Zhu Li1, Ziren Kong2, Junyi Chen3, Jiyuan Li3, Nan Li1, Zhi Yang4, Yu Wang5, Zhibo Liu6,7. 1. Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of nuclear medicine, Peking University Cancer Hospital & Institute, Beijing, 100871, China. 2. Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 3. Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China. 4. Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of nuclear medicine, Peking University Cancer Hospital & Institute, Beijing, 100871, China. pekyz@163.com. 5. Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. ywang@pumch.cn. 6. Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China. zbliu@pku.edu.cn. 7. Peking University-Tsinghua University Center for Life Sciences, Beijing, 100871, China. zbliu@pku.edu.cn.
Abstract
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 (SUVmax) 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 SUVmax, 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).
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 gliomapatients. 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 (SUVmax) 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 SUVmax, 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 gliomapatients and may provide imaging guidance for further boron neutron capture therapy of gliomas. TRIAL REGISTRATION: clinicaltrials.gov (NCT03980431).
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