Effect of α-Methyl versus α-Hydrogen Substitution on Brain Availability and Tumor Imaging Properties of Heptanoic [F-18]Fluoroalkyl Amino Acids for Positron Emission Tomography (PET).
Effect of α-Methyl versus α-Hydrogen Substitution on Brain Availability and Tumor Imaging Properties of Heptanoic [F-18]Fluoroalkyl Amino Acids for Positron Emission Tomography (PET).
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DOI：
10.1021/acs.jmedchem.6b00189
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发表时间：
2016-04-14
影响因子：
7.3
通讯作者：
McConathy J
中科院分区：
文献类型：
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作者：
Bouhlel A;Alyami W;Li A;Yuan L;Rich K;McConathy J
其中涉及氟烷基取代氨基酸类单体两个[18 f]不同的只有一个甲基的存在与否对α碳,(S) 2-amino-7 - [18 f] fluoro-2-methylheptanoic酸((S) - [18 f] FAMHep (S) - [18 f] 14)和(S) 2-amino-7 - [18 f] -fluoroheptanoic酸((S) - [18 f] FAHep (S) - [18 f] 15),开发了大脑肿瘤成像和比较完善的系统L氨基酸示踪,O - (2 - [18 f] fluoroethyl) -L-tyrosine ([18 f]场效应晶体管),推迟大脑神经胶质瘤肿瘤(印度生物技术部)小鼠模型的高档。细胞摄取、生物分布和PET/CT成像研究显示，DBT细胞对这些示踪剂的氨基酸转运存在差异。系统L氨基酸转运体识别(S)-[18F]15而不识别(S)-[18F]14，导致正常大脑中α-氢取代类似物(S)-[18F]15的摄取增加约8 - 10倍。(S)-[18F]15在DBT肿瘤模型中具有与(S)-[18F]FET相似的成像特性，而(S)-[18F]14由于正常脑的摄取低得多而具有更高的肿瘤脑比。这些结果对α-烷基和α，α-二烷基取代氨基酸在脑肿瘤成像中的应用具有重要的指导意义。
Two [18F]fluoroalkyl substituted amino acids differing only by the presence or absence of a methyl group on the α-carbon, (S)-2-amino-7-[18F]fluoro-2-methylheptanoic acid ((S)-[18F]FAMHep, (S)-[18F]14) and (S)-2-amino-7-[18F]-fluoroheptanoic acid ((S)-[18F]FAHep, (S)-[18F]15), were developed for brain tumor imaging and compared to the well-established system L amino acid tracer, O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET), in the delayed brain tumor (DBT) mouse model of high-grade glioma. Cell uptake, biodistribution, and PET/CT imaging studies showed differences in amino acid transport of these tracer by DBT cells. Recognition of (S)-[18F]15 but not (S)-[18F]14 by system L amino acid transporters led to approximately 8–10-fold higher uptake of the α-hydrogen substituted analogue (S)-[18F]15 in normal brain. (S)-[18F]15 had imaging properties similar to those of (S)-[18F]FET in the DBT tumor model while (S)-[18F]14 afforded higher tumor to brain ratios due to much lower uptake by normal brain. These results have important implications for the future development of α-alkyl and α,α-dialkyl substituted amino acids for brain tumor imaging.