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

Jason C Mixdorf; Dhanabalan Murali; Yangchun Xin; Alexandra H DiFilippo; Eduardo Aluicio-Sarduy; Todd E Barnhart; Jonathan W Engle; Paul A Ellison; Bradley T Christian

doi:10.1016/j.apradiso.2021.109954

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. Epub 2021 Sep 17.

Authors

Jason C Mixdorf¹, Dhanabalan Murali², Yangchun Xin², Alexandra H DiFilippo³, Eduardo Aluicio-Sarduy⁴, Todd E Barnhart⁴, Jonathan W Engle⁵, Paul A Ellison⁴, Bradley T Christian³

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: jmixdorf@wisc.edu.
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.

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.

MeSH terms

Carbon Radioisotopes / chemistry*
Chromatography, High Pressure Liquid
Humans
Neuroinflammatory Diseases / diagnostic imaging*
Positron-Emission Tomography / methods*
Quality Control
Radiopharmaceuticals / administration & dosage
Radiopharmaceuticals / chemical synthesis*
Solid Phase Extraction
Spectrophotometry, Ultraviolet

Substances

Carbon Radioisotopes
Carbon-11
Radiopharmaceuticals

Grants and funding

T32 CA009206/CA/NCI NIH HHS/United States