Evaluation of tryptophan and tyrosine-based newly developed PET tracers in U87 glioma model

Ziel/Aim: The L-type amino acid transporter 1 (LAT1) is overexpressed in gliomas and other brain tumors, making it an attractive target for positron emission tomography (PET) with radiolabeled amino acids. However, while PET imaging with the established tracer O-(2-[F-18]fluoroethyl)-l-tyrosine ([F-18]FET) enables glioma detection with higher specificity and sensitivity than conventional imaging methods, tumor uptake of this probe is limited by a relatively low LAT1 affinity. Therefore, this study aimed to investigate the potential of two alternative radiolabeled amino acid analogs, 7-[F-18]fluoro-l-tryptophan (7-[F-18]FTrp) and 5-[F-18]fluoro-meta-l-tyrosine (5-[F-18]FMT), for brain tumor imaging in an orthotopic glioma model.

Methodik/Methods: 5-[F-18]FMT, [F-18]FET and 7-[F-18]FTrp were synthesized by direct radiofluorination. The orthotopic glioma model was generated by stereotactic implantation of U87 MG cells into the brain of male Rowett Nude rats (n=4). Tumor growth was monitored by T2-weighted MR imaging. PET measurements were performed once the tumors reached a diameter of approximately 4.4 mm, using a Siemens Focus 220 small animal PET scanner and [F-18]FET as the reference tracer.

Ergebnisse/Results: All tracers were synthesized in activity yields of 25–57% and molar activities of 5–170 GBq/µmol. Analysis of the PET images revealed similar tumor accumulation for 7-[F-18]FTrp (max SUVbw=82.1) and [F-18]FET (max SUVbw=79.9), with peak uptake of both tracers at 5 minutes post-injection. In contrast, 5-[F-18]FMT showed higher initial tumor uptake (max SUVbw=90.26) but rapid washout from both tumor and normal brain tissue. Tumor-to-background ratios were comparable across all three tracers.

Schlussfolgerungen/Conclusions: These findings suggest that 7-[F-18]FTrp is a promising PET probe for glioma imaging, comparable to the established tracer [F-18]FET. Conversely, while 5-[F-18]FMT shows higher initial tumor uptake, the lack of sustained tumor retention may limit its utility for glioma imaging.

Publication History

Article published online:
12 March 2025