Alternative strategies for the synthesis of [11C]ER176 for PET imaging of neuroinflammation

  • Appl Radiat Isot. 2021 Dec;178:109954. doi: 10.1016/j.apradiso.2021.109954.
Jason C Mixdorf  1 ,  Dhanabalan Murali  2 ,  Yangchun Xin  2 ,  Alexandra H DiFilippo  3 ,  Eduardo Aluicio-Sarduy  4 ,  Todd E Barnhart  4 ,  Jonathan W Engle  5 ,  Paul A Ellison  4 ,  Bradley T Christian  3
Affiliations
  • 1. Departments of Medical Physics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA; Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, WI, USA. Electronic address: [email protected].
  • 2. Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, WI, USA.
  • 3. Departments of Medical Physics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA; Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, WI, USA.
  • 4. Departments of Medical Physics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.
  • 5. Departments of Medical Physics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA; Radiology, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.
PMID: 34607293 DOI: 10.1016/j.apradiso.2021.109954
Abstract

[11C]ER176 is a next generation PET radioligand for imaging 18 kDa translocator protein, a biomarker for neuroinflammation. The goal of this work was to investigate alternative strategies for the radiochemical synthesis, purification, and formulation of [11C]ER176. An optimized tri-solvent high-performance liquid chromatography (HPLC) protocol is described to separate the hydro-de-chlorinated byproduct from [11C]ER176. A newly implemented solid phase extraction work-up efficiently removed HPLC solvent while maintaining chemical purity and overall radiochemical yield and purity. This new HPLC purification and final formulation was completed within 40 min, providing 2.7 ± 0.5 GBq of [11C]ER176 at end of synthesis with 1400 ± 300 GBq/μmol molar activity while meeting all specifications for radiopharmaceutical quality control tests for human research use.

Keywords
11-Carbon; ER176; Neuroinflammation; PET; Radiochemistry; TSPO.
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