Pilot Preclinical and Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-Glutamate (18F-FSPG) for PET/CT Imaging of Intracranial Malignancies

PLoS One. 2016 Feb 18;11(2):e0148628. doi: 10.1371/journal.pone.0148628. eCollection 2016.

Abstract

Purpose: (S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid (18F-FSPG) is a novel radiopharmaceutical for Positron Emission Tomography (PET) imaging. It is a glutamate analogue that can be used to measure xC- transporter activity. This study was performed to assess the feasibility of 18F-FSPG for imaging orthotopic brain tumors in small animals and the translation of this approach in human subjects with intracranial malignancies.

Experimental design: For the small animal study, GS9L glioblastoma cells were implanted into brains of Fischer rats and studied with 18F-FSPG, the 18F-labeled glucose derivative 18F-FDG and with the 18F-labeled amino acid derivative 18F-FET. For the human study, five subjects with either primary or metastatic brain cancer were recruited (mean age 50.4 years). After injection of 300 MBq of 18F-FSPG, 3 whole-body PET/Computed Tomography (CT) scans were obtained and safety parameters were measured. The three subjects with brain metastases also had an 18F-FDG PET/CT scan. Quantitative and qualitative comparison of the scans was performed to assess kinetics, biodistribution, and relative efficacy of the tracers.

Results: In the small animals, the orthotopic brain tumors were visualized well with 18F-FSPG. The high tumor uptake of 18F-FSPG in the GS9L model and the absence of background signal led to good tumor visualization with high contrast (tumor/brain ratio: 32.7). 18F-FDG and 18F-FET showed T/B ratios of 1.7 and 2.8, respectively. In the human pilot study, 18F-FSPG was well tolerated and there was similar distribution in all patients. All malignant lesions were positive with 18F-FSPG except for one low-grade primary brain tumor. In the 18F-FSPG-PET-positive tumors a similar T/B ratio was observed as in the animal model.

Conclusions: 18F-FSPG is a novel PET radiopharmaceutical that demonstrates good uptake in both small animal and human studies of intracranial malignancies. Future studies on larger numbers of subjects and a wider array of brain tumors are planned.

Trial registration: ClinicalTrials.gov NCT01186601.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / secondary
  • Case-Control Studies
  • Cell Line, Tumor
  • Disease Models, Animal
  • Female
  • Fluorodeoxyglucose F18
  • Glioblastoma / diagnosis
  • Glutamic Acid / analogs & derivatives*
  • Glutamic Acid / chemistry
  • Heterografts
  • Humans
  • Male
  • Middle Aged
  • Positron-Emission Tomography* / methods
  • Radiopharmaceuticals*
  • Rats
  • Tomography, X-Ray Computed* / methods
  • Tyrosine / analogs & derivatives*
  • Tyrosine / chemistry

Substances

  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • (18F)fluoroethyltyrosine
  • Glutamic Acid
  • Tyrosine

Associated data

  • ClinicalTrials.gov/NCT01186601

Grant support

The study was sponsored by Bayer Healthcare. Bayer Healthcare provided support in the form of salaries for authors [NK, AM, MB, HSW, VG, MF, LMD, AWS, LMF, and CBS], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding was also provided by the Ben and Catherine Ivy Foundation (SSG), and the NCI In Vivo Cellular & Molecular Imaging Center (ICMIC P50) (SSG).