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A Metabolically Stable Boron-Derived Tyrosine Serves as a Theranostic Agent for Positron Emission Tomography Guided Boron Neutron Capture Therapy
journal contribution
posted on 2019-10-14, 11:38 authored by Jiyuan Li, Yaxin Shi, Zizhu Zhang, Hui Liu, Lixin Lang, Tong Liu, Xiaoyuan Chen, Zhibo LiuBoronophenylalanine
(BPA) is the dominant boron delivery agent for boron neutron capture
therapy (BNCT), and [18F]FBPA has been developed to assist
the treatment planning for BPA-BNCT. However, the clinical application
of BNCT has been limited by its inadequate tumor specificity due to
the metabolic instability. In addition, the distinctive molecular
structures between [18F]FBPA and BPA can be of concern
as [18F]FBPA cannot quantitate boron concentration of BPA
in a real-time manner. In this study, a metabolically stable boron-derived
tyrosine (denoted as fluoroboronotyrosine, FBY) was developed as a
theranostic agent for both boron delivery and cancer diagnosis, leading
to PET imaging-guided BNCT of cancer. [18F]FBY was synthesized
in high radiochemical yield (50%) and high radiochemical purity (98%).
FBY showed high similarity with natural tyrosine. As shown in in vitro
assays, the uptake of FBY in murine melanoma B16-F10 cells was L-type
amino acid transporter (LAT-1) dependent and reached up to 128 μg/106 cells. FBY displayed high stability in PBS solution. [18F]FBY PET showed up to 6 %ID/g in B16-F10 tumor and notably
low normal tissue uptake (tumor/muscle = 3.16 ± 0.48; tumor/blood
= 3.13 ± 0.50; tumor/brain = 14.25 ± 1.54). Moreover, administration
of [18F]FBY tracer along with a therapeutic dose of FBY
showed high accumulation in B16-F10 tumor and low normal tissue uptake.
Correlation between PET-image and boron biodistribution was established,
indicating the possibility of estimating boron concentration via a
noninvasive approach. At last, with thermal neutron irradiation, B16-F10
tumor-bearing mice injected with FBY showed significantly prolonged
median survival without exhibiting obvious systemic toxicity. In conclusion,
FBY holds great potential as an efficient theranostic agent for imaging-guided
BNCT by offering a possible solution of measuring local boron concentration
through PET imaging.
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boron concentrationLATquantitate boron concentrationB 16-F tumorPBSB 16-F tumor-bearing micetheranostic agenttissue uptakeFBYmurine melanoma B 16-F cellsBPA-BNCTBPAMetabolically Stable Boron-Derived Tyrosineboron delivery agentIDPositron Emission Tomography Guided Boron Neutron Capture Therapy BoronophenylalaninePET imaging-guided BNCT
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