease and vascular parkinsonism by (99m)Tc-TRODAT-1. J Nucl Med. 2001;42(3):408–13.
Sun Y, Liu CJ, Zp Chen, Li B, Lv ZW, Lou JJ, et al. A phase 2, open-label, multi-center study to evaluate the efficacy and safety of Tc-TRODAT-1 SPECT to detect Parkinson’s disease. Ann Nucl Med. 2019. https://doi.org/10.1007/s12149-019-01412-2.
Fallahi B, Esmaeili A, Beiki D, Oveisgharan S, Noorollahi-Moghaddam H, Erfani M, et al. Evaluation of (99m)Tc-TRODAT-1 SPECT in the diagnosis of Parkinson’s disease versus other progressive movement disorders. Ann Nucl Med. 2016;30(2):153–62.
Wang J, Jiang YP, Liu XD, Chen ZP, Yang LQ, Liu CJ, et al. 99mTc-TRODAT-1 SPECT study in early Parkinson’s disease and essential tremor. Acta Neurol Scand. 2005;112(6):380–5.
Fang P, Wu CY, Liu ZG, Wan WX, Wang TS, Chen SD, et al. The preclinical pharmacologic study of dopamine transporter imaging agent [99mTc]TRODAT-1. Nucl Med Biol. 2000;27(1):69–75.
Mozley PD, Stubbs JB, Plossl K, Dresel SH, Barraclough ED, Alavi A, et al. Biodistribution and dosimetry of TRODAT-1: a technetium-99m tropane for imaging dopamine transporters. J Nucl Med. 1998;39(12):2069–76.
Meegalla SK, Plossl K, Kung MP, Chumpradit S, Stevenson DA, Kushner SA, et al. Synthesis and characterization of technetium-99m-labeled tropanes as dopamine transporter-imaging agents. J Med Chem. 1997;40(1):9–17.
Dresel SH, Kung MP, Huang X, Plossl K, Hou C, Shiue CY, et al. In vivo imaging of serotonin transporters with [99mTc]TRODAT-1 in nonhuman primates. Eur J Nucl Med. 1999;26(4):342–7.
Hu P, Chen L, Zhang HQ, Li JR, Liang H. Single photon emission computer tomography of dopamine transporters in monkeys and humans with 99mTc-TRODAT-1. Chin Med J Engl. 2004;117(7):1056–9.
Hwang JJ, Liao MH, Yen TC, Wey SP, Lin KJ, Pan WH, et al. Biodistribution study of [99mTc] TRODAT-1 alone or combined with other dopaminergic drugs in mice with macroautoradiography. Appl Radiat Isot. 2002;57(1):35–42.
Weng YH, Yen TC, Chen MC, Kao PF, Tzen KY, Chen RS, et al. Sensitivity and specificity of 99mTc-TRODAT-1 SPECT imaging in differentiating patients with idiopathic Parkinson’s disease from healthy subjects. J Nucl Med. 2004;45(3):393–401.
Koch W, Pogarell O, Popperl G, Hornung J, Hamann C, Gildehaus FJ, et al. Extended studies of the striatal uptake of 99mTc-NC100697 in healthy volunteers. J Nucl Med. 2007;48(1):27–34.
Kushner SA, McElgin WT, Kung MP, Mozley PD, Plossl K, Meegalla SK, et al. Kinetic modeling of [99mTc]TRODAT-1: a dopamine transporter imaging agent. J Nucl Med. 1999;40(1):150–8.
Cleynhens BJ, de Groot TJ, Vanbilloen HP, Kieffer D, Mortelmans L, Bormans GM, et al. Technetium-99m labelled integrated tropane-BAT as a potential dopamine transporter tracer. Bioorg Med Chem. 2005;13(4):1053–8.
Huang CK, Wu J, Cheng KY, Pan LK. Optimization of imaging parameters for SPECT scans of [99mTc]TRODAT-1 using Taguchi analysis. PLoS ONE. 2015;10(3):e0113817.
Bao SY, Wu JC, Luo WF, Fang P, Liu ZL, Tang J. Imaging of dopamine transporters with technetium-99m TRODAT-1 and single photon emission computed tomography. J Neuroimaging. 2000;10(4):200–3.
Wang P, Hu P, Yue DC, Liang H, Xu JH. The clinical value of Tc-99m TRODAT-1 SPECT for evaluating disease severity in young patients with symptomatic and asymptomatic Wilson disease. Clin Nucl Med. 2007;32(11):844–9.
Varrone A, Dickson JC, Tossici-Bolt L, Sera T, Asenbaum S, Booij J, et al. European multicentre database of healthy controls for [123I]FP-CIT SPECT (ENC-DAT): age-related effects, gender differences and evaluation of different methods of analysis. Eur J Nucl Med Mol Imaging. 2013;40(2):213–27.
Mozley PD, Acton PD, Barraclough ED, Plossl K, Gur RC, Alavi A, et al. Effects of age on dopamine transporters in healthy humans. J Nucl Med. 1999;40(11):1812–7.
Volkow ND, Fowler JS, Wang GJ, Logan J, Schlyer D, MacGregor R, et al. Decreased dopamine transporters with age in health human subjects. Ann Neurol. 1994;36(2):237–9.
van Dyck CH, Seibyl JP, Malison RT, Laruelle M, Zoghbi SS, Baldwin RM, et al. Age-related decline in dopamine transporters: analysis of striatal subregions, nonlinear effects, and hemispheric asymmetries. Am J Geriatr Psychiatry. 2002;10(1):36–43.
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Sun, Y., Chen, Z., Liu, C. et al. Phase I clinical study with different doses of 99mTc-TRODAT-1 in healthy adults. Ann Nucl Med 34, 212–219 (2020). https://doi.org/10.1007/s12149-020-01444-z
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DOI: https://doi.org/10.1007/s12149-020-01444-z