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Phase I clinical study with different doses of 99mTc-TRODAT-1 in healthy adults

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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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Author notes

  1. Yu Sun and Zhengping Chen have contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine, Huashan Hospital, Fudan University, No. 12 Wulumuqi Middle Road, Jing’an District, Shanghai, 200040, China

    Yu Sun, Congjin Liu, Yuankai Wang, Guangming Zhang & Xingdang Liu

  2. Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, No. 20 Qianrong Road, Binhu District, Wuxi, 214063, Jiangsu, China

    Zhengping Chen & Jie Tang

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  1. Yu Sun
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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

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