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The Titrated Mannitol Improved Central [[sup.99m]Tc] Tc TRODAT-1 Uptake in an Animal Model—A Clinically Feasible Application

International journal of molecular sciences, 2023-02, Vol.24 (4) [Peer Reviewed Journal]

COPYRIGHT 2023 MDPI AG ;ISSN: 1422-0067 ;EISSN: 1422-0067 ;DOI: 10.3390/ijms24043773

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  • Title:
    The Titrated Mannitol Improved Central [[sup.99m]Tc] Tc TRODAT-1 Uptake in an Animal Model—A Clinically Feasible Application
  • Author: Chang, Kang-Wei ; Chang, Po-Ling ; Tsai, Chi-Jung ; Tsai, Ya-Ju ; Wu, Ping-Hsiu ; Lee, Hsin-Lun ; Lai, Yu-Hua ; Wong, Ching-Yee Oliver ; Huang, Wen-Sheng
  • Subjects: Mannitol ; Medical research ; Medicine, Experimental ; Neurons
  • Is Part Of: International journal of molecular sciences, 2023-02, Vol.24 (4)
  • Description: [[sup.99m]Tc]Tc TRODAT-1 is a widely used single photon emission tomography (SPECT) radiopharmaceutical in Asian practice for early detection of central dopaminergic disorders. However, its imaging quality remains sub-optimal. To overcome this problem, mannitol, an osmotic agent was used to observe its effect on improving striatal [[sup.99m]Tc]Tc TRODAT-1 uptake in rat brain by titrated human dosages to investigate a clinically feasible way to improve human imaging quality. [[sup.99m]Tc]Tc TRODAT-1 synthesis and quality control were performed as described. Sprague-Dawley rats were used for this study. The animal in vivo nanoSPECT/CT and ex vivo autoradiography were employed to observe and verify the striatal [[sup.99m]Tc]Tc TRODAT-1 uptake in rat brains using clinically equivalent doses (i.e., 0, 1 and 2 mL groups, each n = 5) of mannitol (20% w/v, equivalent to 200 mg/mL) by an intravenous administration. Specific binding ratios (SBRs) were calculated to express the central striatal uptake in different experimental groups. In the NanoSPECT/CT imaging, the highest SBRs of striatal [[sup.99m]Tc]Tc TRODAT-1 were reached at 75-90 min post-injection. The averaged striatal SBRs were 0.85 ± 0.13 (2 mL normal saline, the control group), 0.94 ± 0.26 (1 mL mannitol group) and 1.36 ± 0.12 (2 mL mannitol group, p < 0.01 which were significantly different than the control as well as 1 mL mannitol groups (p < 0.05). The SBRs from ex vivo autoradiography also showed a comparable trend of the striatal [[sup.99m]Tc]Tc TRODAT-1 uptake in the 2 mL, 1 mL mannitol and the control groups (1.76 ± 0.52, 0.91 ± 0.29, and 0.21 ± 0.03, respectively, p < 0.05). No remarkable changes of vital signs were found in the mannitol groups and the controls. Pre-treated mannitol revealed a significant increase of the central striatal [[sup.99m]Tc]Tc TRODAT-1 uptake in a rat model which not only enabled us to perform pre-clinical studies of dopaminergic related disorders but also provided a potential way to further optimize image quality in clinical practice.
  • Publisher: MDPI AG
  • Language: English
  • Identifier: ISSN: 1422-0067
    EISSN: 1422-0067
    DOI: 10.3390/ijms24043773
  • Source: TestCollectionTL3OpenAccess
    PubMed Central
    ProQuest Central
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