A phase 2, open-label, multi-center study to evaluate the efficacy and safety of 99mTc-TRODAT-1 SPECT to detect Parkinson’s disease

  • Yu Sun
  • Congjin Liu
  • Zhengping Chen
  • Biao Li
  • Zhongwei Lv
  • Jian Wang
  • Jingjing LouEmail author
  • Jie Tang
  • Yuankai Wang
  • Guangming Zhang
  • Xingdang LiuEmail author
Original Article



To assess the efficacy and safety of 99mTc-TRODAT-1 SPECT in diagnosing Parkinson’s disease (PD).


99mTc-TRODAT-1 SPECT imaging was performed in 34 healthy controls and 96 PD patients 2.5 h later after injection. The striatal image was evaluated visually and semi-quantitively. Sensitivity and specificity of 99mTc-TRODAT-1 SPECT were analyzed according to Hoehn and Yahr scale (HYS). Based on HYS, the PD patients were divided into mild (HYS 1–2) and moderate (HYS 3–5) groups. The uptake ratios of striatum (ST) and cerebellum (CB) in contralateral, ipsilateral and bilateral striatum in different groups were calculated and analyzed. The safety was assessed.


The sensitivity and specificity of 99mTc-TRODAT-1 SPECT to discriminate PD patients from healthy subjects were 98.96% and 94.12% and it has perfect agreement with HYS (κ = 0.94, p < 0.001). The sensitivity to diagnose mild and moderate PD was 43.42% and 95% separately. The uptake ratio in PD patients was significantly lower than that in healthy controls (1.37 ± 0.13 vs 1.68 ± 0.18, p < 0.001). And the uptake ratio in contralateral side was markedly reduced in unilateral PD patients as compared with the ipsilateral side (1.50 ± 0.20 vs 1.46 ± 0.21, p < 0.001). The striatal uptakes in affected striatum and bilateral striatum were reduced with increasing disease severity between healthy control versus mild stage versus moderate stage in the affected striatum and bilateral striatum in PD patients. No serious adverse events or death was observed after injecting 99mTc-TRODAT-1.


We demonstrated that 99mTc-TRODAT-1 was a safety radiotracer which can be used in clinic to diagnose PD using SPECT.


Phase 2 clinical trial 99mTc-TRODAT-1 Dopamine transporter Diagnostic efficacy Parkinson’s disease 




Compliance with ethical standards

Conflicts of interest

No potential conflicts of interest were disclosed.


  1. 1.
    Tolosa E, Wenning G, Poewe W. The diagnosis of Parkinson's disease. Lancet Neurol. 2006;5(1):75–86.PubMedGoogle Scholar
  2. 2.
    Marsden CD. Parkinson's disease. Lancet. 1990;335(8695):948–52.PubMedGoogle Scholar
  3. 3.
    Wilson JM, Levey AI, Rajput A, Ang L, Guttman M, Shannak K, et al. Differential changes in neurochemical markers of striatal dopamine nerve terminals in idiopathic Parkinson’s disease. Neurology. 1996;47(3):718–26.PubMedGoogle Scholar
  4. 4.
    Brooks DJ. Molecular imaging of dopamine transporters. Ageing Res Rev. 2016;30:114–21.PubMedGoogle Scholar
  5. 5.
    Berti V, Pupi A, Mosconi L. PET/CT in diagnosis of movement disorders. Ann N Y Acad Sci. 2011;1228(1):93–108.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Hwang WJ, Yao WJ, Wey SP, Ting G. Reproducibility of 99mTc-TRODAT-1 SPECT measurement of dopamine transporters in Parkinson's disease. J Nucl Med. 2004;45(2):207–13.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Kung MP, Stevenson DA, Plossl K, Meegalla SK, Beckwith A, Essman WD, et al. [99mTc]TRODAT-1: a novel technetium-99m complex as a dopamine transporter imaging agent. Eur J Nucl Med. 1997;24(4):372–80.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Meegalla S, Plossl K, Kung MP, Chumpradit S, Stevenson DA, Frederick D, et al. Tc-99m-labeled tropanes as dopamine transporter imaging agents. Bioconjug Chem. 1996;7(4):421–9.PubMedGoogle Scholar
  9. 9.
    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.PubMedGoogle Scholar
  10. 10.
    Chen YK, Liu RS, Huang WS, Wey SP, Ting G, Liu JC, et al. The role of dopamine transporter imaging agent [99mTc]TRODAT-1 in hemi-parkinsonism rat brain. Nucl Med Biol. 2001;28(8):923–8.PubMedGoogle Scholar
  11. 11.
    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.PubMedGoogle Scholar
  12. 12.
    Ma KH, Lee JK, Huang SY, Yeh CB, Shen YC, Shen LH, et al. Simultaneous [99mTc]TRODAT-1 and [123I]ADAM brain SPECT in nonhuman primates. Mol Imaging Biol. 2009;11(4):253–62.PubMedGoogle Scholar
  13. 13.
    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.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Sasannezhad P, Juibary AG, Sadri K, Sadeghi R, Sabour M, Kakhki VRD, et al. (99m)Tc-TRODAT-1 SPECT imaging in early and late onset Parkinson's Disease. Asia Ocean J Nucl Med Biol. 2017;5(2):114–9.PubMedPubMedCentralGoogle Scholar
  15. 15.
    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.PubMedGoogle Scholar
  16. 16.
    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.PubMedGoogle Scholar
  17. 17.
    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.PubMedGoogle Scholar
  18. 18.
    Kung HF, Kung MP, Wey SP, Lin KJ, Yen TC. Clinical acceptance of a molecular imaging agent: a long march with [99mTc]TRODAT. Nucl Med Biol. 2007;34(7):787–9.PubMedGoogle Scholar
  19. 19.
    Lin CC, Fan YM, Lin GY, Yang FC, Cheng CA, Lu KC, et al. 99mTc-TRODAT-1 SPECT as a potential neuroimaging biomarker in patients with restless legs syndrome. Clin Nucl Med. 2016;41(1):e14.PubMedGoogle Scholar
  20. 20.
    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.PubMedGoogle Scholar
  21. 21.
    Chou MC, Lai PH, Li JY. Early white matter injuries associated with dopamine transporter dysfunction in patients with acute CO intoxication: a diffusion kurtosis imaging and Tc-99m TRODAT-1 SPECT study. Eur Radiol. 2019;29(3):1375–83.PubMedGoogle Scholar
  22. 22.
    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.PubMedGoogle Scholar
  23. 23.
    Ping W, Ping H, Dian-Chao Y, Hong L, Jie-Hua X. 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.Google Scholar
  24. 24.
    Bor-Seng-Shu E, Felicio AC, Braga-Neto P, Batista IR, Paiva WS, de Andrade DC, et al. Dopamine transporter imaging using 99mTc-TRODAT-1 SPECT in Parkinson’s disease. Med Sci Monit. 2014;20:1413–8.PubMedPubMedCentralGoogle Scholar
  25. 25.
    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.PubMedGoogle Scholar
  26. 26.
    la Fougere C, Krause J, Krause KH, Josef Gildehaus F, Hacker M, Koch W, et al. Value of 99mTc-TRODAT-1 SPECT to predict clinical response to methylphenidate treatment in adults with attention deficit hyperactivity disorder. Nucl Med Commun. 2006;27(9):733–7.PubMedGoogle Scholar
  27. 27.
    Kish SJ, Shannak K, Hornykiewicz O. Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson’s disease. Pathophysiologic and clinical implications. N Engl J Med 1988;318(14):876–880PubMedGoogle Scholar
  28. 28.
    Huang WS, Ma KH, Chou YH, Chen CY, Liu RS, Liu JC. 99mTc-TRODAT-1 SPECT in healthy and 6-OHDA lesioned parkinsonian monkeys: comparison with 18F-FDOPA PET. Nucl Med Commun. 2003;24(1):77–83.PubMedGoogle Scholar
  29. 29.
    Shyu WC, Lin SZ, Chiang MF, Pang CY, Chen SY, Hsin YL, et al. Early-onset Parkinson’s disease in a Chinese population: 99mTc-TRODAT-1 SPECT, Parkin gene analysis and clinical study. Parkinsonism Relat Disord. 2005;11(3):173–80.PubMedGoogle Scholar
  30. 30.
    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.PubMedGoogle Scholar
  31. 31.
    Mittal BR, Sood A, Shukla J, Vatsa R, Bhusari P, Shree R, et al. 99mTc-TRODAT-1 SPECT/CT imaging as a complementary biomarker in the diagnosis of parkinsonian syndromes. Nucl Med Commun. 2018;39(4):312–8.PubMedGoogle Scholar
  32. 32.
    Patel A, Simon S, Elangoven IM, Amalchandran J, Amalchandran SJ, Jain ST. Dopamine Transporter maging with Tc-99m TRODAT-1 SPECT in Parkinson’s isease and its orrelation with linical isease everity. Asia Ocean J Nucl Med Biol 2019;7(1):22–28Google Scholar
  33. 33.
    Shinto AS, Antony J, Kamaleshwaran K, Vijayan K, Selvan A, Korde A, et al. Correlative 99mTc-labeled tropane derivative single photon emission computer tomography and clinical assessment in the staging of Parkinson disease. World J Nucl Med. 2014;13(3):178–83.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Wooten GF. Are men at greater risk for Parkinson's disease than women? J Neurol Neurosurg Psychiatry. 2004;75(4):637–9.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Taylor KS, Cook JA, Counsell CE. Heterogeneity in male to female risk for Parkinson's disease. J Neurol Neurosurg Psychiatry. 2007;78(8):905–6.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Moisan F, Kab S, Mohamed F, Canonico M, Le Guern M, Quintin C, et al. Parkinson disease male-to-female ratios increase with age: French nationwide study and meta-analysis. J Neurol Neurosurg Psychiatry. 2016;87(9):952–7.PubMedGoogle Scholar
  37. 37.
    Picillo M, Nicoletti A, Fetoni V, Garavaglia B, Barone P, Pellecchia MT. The relevance of gender in Parkinson's disease: a review. J Neurol. 2017;264(8):1583–607.PubMedGoogle Scholar
  38. 38.
    Tanner CM, Goldman SM. Epidemiology of Parkinson's disease. Neurol Clin. 1996;14(2):317–35.PubMedGoogle Scholar
  39. 39.
    Inestrosa NC, Marzolo MP, Bonnefont AB. Cellular and molecular basis of estrogen's neuroprotection. Potential relevance for Alzheimer's disease. Mol Neurobiol 1998;17 (1–3):73–86PubMedGoogle Scholar
  40. 40.
    Pankratz N, Nichols WC, Uniacke SK, Halter C, Rudolph A, Shults C, et al. Genome screen to identify susceptibility genes for Parkinson disease in a sample without parkin mutations. Am J Hum Genet. 2002;71(1):124–35.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Oostra RJ, Kemp S, Bolhuis PA, Bleeker-Wagemakers EM. No evidence for 'skewed' inactivation of the X-chromosome as cause of Leber's hereditary optic neuropathy in female carriers. Hum Genet. 1996;97(4):500–5.PubMedGoogle Scholar
  42. 42.
    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.PubMedGoogle Scholar

Copyright information

© The Japanese Society of Nuclear Medicine 2019

Authors and Affiliations

  • Yu Sun
    • 1
  • Congjin Liu
    • 1
  • Zhengping Chen
    • 2
  • Biao Li
    • 3
  • Zhongwei Lv
    • 4
  • Jian Wang
    • 5
  • Jingjing Lou
    • 6
    Email author
  • Jie Tang
    • 2
  • Yuankai Wang
    • 1
  • Guangming Zhang
    • 1
  • Xingdang Liu
    • 1
    Email author
  1. 1.Department of Nuclear Medicine, Huashan HospitalFudan UniversityShanghaiChina
  2. 2.Key Laboratory of Nuclear Medicine, Ministry of HealthJiangsu Key Laboratory of Molecular Nuclear MedicineWuxiChina
  3. 3.Department of Nuclear Medicine, Ruijin HospitalShanghai Jiaotong UniversityShanghaiChina
  4. 4.Department of Nuclear Medicine, Shanghai Tenth People’s HospitalTongji University School of MedicineShanghaiChina
  5. 5.Department of Neurology and National Clinical Research Center for Aging and Medicine, Huashan HospitalFudan UniversityShanghaiChina
  6. 6.Universal Medical Imaging Diagnostic CenterShanghaiChina

Personalised recommendations