Synthesis and evaluation of [18F]1-amino-3-fluorocyclobutane-1-carboxylic acid to image brain tumors

J Nucl Med. 1999 Feb;40(2):331-8.

Abstract

We have developed a new tumor-avid amino acid, 1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC), labeled with 18F for nuclear medicine imaging.

Methods: [18F]FACBC was prepared with high specific activity (no carrier added [NCA]) and was evaluated for its potential in tumor localization. A comparative study was performed for [18F]FACBC and [18F]2-fluorodeoxyglucose (FDG) in which the uptake of each agent in 9L gliosarcoma (implanted intracerebrally in Fisher 344 rats) was measured. In addition, the first human PET study of [18F]FACBC was performed on a patient with residual glioblastoma multiforme. Quantitative brain images of the patient were obtained by using a Siemens 921 47-slice PET imaging system.

Results: In the rat brain, the initial level of radioactivity accumulation after injection of [18F]FACBC was low (0.11 percentage injected dose per gram [%ID/g]) at 5 min and increased slightly to 0.26 %ID/g at 60 min. The tumor uptake exhibited a maximum at 60 min (1.72 %ID/g), resulting in a tumor-to-brain ratio increase of 5.58 at 5 min to 6.61 at 60 min. In the patient, the uptake of [18F]FACBC in the tumor exhibited a maximum concentration of 146 nCi/mL at 35 min after injection. The uptake of radioactivity in the normal brain tissue was low, 21 nCi/mL at 15 min after injection, and gradually increased to 29 nCi/mL at 60 min after injection. The ratio of tumor to normal tissue was 6 at 20 min after injection. The [18F]FACBC PET scan showed intense uptake in the left frontal region of the brain.

Conclusion: The amino acid FACBC can be radiofluorinated for clinical use. [18F]FACBC is a potential PET tracer for tumor imaging.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Brain Neoplasms / diagnostic imaging*
  • Carboxylic Acids* / chemical synthesis
  • Carboxylic Acids* / pharmacokinetics
  • Carboxylic Acids* / toxicity
  • Cyclobutanes* / chemical synthesis
  • Cyclobutanes* / pharmacokinetics
  • Cyclobutanes* / toxicity
  • Fluorodeoxyglucose F18
  • Humans
  • Male
  • Middle Aged
  • Radiation Dosage
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / toxicity
  • Rats
  • Rats, Inbred F344
  • Rats, Sprague-Dawley
  • Tissue Distribution
  • Tomography, Emission-Computed*

Substances

  • Carboxylic Acids
  • Cyclobutanes
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • fluciclovine F-18