Radiosynthesis and First-In-Human PET/MRI Evaluation with Clinical-Grade [18F]FTC-146

  • Bin Shen
  • Jun Hyung Park
  • Trine Hjørnevik
  • Peter W. Cipriano
  • Daehyun Yoon
  • Praveen K. Gulaka
  • Dawn Holly
  • Deepak Behera
  • Bonnie A. Avery
  • Sanjiv S. Gambhir
  • Christopher R. McCurdy
  • Sandip Biswal
  • Frederick T. Chin
Research Article

DOI: 10.1007/s11307-017-1064-z

Cite this article as:
Shen, B., Park, J.H., Hjørnevik, T. et al. Mol Imaging Biol (2017). doi:10.1007/s11307-017-1064-z
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Abstract

Purpose

Sigma-1 receptors (S1Rs) play an important role in many neurological disorders. Simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) with S1R radioligands may provide valuable information for diagnosing and guiding treatment for these diseases. Our previously reported S1R radioligand, [18F]FTC-146, demonstrated high affinity for the S1R (Ki = 0.0025 nM) and excellent selectivity for the S1R over the sigma-2 receptor (S2Rs; Ki = 364 nM) across several species (from mouse to non-human primate). Herein, we report the clinical-grade radiochemistry filed with exploratory Investigational New Drug (eIND) and first-in-human PET/MRI evaluation of [18F]FTC-146.

Procedures

[18F]FTC-146 is prepared via a direct [18F] fluoride nucleophilic radiolabeling reaction and formulated in 0.9 % NaCl containing no more than 10 % ethanol through sterile filtration. Quality control (QC) was performed based on USP 823 before doses were released for clinical use. The safety and whole body biodistribution of [18F]FTC-146 were evaluated using a simultaneous PET/MR scanner in two representative healthy human subjects.

Results

[18F]FTC-146 was synthesized with a radiochemical yield of 3.3 ± 0.7 % and specific radioactivity of 8.3 ± 3.3 Ci/μmol (n = 10, decay corrected to EOB). Both radiochemical and chemical purities were >95 %; the prepared doses were stable for 4 h at ambient temperature. All QC test results met specified clinical criteria. The in vivo PET/MRI investigations showed that [18F]FTC-146 rapidly crossed the blood brain barrier and accumulated in S1R-rich regions of the brain. There were also radioactivity distributed in the peripheral organs, i.e., the lungs, spleen, pancreas, and thyroid. Furthermore, insignificant uptake of [18F]FTC-146 was observed in cortical bone and muscle.

Conclusion

A reliable and automated radiosynthesis for providing routine clinical-grade [18F]FTC-146 for human studies was established in a modified GE TRACERlab FXFN. PET/MRI demonstrated the initial tracer biodistribution in humans, and clinical studies investigating different S1R-related diseases are in progress.

Key words

Radiopharmaceuticals [18F]FTC-146 Automated radiosynthesis Clinical PET/MRI sigma-1 receptor 

Copyright information

© World Molecular Imaging Society 2017

Authors and Affiliations

  • Bin Shen
    • 1
  • Jun Hyung Park
    • 1
  • Trine Hjørnevik
    • 1
    • 2
    • 3
  • Peter W. Cipriano
    • 1
  • Daehyun Yoon
    • 4
  • Praveen K. Gulaka
    • 1
  • Dawn Holly
    • 1
  • Deepak Behera
    • 1
  • Bonnie A. Avery
    • 5
  • Sanjiv S. Gambhir
    • 1
  • Christopher R. McCurdy
    • 6
  • Sandip Biswal
    • 7
  • Frederick T. Chin
    • 1
  1. 1.Molecular Imaging Program at Stanford (MIPS), Departments of Radiology and Bioengineering, Bio-X ProgramStanford University School of MedicineStanfordUSA
  2. 2.Department of Diagnostic PhysicsOslo University HospitalOsloNorway
  3. 3.The Norwegian Medical Cyclotron CentreOsloNorway
  4. 4.Radiological Sciences Laboratory, Department of RadiologyStanford UniversityStanfordUSA
  5. 5.Department of Pharmaceutics, P1-27University of FloridaGainesvilleUSA
  6. 6.Department of Medicinal Chemistry, College of PharmacyUniversity of FloridaGainesvilleUSA
  7. 7.Department of Radiology and Molecular Imaging Program at Stanford (MIPS)Stanford University School of MedicineStanfordUSA