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

PURPOSE: (S)-4-(3-[(18)F]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 x(C)(-) transporter activity. This study was performed to assess the feasibility of 18F-FSPG for ima...

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Autores principales: Mittra, Erik S., Koglin, Norman, Mosci, Camila, Kumar, Meena, Hoehne, Aileen, Keu, Khun Visith, Iagaru, Andrei H., Mueller, Andre, Berndt, Mathias, Bullich, Santiago, Friebe, Matthias, Schmitt-Willich, Heribert, Gekeler, Volker, Fels, Lüder M., Bacher-Stier, Claudia, Moon, Dae Hyuk, Chin, Frederick T., Stephens, Andrew W., Dinkelborg, Ludger M., Gambhir, Sanjiv S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758607/
https://www.ncbi.nlm.nih.gov/pubmed/26890637
http://dx.doi.org/10.1371/journal.pone.0148628
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author Mittra, Erik S.
Koglin, Norman
Mosci, Camila
Kumar, Meena
Hoehne, Aileen
Keu, Khun Visith
Iagaru, Andrei H.
Mueller, Andre
Berndt, Mathias
Bullich, Santiago
Friebe, Matthias
Schmitt-Willich, Heribert
Gekeler, Volker
Fels, Lüder M.
Bacher-Stier, Claudia
Moon, Dae Hyuk
Chin, Frederick T.
Stephens, Andrew W.
Dinkelborg, Ludger M.
Gambhir, Sanjiv S.
author_facet Mittra, Erik S.
Koglin, Norman
Mosci, Camila
Kumar, Meena
Hoehne, Aileen
Keu, Khun Visith
Iagaru, Andrei H.
Mueller, Andre
Berndt, Mathias
Bullich, Santiago
Friebe, Matthias
Schmitt-Willich, Heribert
Gekeler, Volker
Fels, Lüder M.
Bacher-Stier, Claudia
Moon, Dae Hyuk
Chin, Frederick T.
Stephens, Andrew W.
Dinkelborg, Ludger M.
Gambhir, Sanjiv S.
author_sort Mittra, Erik S.
collection PubMed
description PURPOSE: (S)-4-(3-[(18)F]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 x(C)(-) 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
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spelling pubmed-47586072016-02-26 Pilot Preclinical and Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-Glutamate (18F-FSPG) for PET/CT Imaging of Intracranial Malignancies Mittra, Erik S. Koglin, Norman Mosci, Camila Kumar, Meena Hoehne, Aileen Keu, Khun Visith Iagaru, Andrei H. Mueller, Andre Berndt, Mathias Bullich, Santiago Friebe, Matthias Schmitt-Willich, Heribert Gekeler, Volker Fels, Lüder M. Bacher-Stier, Claudia Moon, Dae Hyuk Chin, Frederick T. Stephens, Andrew W. Dinkelborg, Ludger M. Gambhir, Sanjiv S. PLoS One Research Article PURPOSE: (S)-4-(3-[(18)F]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 x(C)(-) 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 Public Library of Science 2016-02-18 /pmc/articles/PMC4758607/ /pubmed/26890637 http://dx.doi.org/10.1371/journal.pone.0148628 Text en © 2016 Mittra et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Mittra, Erik S.
Koglin, Norman
Mosci, Camila
Kumar, Meena
Hoehne, Aileen
Keu, Khun Visith
Iagaru, Andrei H.
Mueller, Andre
Berndt, Mathias
Bullich, Santiago
Friebe, Matthias
Schmitt-Willich, Heribert
Gekeler, Volker
Fels, Lüder M.
Bacher-Stier, Claudia
Moon, Dae Hyuk
Chin, Frederick T.
Stephens, Andrew W.
Dinkelborg, Ludger M.
Gambhir, Sanjiv S.
Pilot Preclinical and Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-Glutamate (18F-FSPG) for PET/CT Imaging of Intracranial Malignancies
title Pilot Preclinical and Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-Glutamate (18F-FSPG) for PET/CT Imaging of Intracranial Malignancies
title_full Pilot Preclinical and Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-Glutamate (18F-FSPG) for PET/CT Imaging of Intracranial Malignancies
title_fullStr Pilot Preclinical and Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-Glutamate (18F-FSPG) for PET/CT Imaging of Intracranial Malignancies
title_full_unstemmed Pilot Preclinical and Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-Glutamate (18F-FSPG) for PET/CT Imaging of Intracranial Malignancies
title_short Pilot Preclinical and Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-Glutamate (18F-FSPG) for PET/CT Imaging of Intracranial Malignancies
title_sort pilot preclinical and clinical evaluation of (4s)-4-(3-[18f]fluoropropyl)-l-glutamate (18f-fspg) for pet/ct imaging of intracranial malignancies
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758607/
https://www.ncbi.nlm.nih.gov/pubmed/26890637
http://dx.doi.org/10.1371/journal.pone.0148628
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