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

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.

• Authors: Erik S Mittra, Norman Koglin, Camila Mosci, Meena Kumar, Aileen Hoehne, Khun Visith Keu, Andrei H Iagaru, Andre Mueller, Mathias Berndt, Santiago Bullich, Matthias Friebe, Heribert Schmitt-Willich, Volker Gekeler, Lüder M Fels, Claudia Bacher-Stier, Dae Hyuk Moon, Frederick T Chin, Andrew W Stephens, Ludger M Dinkelborg, Sanjiv S Gambhir
• Journal: PloS one (PLoS One) Vol. 11 Issue 2 Pg. e0148628 ( 2016) ISSN: 1932-6203 [Electronic] United States
• PMID: 26890637 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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