Fully automated synthesis and initial PET evaluation of a TSPO radioligand, [ 11 C]PBR28 (N-(2-[ 11 C]methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide), are reported. These results facilitate the potential preclinical and clinical PET studies of [ 11 C]PBR28 in animals and humans.
Keywords
Translocator protein (TSPO); [ 11 C]PBR28; Radiosynthesis; Positron emission tomography (PET); Traumatic brain injury (TBI); Brain imagingTranslocator protein 18 kDa (TSPO, formerly known as the peripheral benzodiazepine receptor) 1 is a protein found in lung, liver, heart, spleen, kidney, adrenals, brain, glial cells, masts cell and macrophages, and is implicated in numerous nervous system disorders such as epilepsy, cerebral ischemia, nerve injury and neurodegenerative diseases, and immune system diseases such as cancer. 2 Brain TSPO density increases in several neuropathological conditions and after experimental injuries to the central nervous system as well. 3 TSPO is an attractive target for molecular imaging of neuroinflammation like Alzheimer's disease and tumor progression using the biomedical imaging technique positron emission tomography (PET). 4 The prototypical TSPO-selective PET radioligand is [ 11 C]PK11195; however, it is reported to have many limitations such as low brain uptake and low sensitivity. 4 (Qi-Huang Zheng).. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
NIH Public Access
Author ManuscriptBioorg Med Chem Lett. Author manuscript; available in PMC 2010 October 1. The precursor N- (2-hydroxybenzyl)-N-(4-phenoxypyridin-3-yl) NaH was used as a strong base instead of ( t Bu) 4 NOH, and CH 3 CN was used as the reaction solvent instead of MeOH. The reaction temperature 80 °C was higher than room temperature, and the reaction time was only 3 min, shorter than 7 min in the literature. We also used a "vial" method instead of the reported "loop" method. Therefore, the radiochemical yields for [ 11 C]PBR28 in our method is much higher than that reported previously (26%). 11 The radiosynthesis was performed in an in-house automated multi-purpose 11 C-radiosynthesis module, allowing measurement of specific radioactivity during synthesis. 19,20 The overall synthesis, purification and formulation time was 25-30 min from EOB. The specific radioactivity was in a range of 5-15 Ci/μmol at EOB. Chemical purity and radiochemical purity were determined by analytical HPLC. 21 The chemical purity of the precursor and reference standard was > 96%. The radiochemical purity of the target tracer was > 99% determined by radio-HPLC through γ-ray (PIN diode) flow detector, and th...
