TY - JOUR
T1 - Pilot preclinical and clinical evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-Glutamate (18F-FSPG) for PET/CT imaging of intracranial malignancies
AU - Mittra, Erik S.
AU - Koglin, Norman
AU - Mosci, Camila
AU - Kumar, Meena
AU - Hoehne, Aileen
AU - Keu, Khun Visith
AU - Iagaru, Andrei H.
AU - Mueller, Andre
AU - Berndt, Mathias
AU - Bullich, Santiago
AU - Friebe, Matthias
AU - Schmitt-Willich, Heribert
AU - Gekeler, Volker
AU - Fels, Lüder M.
AU - Bacher-Stier, Claudia
AU - Hyuk Moon, Dae
AU - Chin, Frederick T.
AU - Stephens, Andrew W.
AU - Dinkelborg, Ludger M.
AU - Gambhir, Sanjiv S.
N1 - Funding Information:
The authors have the following interests: The study was sponsored by Bayer Healthcare. NK, AM, MB, HSW, VG, MF, LMD, AWS, LMF, and CBS were employed by Bayer Pharma AG at the time of study conduct. NK, AM, MB, SB, HSW, MF, LMD, and AWS are currently employed by Piramal Imaging GmbH. On the basis of prior work, patent applications were filed from Bayer to cover the compound investigated here. The compound rights were transferred to Piramal Imaging. The investigated compound is currently in clinical development and is not marketed. NK, AM, MB, HSW, AWS, MF, LMD are co-inventors of the compound and/or have ownership interests in Piramal Imaging. DHM, ESM and SSG received research grants from Bayer Healthcare and Piramal Imaging related to this compound. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.
Funding Information:
The clinical work was supported by funding from Bayer HealthCare, Inc. / Piramal Imaging as part of a sponsored clinical research trial. We would like to thank the research study participants and families, our referring physicians, our clinical research coordinators, the Radiochemistry Facility and staff, in particular Dr. Bin Shen, Amit Hetstron, and So-Hee Kim, all our PET/CT technologists, and the research staff at Bayer HealthCare / Piramal Imaging Berlin for their assistance in this project. We would also like to thank the Ben and Catherine Ivy Foundation (SSG), and the NCI In Vivo Cellular & Molecular Imaging Center (ICMIC P50) (SSG) for funding support.
Publisher Copyright:
© 2016 Mittra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/2
Y1 - 2016/2
N2 - 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, 18FFSPG 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.
AB - 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, 18FFSPG 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.
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U2 - 10.1371/journal.pone.0148628
DO - 10.1371/journal.pone.0148628
M3 - Article
C2 - 26890637
AN - SCOPUS:84960900352
VL - 11
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 2
M1 - e0148628
ER -