Automated radiosynthesis of 1‐(2‐[¹⁸F]fluoroethyl)‐L‐tryptophan ([¹⁸F]FETrp) for positron emission tomography (PET) imaging of cancer in humans

Abstract

The radiotracer 1-(2-[ 18 F]fluoroethyl)-L-tryptophan (L-[ 18 F]FETrp or [ 18 F] FETrp) is a substrate of indoleamine 2,3-dioxygenase, the initial and key enzyme of the kynurenine pathway associated with tumoral immune resistance. In preclinical positron emission tomography studies, [ 18 F]FETrp is highly accumulated in a wide range of primary and metastatic cancers, such as lung cancer, prostate cancer, and gliomas. However, the clinical translation of this radiotracer into the first-in-human trial has not been reported, partially due to its racemization during radiofluorination which renders the purification of the final product challenging. However, efficient purification is essential for human studies in order to assure radiochemical and enantiomeric purity. In this work, we report a fully automated radiosynthesis of [ 18 F]FETrp on a Synthra RNPlus research module, including a one-pot two steps radiosynthesis, dual independent chiral and reverse-phase semipreparative high-performance liquid chromatography purifications, and solid-phase extraction-assisted formulation. The presented approach has led to its Investigational New Drug application and approval that allows the testing of this tracer in humans.

The First Human Application of an F-18-labeled Tryptophan Analog for PET Imaging of Cancer

“…Radioligand preparation. 18 F-FETrp was prepared as described recently [17] and was carried as outlined in our FDA-approved Investigational New Drug Application (#162,122). 18 F-FETrp was obtained with high radiochemical purity (> 99%) and had speci c radioactivity of 226 ± 19 GBq/µmol (N = 6 batches) at the time of injection.…”