Semi-automatic synthesis and biodistribution of N-(2-18F-fluoropropionyl)-bis(zinc (II)-dipicolylamine) (18F-FP-DPAZn2) for AD model imaging

BMC Med Imaging. 2017 Apr 21;17(1):27. doi: 10.1186/s12880-017-0200-1.

Abstract

Background: Phosphatidylserine (PS)-targeting positron emission tomography (PET) imaging with labeled small-molecule tracer is a crucial non-invasive molecule imaging method of apoptosis. In this study, semi-automatic radiosynthesis and biodistribution of N-(2-18F-fluoropropionyl)-bis(zinc(II)-dipicolylamine) (18F-FP-DPAZn2), as a potential small-molecule tracer for PET imaging of cell death in Alzheimer's disease (AD) model, were performed.

Methods: 18F-FP-DPAZn2 was synthesized on the modified PET-MF-2V-IT-I synthesizer. Biodistribution was determined in normal mice and PET images of AD model were obtained on a micro PET-CT scanner.

Results: With the modified synthesizer, the total decay-corrected radiochemical yield of 18F-FP-DPAZn2 was 35 ± 6% (n = 5) from 18F- within 105 ± 10 min. Biodistribution results showed that kidney has the highest uptake of 18F-FP-DPAZn2. The uptake of radioactivity in brain kept at a relatively low level during the whole observed time. In vivo 18F-FP-DPAZn2 PET images demonstrated more accumulation of radioactivity in the brain of AD model mice than that in the brain of normal mice.

Conclusions: The semi-automatic synthetic method provides a slightly higher radiochemical yield and shorter whole synthesis time of 18F-FP-DPAZn2 than the manual operation method. This improved method can give enough radioactivity and high radiochemical purity of 18F-FP-DPAZn2 for in vivo PET imaging. The results show that 18F-FP-DPAZn2 seems to be a potential cell death tracer for AD imaging.

Keywords: 18F-FP-DPAZn2; 18F-NFP; Cell death; Semi-automatic synthesis; Zinc(II)-dipicolylamine.

MeSH terms

  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / metabolism*
  • Animals
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Drug Compounding / methods
  • Fluorine Radioisotopes / chemistry
  • Fluorine Radioisotopes / pharmacokinetics*
  • Isotope Labeling / methods*
  • Metabolic Clearance Rate
  • Mice
  • Molecular Imaging / methods
  • Organ Specificity
  • Organometallic Compounds / chemical synthesis*
  • Organometallic Compounds / pharmacokinetics*
  • Picolinic Acids / chemical synthesis*
  • Picolinic Acids / pharmacokinetics*
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics
  • Robotics / methods
  • Tissue Distribution

Substances

  • Fluorine Radioisotopes
  • Organometallic Compounds
  • Picolinic Acids
  • Radiopharmaceuticals
  • bis-dipicolylamine-Zinc(II)
  • Fluorine-18