HANK & LIN'S GROUP

The past is prologue and the future is scintillating

[18F]F-D3FSP (18F-P16-129, 18F-D3-AV45) ---------

A new-generation imaging agent with improved sensitivity and selectivity for β-amyloid plaques.

 [18F]F-D3FSP

（18F-P16-129，18F-D3-AV45）：

A new imaging agent of β-amyloid plaques in the brain for diagnosis of Alzheimer's disease (AD)（IND # 137713）

  1. Journal of Nuclear Medicine 60, no. supplement 1 (2019): 1457

  2. European Journal of Nuclear Medicine and Molecular Imaging. 51(2024):2794–2805

  3. Journal of Nuclear MedicineJune 2024,65(supplement 2)(2024): 241105

  4. Alzheimer's & Dementia. 2023 Dec;19:e079352

  5. Alzheimer's & Dementia19 (2023): e077578

  6. 中华核医学与分子影像杂志,2024,44(05)：260-265.

  7. Mol Neurodegeneration 19, 58 (2024)

  8. Alzheimer's Research & Therapy16.1 (2024): 84.

  9. Journal of Nuclear Medicine 59, no. supplement 1 (2018): 1031

  10. Journal of Nuclear Medicine May 2019, 60 (supplement 1) 485

Introduction to [18F]F-D3FSP (18F-P16-129, 18F-D3-AV45)

A next-generation β-amyloid PET imaging agent

  • with improved pharmacokinetics, higher imaging contrast, and better diagnostic performance than its predecessors

1. Chemical Structure and Mechanism：

[18F]F-D3FSP is structurally derived from [18F]Florbetapir, with three deuterium atoms strategically placed to enhance its pharmacokinetics and metabolic stability.

2. Clinical and Research Significance

    With its superior metabolic stability and imaging properties, [18F]F-D3FSP is expected to:

      • Enhance early and accurate AD diagnosis, improving patient stratification.
      • Support longitudinal studies of amyloid progression and treatment response.
      • Facilitate clinical trials of emerging AD therapies, optimizing patient selection.

     Publications：

    1. Wong, Dean, Hiroto Kuwabara, Kelly Kitzmiller, Ayon Nandi, Zabecca Brinson, Noble George, David Alexoff et al. "Comparison of [18F]D3FSP ([18F]P16-129) and [18F]AV45 in Alzheimer’s Disease."Journal of Nuclear Medicine 60, no. supplement 1 (2019): 1457
    2. Li A,et al.[18F]-D3FSP β-amyloid PET imaging in older adults and alzheimer’s disease.European Journal of Nuclear Medicine and Molecular Imaging.51(2024):3990-4000. https://doi.org/10.1007/s00259-024-06835-2
    3. Li, Anqi, Ruiyue Zhao, Mingkai Zhang, Pan Sun, Yue Cai, Lin Zhu, Hank F. Kung, Ying Han, Xinlu Wang, and Tengfei Guo. "[18F]-D3FSP β-amyloid PET Imaging in Alzheimer's Disease."Journal of Nuclear MedicineJune 2024,65(supplement 2) (2024): 241105;
    4. Li A, Zhao R, Zhang M, Sun P, Cai Y, Liu L, Lan G, Zhu Y, Chen X, Guo L, Zhou Y. [18F]-D3FSP amyloid-β PET imaging in elderly adults and Alzheimer’s disease. Alzheimer's & Dementia. 2023 Dec;19:e079352. https://doi.org/10.1002/alz.079352
    5. Guo, Tengfei, et al. "Plasma biomarker and neuroimaging changes in a Chinese community aging cohort: The Greater‐Bay‐Area Healthy Aging Brain Study (GHABS)."Alzheimer's & Dementia19 (2023): e077578. https://doi.org/10.1002/alz.077578
    6. 梁思浩,李安琪,赵睿玥,等. 18F-D3FSP PET/CT在不同程度认知障碍患者中的应用价值 [J]. 中华核医学与分子影像杂志,2024,44(05)：260-265. DOI:10.3760/cma.j.cn321828-20240208-00058
    7. Guo, T., Li, A., Sun, P. et al. Astrocyte reactivity is associated with tau tangle load and cortical thinning in Alzheimer’s disease. Mol Neurodegeneration 19, 58 (2024). https://doi.org/10.1186/s13024-024-00750-8
    8. Shao, Kai, Xiaochen Hu, Luca Kleineidam, Melina Stark, Slawek Altenstein, Holger Amthauer, Henning Boecker et al. "Amyloid and SCD jointly predict cognitive decline across Chinese and German cohorts." Alzheimer's & Dementia (2024). https://doi.org/10.1002/alz.14119
    9. Sun, Pan, et al. "Spatial and temporal patterns of cortical mean diffusivity in Alzheimer's disease and suspected non‐Alzheimer's disease pathophysiology." Alzheimer's & Dementia 2024;20:7048–7061. https://doi.org/10.1002/alz.14176
    10. Liu, Zhen, et al. "Pathophysiology characterization of Alzheimer’s disease in South China’s aging population: for the Greater-Bay-Area Healthy Aging Brain Study (GHABS)."Alzheimer's Research & Therapy16.1 (2024): 84.

      https://doi.org/10.1186/s13195-024-01458-z

    11. Zha Z, Ploessl K, Choi SR, Alexoff D, Kung HF*. Preclinical evaluation of [18F]D3FSP, deuterated AV-45, for imaging of β-amyloid in the brain. Nuclear medicine and biology. 2021 Jan 1;92:97-106. https://doi.org/10.1016/j.nucmedbio.2020.03.003
    12. Zhang L, Zhang A, Yao X, Zhang Y, Liu F, Hong H, Zha Z, Liu Y, Wu Z, Qiao J, Zhu L.“An Improved Preparation of [18F]AV-45 by Simplified Solid-Phase Extraction Purification.” Journal of labelled compounds & radiopharmaceuticals. 63.3 (2020): 108–118.

      https://doi.org/10.1002/jlcr.3813

    13. Yao X, Zha Z, Zhao R, Choi SR, Ploessl K, Liu F, Zhu L, Kung HF. Optimization of solid-phase extraction (SPE) in the preparation of [18F]D3FSP: A new PET imaging agent for mapping Aβ plaques. Nuclear Medicine and Biology. 2019 Apr 1;71:54-64.

      https://doi.org/10.1016/j.nucmedbio.2019.05.002

    14. Zha, Zhihao, Karl Ploessl, David Alexoff, Seok Choi, Zehui Wu, Lin Zhu, and Hank Kung. "[18F]D3FSP ([18F]D3AV-45) as a PET imaging agent for Abeta plaques in the brain." Journal of Nuclear Medicine 59, no. supplement 1 (2018): 1031
    15. Liu Y, Zhu L, Plössl K, Choi SR, Qiao H, Sun X, Li S, Zha Z, Kung HF. "Optimization of automated radiosynthesis of [18F]AV-45: a new PET imaging agent for Alzheimer's disease." Nuclear medicine and biology 37, no. 8 (2010): 917-925.

      https://doi.org/10.1016/j.nucmedbio.2010.05.001

    16. Xiao, Hao, Seok Rye Choi, Ruiyue Zhao, Karl Ploessl, David Alexoff, Lin Zhu, Zhihao Zha, and Hank F. Kung. "A new highly deuterated [18F]AV-45,[18F]D15FSP, for imaging β-Amyloid plaques in the brain." ACS Medicinal Chemistry Letters 12, no. 7 (2021): 1086-1092. https://doi.org/10.1021/acsmedchemlett.1c00062
    17. Xinyue Yao, Ruiyue Zhao, Zhihao Zha, Seok Choi, Karl Ploessl, David Alexoff, Lin Zhu and Hank Kung. Optimization of solid phase extraction (SPE) in preparation of D3-[18F]FSP: A new PET imaging agent for mapping Aβ plaques.Journal of Nuclear Medicine May 2019, 60 (supplement 1) 485
      Dr. Dean Wong, Johns Hopkins University, un-published data, IND #137713, SNMMI abstract 2019

      Dr. Dean Wong, Johns Hopkins University, un-published data, IND #137713, SNMMI abstract 2019

      SNMMI abstract 2024 (Oral)