18F-Boramino acid PET/CT in healthy volunteers and glioma patients
Purpose In this work, the safety, biodistribution, and radiation dosimetry of large neutral amino acid transporter type-1 (LAT-1) targeting PET tracer 18F-trifluorobborate-derived tyrosine (denoted as 18F-FBY) has been investigated. It is designed as a first-in-human study in healthy volunteers and to assay LAT-1 expression level in glioma patients. Methods Six healthy volunteers (3 M, 3 F) underwent whole-body PET acquisitions at multiple time points after bolus injection of 18F-FBY. Regions of interest (ROIs) were mapped manually on major organs, and then the time-activity curves (TACs) were obtained. Dosimetry was calculated with the OLINDA/EXM software. Thirteen patients who were suspected of glioma were scanned with PET/CT at 30 min after 18F-FBY injection. Within 7 days after PET/CT, the tumor was removed surgically, and LAT-1 immunohistochemical staining for LAT-1 was performed on tumor samples and correlated with 18F-FBY PET imaging. Results 18F-FBY was well tolerated by all healthy volunteers, and no adverse symptoms were observed or reported. 18F-FBY is rapidly cleared from the blood circulation and excreted mainly through the kidneys and urinary tract. The effective dose (ED) was 0.0039 ± 0.0006 mSv/MBq. In 14 surgical confirmed gliomas (one of the patiens had two gliomas), 18F-FBY uptake increased consistently with tumor grade, with maximum standard uptake values ($ SUV_{max} $) of 0.28 ± 0.14 and 2.84 ± 0.46 and tumor-to-normal contralateral activity (T/N) ratio of 2.30 ± 1.26 and 24.56 ± 6.32 in low- and high-grade tumors, respectively. In addition to the significant difference in the uptakes between low- and high-grade gliomas (P < 0.001), the immunohistochemical staining confirmed the positive correlations between the $ SUV_{max} $, LAT-1 expression (r2 = 0.80, P < 0.001), and Ki-67 labeling index (r2 = 0.79, P < 0.001). Conclusion 18F-FBY is a PET tracer with favorable dosimetry profile and pharmacokinetics. It has the potential to assay LAT-1 expression in glioma patients and may provide imaging guidance for further boron neutron capture therapy of gliomas. Trial registration clinicaltrials.gov (NCT03980431).
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:48 |
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| Enthalten in: |
European journal of nuclear medicine & molecular imaging - 48(2021), 10 vom: 15. Feb., Seite 3113-3121 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Zhu [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
Boramino acid |
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| Anmerkungen: |
© The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature 2021 |
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| doi: |
10.1007/s00259-021-05212-7 |
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OLC2127633857 |
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| 520 | |a Purpose In this work, the safety, biodistribution, and radiation dosimetry of large neutral amino acid transporter type-1 (LAT-1) targeting PET tracer 18F-trifluorobborate-derived tyrosine (denoted as 18F-FBY) has been investigated. It is designed as a first-in-human study in healthy volunteers and to assay LAT-1 expression level in glioma patients. Methods Six healthy volunteers (3 M, 3 F) underwent whole-body PET acquisitions at multiple time points after bolus injection of 18F-FBY. Regions of interest (ROIs) were mapped manually on major organs, and then the time-activity curves (TACs) were obtained. Dosimetry was calculated with the OLINDA/EXM software. Thirteen patients who were suspected of glioma were scanned with PET/CT at 30 min after 18F-FBY injection. Within 7 days after PET/CT, the tumor was removed surgically, and LAT-1 immunohistochemical staining for LAT-1 was performed on tumor samples and correlated with 18F-FBY PET imaging. Results 18F-FBY was well tolerated by all healthy volunteers, and no adverse symptoms were observed or reported. 18F-FBY is rapidly cleared from the blood circulation and excreted mainly through the kidneys and urinary tract. The effective dose (ED) was 0.0039 ± 0.0006 mSv/MBq. In 14 surgical confirmed gliomas (one of the patiens had two gliomas), 18F-FBY uptake increased consistently with tumor grade, with maximum standard uptake values ($ SUV_{max} $) of 0.28 ± 0.14 and 2.84 ± 0.46 and tumor-to-normal contralateral activity (T/N) ratio of 2.30 ± 1.26 and 24.56 ± 6.32 in low- and high-grade tumors, respectively. In addition to the significant difference in the uptakes between low- and high-grade gliomas (P < 0.001), the immunohistochemical staining confirmed the positive correlations between the $ SUV_{max} $, LAT-1 expression (r2 = 0.80, P < 0.001), and Ki-67 labeling index (r2 = 0.79, P < 0.001). Conclusion 18F-FBY is a PET tracer with favorable dosimetry profile and pharmacokinetics. It has the potential to assay LAT-1 expression in glioma patients and may provide imaging guidance for further boron neutron capture therapy of gliomas. Trial registration clinicaltrials.gov (NCT03980431) | ||
| 650 | 4 | |a Boramino acid | |
| 650 | 4 | |a Large neutral amino acid transporter type-1 (LAT-1) | |
| 650 | 4 | |a F-FBY | |
| 650 | 4 | |a PET/CT | |
| 650 | 4 | |a Glioma | |
| 700 | 1 | |a Kong, Ziren |4 aut | |
| 700 | 1 | |a Chen, Junyi |4 aut | |
| 700 | 1 | |a Li, Jiyuan |4 aut | |
| 700 | 1 | |a Li, Nan |4 aut | |
| 700 | 1 | |a Yang, Zhi |4 aut | |
| 700 | 1 | |a Wang, Yu |4 aut | |
| 700 | 1 | |a Liu, Zhibo |0 (orcid)0000-0002-5587-4165 |4 aut | |
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