HANK & LIN'S GROUP

The past is prologue and the future is scintillating

[18F]F-D6-FP-DTBZ ---------

A next-generation VMAT2 imaging agent 

[18F]-D6-FP-DTBZ

(18F-P17-059，18F-D6-AV133):

A new VMAT2 imaging agent for PD

(IND # 138682)

  1. EJNMMI radiopharm. chem.9, 71 (2024). https://doi.org/10.1186/s41181-024-00301-y

  2. Journal of Nuclear Medicine. June 2024,65(supplement 2)241196

  3. Journal of Nuclear Medicine May 2019, 60 (supplement 1) 1617

  4. Journal of Nuclear Medicine 59.supplement 1 (2018): 1030

  5. Journal of Chromatography B 1121 (2019): 28-38

  6. Nuclear medicine and biology 72 (2019): 26-35

  7. Nuclear medicine and biology 57 (2018): 42-49.

Introduction to [18F]F-D6-FP-DTBZ：

A promising next-generation PET imaging agent for neurodegenerative diseases.

  • Chemical Structure and Mechanism:

[18F]F-D6-FP-DTBZ, also known as [18F]fluoropropyl-dihydrotetrabenazine, is a radiolabeled analog of dihydrotetrabenazine (DTBZ). It selectively binds to VMAT2, which is responsible for packaging monoamines like dopamine into synaptic vesicles. The incorporation of fluorine-18 ([18F]) allows for high-resolution PET imaging, providing detailed insights into VMAT2 density and distribution in the brain and pancreas.

  • Conclusion:

[18F]F-D6-FP-DTBZ is a versatile, innovative PET imaging agent with broad applications in neurodegeneration and metabolic disorders. Its development highlights the increasing role of molecular imaging in precision medicine, offering new opportunities for early diagnosis, treatment monitoring, and therapeutic development. Future research will focus on expanding clinical applications, refining imaging protocols, and optimizing tracer production for wider clinical use.

[18F]D6-FP-DTBZ Vs [18F]AV-133 Publications:

  1. Liu, F., et al. "Deuterated 18F-9-O-hexadeutero-3-fluoropropoxyl-(+)-dihydrotetrabenazine (D6-FP-(+)-DTBZ): A vesicular monoamine transporter 2 (VMAT2) imaging agent." Nuclear medicine and biology 57 (2018): 42-49. https://doi.org/10.1016/j.nucmedbio.2017.11.009
  2. Zhao, R., et al. "VMAT2 imaging agent, D6-[18F] FP-(+)-DTBZ: Improved radiosynthesis, purification by solid-phase extraction and characterization." Nuclear medicine and biology 72 (2019): 26-35. https://doi.org/10.1016/j.nucmedbio.2019.07.002
  3. Sun, M., et al. "Rapid screening of nine unradiolabeled candidate compounds as PET brain imaging agents using cassette-wave microdosing and LC-MS/MS." Journal of Chromatography B 1121 (2019): 28-38. https://doi.org/10.1016/j.jchromb.2019.05.006
  4. Ploessl, K., et al. "x Deuterium substituted D6FPDTBZ (P17-059) as a new VMAT2 imaging agent." Journal of Nuclear Medicine 59.supplement 1 (2018): 1030-1030.
  5. Kilbourn, M. "PET Imaging of Vesicular Monoamine Transporters." PET and SPECT of Neurobiological Systems. Springer, Cham, 2021. 1091-1132.
  6. Zhu, L., et al. "An improved radiosynthesis of [18F] AV-133: a PET imaging agent for vesicular monoamine transporter 2." Nuclear medicine and biology 37.2 (2010): 133-141. https://doi.org/10.1016/j.nucmedbio.2009.10.005
  7. Xiao, H., et al. "Developing a cassette microdosing approach to enhance the throughput of PET imaging agent screening." Journal of pharmaceutical and biomedical analysis 154 (2018): 48-56. https://doi.org/10.1016/j.jpba.2018.02.063
  8. Zhu, L., et al. "A comparative dynamic PET imaging of monkey brains between solid phase extraction and HPLC purified 18F AV-133." Journal of Nuclear Medicine 51.supplement 2 (2010): 584-584.
  9. Zhu, L., et al. "Imaging of VMAT2 binding sites in the brain by 18F-AV-133: The effect of a pseudo-carrier." Nuclear medicine and biology 39.7 (2012): 897-904. https://doi.org/10.1016/j.nucmedbio.2012.05.002
  10. Ruiyue Zhao, Zhihao Zha, Karl Ploessl, Seok Choi, Futao Liu, Lin Zhu and Hank Kung. Improved preparation of D6-[18F]FP-(+)-DTBZ: A new vesicular monoamine transporter 2 (VMAT2) imaging agent.Journal of Nuclear Medicine May 2019, 60 (supplement 1) 1617

  11. Zhao R, Zhang Y, Xu S, Alexoff D, Ploessl K, Chen L, Kung HF, Zhu L, Wang X. First-in-human study of D6-[18F] FP-(+)-DTBZ, a novel VMAT2 tracer: whole-body biodistribution and brain PET comparison with [18F] FP-(+)-DTBZ (AV-133). Journal of Nuclear Medicine. June 2024,65(supplement 2)241196

  12. Zhao, R., Chen, J., Ye, T.et al.First-in-human study of D6-[18F]FP-(+)-DTBZ, a novel VMAT2 tracer: whole-body biodistribution and brain PET comparison with [18F]FP-(+)-DTBZ (AV-133).EJNMMI radiopharm. chem.9, 71 (2024).

    https://doi.org/10.1186/s41181-024-00301-y

Zhao, R., Chen, J., Ye, T.et al.First-in-human study of D6-[18F]FP-(+)-DTBZ, a novel VMAT2 tracer: whole-body biodistribution and brain PET comparison with [18F]FP-(+)-DTBZ (AV-133).

EJNMMI radiopharm. chem.9, 71 (2024). https://doi.org/10.1186/s41181-024-00301-y

18F-D6-FP-DTBZ (D6-AV133) PET imaging for PD （图片来自广州医科大学附属第一医院核医学科）
 

VMAT2显像剂：美国FDA批准临床研究（I-II期）

VMAT2显像剂：美国FDA批准临床研究（I-II期）

VMAT2显像剂：美国FDA批准临床研究（I-II期）

Journal of Nuclear Medicine. June 2024,65(supplement 2)241196