Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Katzin Diagnostic & Research PET/MR Center, Nemours/Alfred I. DuPont Hospital for Children, Wilmington, DE, 19803, USA.
Mol Imaging Biol. 2019 Dec;21(6):1138-1146. doi: 10.1007/s11307-019-01327-4.
Fluorine-18 labeled tryptophan analog L-1-[F]fluoroethyl-tryptophan (L-1-[F]FETrp) was designed for positron emission tomography (PET) imaging of cancer by dual targeting of the overexpressed amino acid transporters and altered indoleamine 2,3-dioxygenase (IDO)-mediated kynurenine pathway of tryptophan metabolism. In our previous study, we described the radiosynthesis and preliminary evaluation of L-1-[F]FETrp for PET imaging of breast cancer. The aim of this study was to investigate the in vivo imaging mechanism and further evaluate this radiotracer in more wide range types of cancers including prostate cancer, lung cancer, and glioma.
The mice bearing subcutaneous PC-3 prostate cancer, subcutaneous H2009 and H460 lung cancers, subcutaneous MDA-MB-231, orthotopic A549 lung cancer, and intracranial 73C glioma were employed to evaluate L-1-[F]FETrp for PET imaging of cancer. The in vivo catabolism of L-1-[F]FETrp in the tumor was studied by analysis of PC-3 extracts with radio-HPLC.
Small animal PET/CT imaging of L-1-[F]FETrp visualized all tumors in these different mouse models with high accumulations of radioactivity in PC-3 (7.5 ± 0.6 % ID/g), H2009 (5.3 ± 0.8 % ID/g), H460 (9.0 ± 1.4 % ID/g), A549 (4.5 ± 0.5 % ID/g), and 73C (4.1 ± 0.7 % ID/g) tumors. The radio-HPLC analysis of PC-3 tumor extracts revealed that about 30 % of L-1-[F]FETrp was converted into a highly polar radioactive metabolite. The uptake in H460 cancer was about 1.7-fold higher than that in H2009 cancer, which indicated L-1-[F]FETrp could differentiate these subtypes of lung cancers (H2009 and H460) by imaging quantification. Furthermore, small animal PET/CT imaging in intracranial glioma revealed L-1-[F]FETrp could pass blood-brain barrier (BBB) and accumulate in glioma with a favorable imaging contrast (tumor-to-brain 2.9).
L-1-[F]FETrp highly accumulated in a wide range of malignancies including lung cancer, prostate cancer, and glioma. These results suggested that L-1-[F]FETrp is a promising radiotracer for PET imaging of cancer.
氟-18 标记色氨酸类似物 L-1-[F]氟乙基-色氨酸（L-1-[F]FETrp）旨在通过双重靶向过表达的氨基酸转运体和改变色氨酸代谢中的吲哚胺 2,3-双加氧酶（IDO）介导的犬尿氨酸途径，用于癌症的正电子发射断层扫描（PET）成像。在我们之前的研究中，我们描述了 L-1-[F]FETrp 的放射合成及其用于乳腺癌 PET 成像的初步评估。本研究的目的是研究体内成像机制，并进一步评估该示踪剂在更广泛类型的癌症中的应用，包括前列腺癌、肺癌和脑胶质瘤。
采用皮下接种 PC-3 前列腺癌、皮下接种 H2009 和 H460 肺癌、皮下接种 MDA-MB-231、原位接种 A549 肺癌和颅内接种 73C 脑胶质瘤的小鼠，评估 L-1-[F]FETrp 对癌症的 PET 成像。通过分析 PC-3 提取物的放射性高效液相色谱（radio-HPLC）研究 L-1-[F]FETrp 在肿瘤中的体内代谢情况。
L-1-[F]FETrp 的小动物 PET/CT 成像可视化了这些不同小鼠模型中的所有肿瘤，在 PC-3（7.5±0.6%ID/g）、H2009（5.3±0.8%ID/g）、H460（9.0±1.4%ID/g）、A549（4.5±0.5%ID/g）和 73C（4.1±0.7%ID/g）肿瘤中放射性活性的高积累。PC-3 肿瘤提取物的 radio-HPLC 分析表明，约 30%的 L-1-[F]FETrp 转化为高度极性的放射性代谢物。H460 癌症的摄取量比 H2009 癌症高约 1.7 倍，这表明 L-1-[F]FETrp 可以通过成像定量区分这些肺癌亚型（H2009 和 H460）。此外，颅内脑胶质瘤的小动物 PET/CT 成像显示，L-1-[F]FETrp 可以穿过血脑屏障（BBB）并在脑胶质瘤中积累，具有良好的成像对比度（肿瘤与脑 2.9）。
L-1-[F]FETrp 在包括肺癌、前列腺癌和脑胶质瘤在内的广泛恶性肿瘤中高度积累。这些结果表明，L-1-[F]FETrp 是一种有前途的用于癌症 PET 成像的示踪剂。
