Synthesis, Radiolabeling, and Biological Evaluation of the trans-Stereoisomers of 1-Amino-3-(fluoro-18F)-4-fluorocyclopentane-1-carboxylic Acid as PET Imaging Agents

Thomas C Pickel; Gouthami Pashikanti; Ronald J Voll; Weiping Yu; Zhaobin Zhang; Jonathon A Nye; John Bacsa; Jeffrey J Olson; Lanny S Liebeskind; Mark M Goodman

doi:10.1021/acsptsci.1c00062

Synthesis, Radiolabeling, and Biological Evaluation of the trans-Stereoisomers of 1-Amino-3-(fluoro-¹⁸F)-4-fluorocyclopentane-1-carboxylic Acid as PET Imaging Agents

ACS Pharmacol Transl Sci. 2021 Apr 5;4(3):1195-1203. doi: 10.1021/acsptsci.1c00062. eCollection 2021 Jun 11.

Authors

Thomas C Pickel^{1

2}, Gouthami Pashikanti¹, Ronald J Voll^{3

4}, Weiping Yu^{3

4}, Zhaobin Zhang³, Jonathon A Nye^{3

4}, John Bacsa^{2

3

1

4}, Jeffrey J Olson³, Lanny S Liebeskind¹, Mark M Goodman^{3

4}

Affiliations

¹ Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, United States.
² Medicinal Chemistry, Biotherapeutic and Medicinal Science, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.
³ Department of Radiology and Imaging Sciences, Department of Neurosurgery, School of Medicine, Emory University, 1364 Clifton Road NE, Atlanta, Georgia 30322, United States.
⁴ Center for Systems Imaging, Emory University, 1841 Clifton Road NE, Atlanta, Georgia 30322, United States.

Abstract

The enantiomeric non-natural cyclic amino acids (3R,4R)-1-amino-3-fluoro-4-(fluoro-¹⁸F)cyclopentane-1-carboxylic acid and (3S,4S)-1-amino-3-fluoro-4-(fluoro-¹⁸F)cyclopentane-1-carboxylic acid ([ ¹⁸ F]5) have been prepared as a racemic mixture in 1.3% decay corrected radiochemical yield and in greater than 99% radiochemical purity. [ ¹⁸ F]5 is transported primarily via system L with some transport occurring via system ASC, as assessed in rat 9L gliosarcoma, human U87 ΔEGFR glioblastoma, and human DU145 androgen-independent prostate carcinoma tumor cells. In rats bearing intracranial 9L gliosarcoma, [ ¹⁸ F]5 gave tumor to contralateral brain tissue ratios of up to 2.8. Biodistribution studies in healthy rats demonstrated that bladder accumulation is delayed until 10 min postinjection.