» Articles » PMID: 34363068

Translation of C-labeled Tracer Synthesis to a CGMP Environment As Exemplified by [C]ER176 for PET Imaging of Human TSPO

Overview
Journal Nat Protoc
Specialties Biology
Pathology
Science
Date 2021 Aug 7
PMID 34363068
Citations 4
Authors
Affiliations
Soon will be listed here.
Abstract

Radiotracers labeled with carbon-11 (t = 20.4 min) are widely used with positron emission tomography for biomedical research. Radiotracers must be produced for positron emission tomography studies in humans according to prescribed time schedules while also meeting current good manufacturing practice. Translation of an experimental radiosynthesis to a current good manufacturing practice environment is challenging. Here we exemplify such translation with a protocol for the production of an emerging radiotracer for imaging brain translocator protein 18 kDa, namely [C]ER176. This radiotracer is produced by rapid conversion of cyclotron-produced [C]carbon dioxide into [C]iodomethane, which is then used to treat N-desmethyl-ER176 in the presence of base (BuOK) at room temperature for 5 min. [C]ER176 is separated in high purity by reversed-phase HPLC and formulated for intravenous injection in sterile ethanol-saline. The radiosynthesis is reliable and takes 50 min. Quality control takes another 20 min. All aspects of the protocol, including quality control, are discussed.

Citing Articles

Radiopharmaceuticals and their applications in medicine.

Zhang S, Wang X, Gao X, Chen X, Li L, Li G Signal Transduct Target Ther. 2025; 10(1):1.

PMID: 39747850 PMC: 11697352. DOI: 10.1038/s41392-024-02041-6.


Essential Principles and Recent Progress in the Development of TSPO PET Ligands for Neuroinflammation Imaging.

Viviano M, Barresi E, Simeon F, Costa B, Taliani S, Da Settimo F Curr Med Chem. 2022; 29(28):4862-4890.

PMID: 35352645 PMC: 10080361. DOI: 10.2174/0929867329666220329204054.


Synthesis and Screening in Mice of Fluorine-Containing PET Radioligands for TSPO: Discovery of a Promising F-Labeled Ligand.

Simeon F, Lee J, Morse C, Stukes I, Zoghbi S, Manly L J Med Chem. 2021; 64(22):16731-16745.

PMID: 34756026 PMC: 8817670. DOI: 10.1021/acs.jmedchem.1c01562.


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

Mixdorf J, Murali D, Xin Y, DiFilippo A, Aluicio-Sarduy E, Barnhart T Appl Radiat Isot. 2021; 178:109954.

PMID: 34607293 PMC: 9191690. DOI: 10.1016/j.apradiso.2021.109954.

References
1.
Ametamey S, Honer M, Schubiger P . Molecular imaging with PET. Chem Rev. 2008; 108(5):1501-16. DOI: 10.1021/cr0782426. View

2.
Phelps M . Positron emission tomography provides molecular imaging of biological processes. Proc Natl Acad Sci U S A. 2000; 97(16):9226-33. PMC: 16850. DOI: 10.1073/pnas.97.16.9226. View

3.
Zanotti-Fregonara P, Zhang Y, Jenko K, Gladding R, Zoghbi S, Fujita M . Synthesis and evaluation of translocator 18 kDa protein (TSPO) positron emission tomography (PET) radioligands with low binding sensitivity to human single nucleotide polymorphism rs6971. ACS Chem Neurosci. 2014; 5(10):963-71. PMC: 4210126. DOI: 10.1021/cn500138n. View

4.
Fan J, Lindemann P, Feuilloley M, Papadopoulos V . Structural and functional evolution of the translocator protein (18 kDa). Curr Mol Med. 2012; 12(4):369-86. DOI: 10.2174/1566524011207040369. View

5.
Jaremko L, Jaremko M, Giller K, Becker S, Zweckstetter M . Structure of the mitochondrial translocator protein in complex with a diagnostic ligand. Science. 2014; 343(6177):1363-6. PMC: 5650047. DOI: 10.1126/science.1248725. View