¹⁸F-Boramino acid PET/CT in healthy volunteers and glioma patients.

Abstract

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. 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. 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). 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. clinicaltrials.gov (NCT03980431).