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《第十届全国化学生物学学术会议报告摘要集(青年科学家论坛)》2017年
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Boramino Acid as A Theranostic Agent Unifies BNCT Precision Therapy and PET Molecular Imaging

Jiyuan Li  Qinyang Wang  Chunhong Wang  Yuxiang Han  Zhibo Liu  
【摘要】:OBJECTIVE A new class of amino acid mimics—boramino acids(BAAs)—are described here as theranostic agents for PET imaging guided BNCT cancer treatment.1 The structure of a BAA is identical to that of the corresponding natural amino acid, except for an exotic replacement of the carboxylate with trifluoroborate. Cellular studies demonstrate the cell uptake of BAA is strongly mediated to amino acid transporter, of which the abnormal expression is often associated with cancer. In addition, animal studies of F-18 labeled BAA(_(18)F-BAA) show high tumor-specific accumulation with PET(positron emission tomography), suggesting that BAA holds great promise for the development of new PET imaging probes and AAT-targeting boron agents for BNCT cancer therapy.METHOD A boron-derived Tyrosine(B-Tyr) derivative was synthesized to mimic Tyr, of which the transportation depends on L-type amino acid transporter(LAT). _(18)F-_(19)F isotope exchange reaction was conducted for radiolabeling and quality control was performed by both HPLC and radioTLC.2,3 The metabolic stability of B-Tyr was assessed both in vitro and in vivo. PET imaging were performed in mice bearing U87 xenografts, and _(18)F-B-Tyr is co-injected with 10 mg of unlabeled boron-derived Tyr. The animals are sacrificed right after PET scan, and organs are collected for ICP analysis.RESULT As shown in Figure 1, _(18)F-B-Tyr shows high accumulation in U87 tumor(5.3 ±1.3 %ID/g)at 60 min post injection but demonstrates low uptake in the rest of the body(liver, 2.41 ± 0.36%ID/g; muscle, 1.98 ± 0.54 %ID/g; brain, 0.35 ± 0.13 %ID/g and blood, 1.19 ±0.47%ID/g). The tracer had predominant renal clearance but with low kidney retention. The following ICP analysis is correlated with PET imaging and shows high boron accumulation in tumor(66.7 ± 11.5 ppm)with good selectivity on healthy tissues(liver, 13.5 ± 2.1 ppm; muscle, 12.1 ± 1.9 ppm; brain,5.9± 1.3 ppm and blood, 7.8 ± 2.0 ppm).CONCLUSION A boron-derived Tyr derivative was developed and evaluated for PET-guided BNCT10 th CNCCB Topic II: Molecular Imaging and Bioanalytical Chemistry treatment. Administration of _(18)F-B-Tyr allowed for clear visualization of tumor xenografts, and also delivers high concentration of boron atoms into tumor that can be promising for BNCT treatment.

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