Evaluation of L-1-[¹⁸F]Fluoroethyl-Tryptophan for PET Imaging of Cancer

Objectives: Tryptophan crosses cancer cells through amino acid transporters, and further undergoes catabolism mainly through intracellular IDO/TDO (indoleamine 2,3-dioxygenase/tryptophan 2,3-dioxygenase)-mediated kynurenine pathway, which regulates immune response by suppressing T cell function and allow tumor immune escape. Overexpressed amino acid transporters and altered IDO-mediated kynurenine pathway found in multiple cancers, serve as valid targets for cancer imaging and therapy. Recently, we have reported the radiosynthesis and preliminary evaluation of L-1-[18F]fluoroethyl-tryptophan (L-1-[18F]FETrp) for PET imaging of IDO-mediated kynurenine pathway in breast cancer xenografts.1 In the present study, we described the further evaluation of L-1-[18F]FETrp as an imaging agent in more wide range types of tumor models.

Methods: Radiotracer L-1-[¹⁸F]FETrp was prepared following our previously reported

Methods: ¹ The mice bearing subcutaneous H2009 and H460 lung cancers, orthotopic A549 lung cancer, subcutaneous PC-3 prostate cancer, and intracranial 73C glioma tumor xenografts, were used in L-1-[¹⁸F]FETrp PET imaging. Each mouse was injected with 100-150 μCi of L-1-[¹⁸F]FETrp in saline via the tail vein. PET images were acquired at 2 h post-injection on a Siemens Inveon PET-CT multimodality system.

Results: Small animal PET/CT imaging of L-1-[¹⁸F]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 (Fig. 1). The radiotracer uptakes in lung cancers H2009 and H460 were higher than these in normal lung tissue (1.6 ± 0.1 % ID/g), which also presented in orthotopic A549 lung cancer. The uptake in H460 was about 1.7-fold than that in H2009. These results suggest that L-1-[¹⁸F]FETrp not only enables to detect multiple lung cancers, but also can differentiate the subtype H2009 and H460 cancers by imaging quantification. Furthermore, the PET/CT imaging of intracranial brain tumor revealed L-1-[¹⁸F]FETrp could pass BBB (blood brain barrier) and accumulated in brain tumor with favorable image contrast (tumor/brain: 2.9).

Conclusions: L-1-[18F]FETrp highly accumulates in a wide range of malignancies including lung cancer, prostate cancer, and brain tumor. These PET imaging results suggested that L-1-[18F]FETrp is a promising radiotracer for cancer imaging. Research Support:This work was supported by the Simmons Cancer Center Grant (NIH 5P30 CA 142543), and American Cancer Society and the Simmons Cancer Center (ACS-IRG-02-196).Reference: Xin, Y. & Cai, H. Improved Radiosynthesis and Biological Evaluations of L- and D-1-[18F]Fluoroethyl-Tryptophan for PET Imaging of IDO-Mediated Kynurenine Pathway of Tryptophan Metabolism. Mol. Imaging Biol.19, 589-598 (2017).

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