A Facile Radiolabeling of [18F]FDPA via Spirocyclic Iodonium Ylides: Preliminary PET Imaging Studies in Preclinical Models of Neuroinflammation.

Abstract

A suitable TSPO PET ligand may visualize and quantify neuroinflammation in a living brain. Herein we report a 18F-ligand, [18F]2 ([18F]FDPA), is radiolabeled in high yield and high specific activity based on our spirocyclic iodonium ylide (SCIDY) strategy. [18F]2 demonstrated saturable specific binding to TSPO, substantially elevated brain uptake, and slow washout of bound PET signal in the preclinical models of brain neuroinflammation (cerebral ischemia and Alzheimer's disease).

• Authors: Lu Wang, Ran Cheng, Masayuki Fujinaga, Jian Yang, Yiding Zhang, Akiko Hatori, Katsushi Kumata, Jing Yang, Neil Vasdev, Yunfei Du, Chongzhao Ran, Ming-Rong Zhang, Steven H Liang
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 60 Issue 12 Pg. 5222-5227 (06 22 2017) ISSN: 1520-4804 [Electronic] United States
• PMID: 28530834 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)

Chemical References

• Carrier Proteins
• Contrast Media
• Fluorine Radioisotopes
• N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide
• Onium Compounds
• Pyrazoles
• Pyrimidines
• Receptors, GABA-A
• Tspo protein, rat

Topics

• Animals
• Autoradiography
• Brain (diagnostic imaging, pathology)
• Carrier Proteins (metabolism)
• Chemistry Techniques, Synthetic
• Contrast Media
• Disease Models, Animal
• Encephalitis (diagnostic imaging)
• Fluorine Radioisotopes (chemistry, pharmacokinetics)
• Isotope Labeling (methods)
• Mice, Transgenic
• Onium Compounds (chemistry)
• Positron-Emission Tomography (methods)
• Pyrazoles (chemistry)
• Pyrimidines (chemistry)
• Rats, Sprague-Dawley
• Receptors, GABA-A (metabolism)
• Tissue Distribution