Radiosynthesis and biological evaluation of N-[18F]labeled glutamic acid as a tumor metabolic imaging tracer

PLoS One. 2014 Mar 28;9(3):e93262. doi: 10.1371/journal.pone.0093262. eCollection 2014.

Abstract

We have previously reported that N-(2-[18F]fluoropropionyl)-L-methionine ([18F]FPMET) selectively accumulates in tumors. However, due to the poor pharmacokinetics of [18F]FPMET in vivo, the potential clinical translation of this observation is hampered. In this study, we rationally designed and synthesized [18F] or [11C]labeled N-position L-glutamic acid analogues for tumor imaging. N-(2-[18F]fluoropropionyl)-L-glutamic acid ([18F]FPGLU) was synthesized with a 30±10% (n = 10, decay-corrected) overall radiochemical yield and a specific activity of 40±25 GBq/μmol (n = 10) after 130 min of radiosynthesis. In vitro cell experiments showed that [18F]FPGLU was primarily transported through the XAG(-) system and was not incorporated into protein. [18F]FPGLU was stable in urine, tumor tissues, and blood. We were able to use [18F]FPGLU in PET imaging and obtained high tumor to background ratios when visualizing tumors tissues in animal models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Diagnostic Imaging / methods
  • Glutamic Acid / chemistry*
  • Isotope Labeling / methods
  • Methionine / chemistry
  • Mice
  • Positron-Emission Tomography / methods
  • Radiopharmaceuticals / chemistry*
  • Tissue Distribution / physiology

Substances

  • Radiopharmaceuticals
  • Glutamic Acid
  • Methionine

Grants and funding

National High Technology Research and Development Program of China (863 Program, No. 2008AA02Z430, NO. 81371584), the National Natural Science Foundation (No. 30970856, No. 81371584), the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry ([2010]609), Science and Technology Planning Project of Guangzhou (2011J5200025), and Sun Yat-Sen University (No. 80000-3126132). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.