title: Pilot Preclinical and Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-Glutamate (18F-FSPG) for PET/CT Imaging of Intracranial Malignancies.
abstract: OBJECTIVE
  (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.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01186601.
authors.affiliation: Molecular Imaging Program, Department of Radiology, Stanford Hospital and Clinics, Stanford, CA, United States of America.
authors.forename: Erik S
authors.initials: ES
authors.lastname: Mittra
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Norman
authors.initials: N
authors.lastname: Koglin
authors.affiliation: Molecular Imaging Program, Department of Radiology, Stanford Hospital and Clinics, Stanford, CA, United States of America.
authors.forename: Camila
authors.initials: C
authors.lastname: Mosci
authors.affiliation: Molecular Imaging Program, Department of Radiology, Stanford Hospital and Clinics, Stanford, CA, United States of America.
authors.forename: Meena
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Molecular Imaging Program, Department of Radiology, Stanford Hospital and Clinics, Stanford, CA, United States of America.
authors.forename: Aileen
authors.initials: A
authors.lastname: Hoehne
authors.affiliation: Molecular Imaging Program, Department of Radiology, Stanford Hospital and Clinics, Stanford, CA, United States of America.
authors.forename: Khun Visith
authors.initials: KV
authors.lastname: Keu
authors.affiliation: Molecular Imaging Program, Department of Radiology, Stanford Hospital and Clinics, Stanford, CA, United States of America.
authors.forename: Andrei H
authors.initials: AH
authors.lastname: Iagaru
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Mueller
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Berndt
authors.affiliation: Piramal Imaging GmbH, Berlin, Germany.
authors.forename: Santiago
authors.initials: S
authors.lastname: Bullich
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Friebe
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Heribert
authors.initials: H
authors.lastname: Schmitt-Willich
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Gekeler
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Lüder M
authors.initials: LM
authors.lastname: Fels
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bacher-Stier
authors.affiliation: Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Dae Hyuk
authors.initials: DH
authors.lastname: Moon
authors.affiliation: Molecular Imaging Program, Department of Radiology, Stanford Hospital and Clinics, Stanford, CA, United States of America.
authors.forename: Frederick T
authors.initials: FT
authors.lastname: Chin
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Stephens
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Ludger M
authors.initials: LM
authors.lastname: Dinkelborg
authors.affiliation: Molecular Imaging Program, Department of Radiology, Stanford Hospital and Clinics, Stanford, CA, United States of America.|Bio-X Program, Department of Bioengineering, Department of Materials Science & Engineering, Stanford University, Stanford, CA, United States of America.
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000556:secondary; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D019788:Fluorodeoxyglucose F18; D005909:Glioblastoma / Q000175:diagnosis; D018698:Glutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D064593:Heterografts; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals; D051381:Rats; D014057:Tomography, X-Ray Computed / Q000379:methods; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C545932:(18F)fluoroethyltyrosine; D018698:Glutamic Acid; D014443:Tyrosine