Imaging Glioblastoma With 18F-Fluciclovine Amino Acid Positron Emission Tomography
IntroductionConventional methods of imaging brain tumors fail to assess metabolically active tumor regions, which limits their capabilities for tumor detection, localization, and response assessment. Positron emission tomography (PET) with 18F-fluciclovine (fluciclovine) provides regional assessment...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.829050/full |
| _version_ | 1818939510334947328 |
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| author | Matthew L. Scarpelli Debbie R. Healey Shwetal Mehta C. Chad Quarles |
| author_facet | Matthew L. Scarpelli Debbie R. Healey Shwetal Mehta C. Chad Quarles |
| author_sort | Matthew L. Scarpelli |
| collection | DOAJ |
| description | IntroductionConventional methods of imaging brain tumors fail to assess metabolically active tumor regions, which limits their capabilities for tumor detection, localization, and response assessment. Positron emission tomography (PET) with 18F-fluciclovine (fluciclovine) provides regional assessment of amino acid uptake in tumors that could overcome some of the limitations of conventional imaging. However, the biological basis of enhanced fluciclovine uptake is insufficiently characterized in brain tumors, which confounds clinical interpretation and application. This study sought to address this gap by correlating multiple biologic quantities with fluciclovine PET uptake across a range of human glioblastoma xenograft models.MethodsThirty-one rats underwent orthotopic implantations with one of five different human glioblastoma cell lines. After tumors were established, fluciclovine PET and magnetic resonance imaging (MRI) scans were performed. The fluciclovine tumor-to-normal-brain (TN) uptake ratio was used to quantify fluciclovine uptake. MRI scans were used to assess tumor volume and gadolinium enhancement status. Histologic assessments quantified tumor cell proliferation, tumor cell density, and tumor cell amino acid transporters (LAT1 and ASCT2). Multivariate linear regression models related fluciclovine uptake with the other measured quantities.ResultsWithin the multivariate regression, the fluciclovine TN uptake ratio (measured 15 to 35 minutes after fluciclovine injection) was most strongly associated with tumor ASCT2 levels (β=0.64; P=0.001). The fluciclovine TN uptake ratio was also significantly associated with tumor volume (β=0.45; P=0.001) and tumor enhancement status (β=0.40; P=0.01). Tumor cell proliferation, tumor cell density, and LAT1 levels were not significantly associated with fluciclovine uptake in any of the multivariate models. In general, both enhancing and non-enhancing tumors could be visualized on fluciclovine PET images, with the median TN uptake ratio across the five tumor lines being 2.4 (range 1.1 to 8.9).ConclusionsIncreased fluciclovine PET uptake was associated with increased levels of the amino acid transporter ASCT2, suggesting fluciclovine PET may be useful for assessing brain tumor amino acid metabolism. Fluciclovine PET uptake was elevated in both enhancing and non-enhancing tumors but the degree of uptake was greater in larger tumors and tumors with enhancement, indicating these variables could confound fluciclovine metabolic measurements if not accounted for. |
| first_indexed | 2024-12-20T06:24:54Z |
| format | Article |
| id | doaj.art-3ad7017d7b964e09b30a6da262c0a167 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-20T06:24:54Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-3ad7017d7b964e09b30a6da262c0a1672022-12-21T19:50:20ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-01-011210.3389/fonc.2022.829050829050Imaging Glioblastoma With 18F-Fluciclovine Amino Acid Positron Emission TomographyMatthew L. Scarpelli0Debbie R. Healey1Shwetal Mehta2C. Chad Quarles3School of Health Sciences, Purdue University, West Lafayette, IN, United StatesBarrow Neuroimaging Innovation Center, Barrow Neurological Institute, Phoenix, AZ, United StatesIvy Brain Tumor Center, Barrow Neurological Institute, Phoenix, AZ, United StatesBarrow Neuroimaging Innovation Center, Barrow Neurological Institute, Phoenix, AZ, United StatesIntroductionConventional methods of imaging brain tumors fail to assess metabolically active tumor regions, which limits their capabilities for tumor detection, localization, and response assessment. Positron emission tomography (PET) with 18F-fluciclovine (fluciclovine) provides regional assessment of amino acid uptake in tumors that could overcome some of the limitations of conventional imaging. However, the biological basis of enhanced fluciclovine uptake is insufficiently characterized in brain tumors, which confounds clinical interpretation and application. This study sought to address this gap by correlating multiple biologic quantities with fluciclovine PET uptake across a range of human glioblastoma xenograft models.MethodsThirty-one rats underwent orthotopic implantations with one of five different human glioblastoma cell lines. After tumors were established, fluciclovine PET and magnetic resonance imaging (MRI) scans were performed. The fluciclovine tumor-to-normal-brain (TN) uptake ratio was used to quantify fluciclovine uptake. MRI scans were used to assess tumor volume and gadolinium enhancement status. Histologic assessments quantified tumor cell proliferation, tumor cell density, and tumor cell amino acid transporters (LAT1 and ASCT2). Multivariate linear regression models related fluciclovine uptake with the other measured quantities.ResultsWithin the multivariate regression, the fluciclovine TN uptake ratio (measured 15 to 35 minutes after fluciclovine injection) was most strongly associated with tumor ASCT2 levels (β=0.64; P=0.001). The fluciclovine TN uptake ratio was also significantly associated with tumor volume (β=0.45; P=0.001) and tumor enhancement status (β=0.40; P=0.01). Tumor cell proliferation, tumor cell density, and LAT1 levels were not significantly associated with fluciclovine uptake in any of the multivariate models. In general, both enhancing and non-enhancing tumors could be visualized on fluciclovine PET images, with the median TN uptake ratio across the five tumor lines being 2.4 (range 1.1 to 8.9).ConclusionsIncreased fluciclovine PET uptake was associated with increased levels of the amino acid transporter ASCT2, suggesting fluciclovine PET may be useful for assessing brain tumor amino acid metabolism. Fluciclovine PET uptake was elevated in both enhancing and non-enhancing tumors but the degree of uptake was greater in larger tumors and tumors with enhancement, indicating these variables could confound fluciclovine metabolic measurements if not accounted for.https://www.frontiersin.org/articles/10.3389/fonc.2022.829050/fullpositron emission tomography18F-FACBCfluciclovineASCT2amino acid metabolismPET imaging |
| spellingShingle | Matthew L. Scarpelli Debbie R. Healey Shwetal Mehta C. Chad Quarles Imaging Glioblastoma With 18F-Fluciclovine Amino Acid Positron Emission Tomography Frontiers in Oncology positron emission tomography 18F-FACBC fluciclovine ASCT2 amino acid metabolism PET imaging |
| title | Imaging Glioblastoma With 18F-Fluciclovine Amino Acid Positron Emission Tomography |
| title_full | Imaging Glioblastoma With 18F-Fluciclovine Amino Acid Positron Emission Tomography |
| title_fullStr | Imaging Glioblastoma With 18F-Fluciclovine Amino Acid Positron Emission Tomography |
| title_full_unstemmed | Imaging Glioblastoma With 18F-Fluciclovine Amino Acid Positron Emission Tomography |
| title_short | Imaging Glioblastoma With 18F-Fluciclovine Amino Acid Positron Emission Tomography |
| title_sort | imaging glioblastoma with 18f fluciclovine amino acid positron emission tomography |
| topic | positron emission tomography 18F-FACBC fluciclovine ASCT2 amino acid metabolism PET imaging |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.829050/full |
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