radiosynthesis-1-2-18ffluoroethyl-l-tryptophan-using-one-pot-two-step

Radiosynthesis of 1-(2-[<sup>18</sup>F]Fluoroethyl)-L-Tryptophan using a One-pot, Two-step Protocol

The kynurenine pathway (KP) is a primary route for tryptophan metabolism. Evidence strongly suggests that metabolites of the KP play a vital role in tumor ...

Nemours/Alfred I. duPont Hospital for Children

N-Methyl-d-aspartate (NMDA) receptors are ligand and voltage-gated heteromeric ion channel receptors. Excessive activation of NMDA receptors is implicated in many neurological and psychiatric disorders, including ischemic stroke, neuropathic pain, epilepsy, drug addition, Alzheimer's disease, and schizophrenia. [F]GE179 is a promising PET probe for imaging functional NMDA receptor alterations (activated or 'open' channel) with a high binding affinity (K = 2.4 nM). Here, we report the production of the NMDA receptor radioligand [F]GE179 in a current Good Manufacturing Practice (cGMP) facility through a one-pot two-step strategy. [F]GE179 was produced in approximately 110 min with a radiochemical yield of 12 ± 6% (n = 4, decay corrected), radiochemical purity >95%, molar activity of 146 ± 32 GBq/μmol (at the end of synthesis), an average mass of GE179 at 2.2 μg/batch, and total impurities less than 0.5 μg/batch (n = 4). The radiopharmaceutical dose meets all quality control (QC) criteria for human use, and is suitable for clinical PET studies of activated NMDA receptor ion channels.

Automated production of a N-methyl-D-aspartate receptor radioligand [F]GE179 for clinical use.

Automated production of an fluorine-18 labeled tryptophan analogue, 1-(2-[F]fluoroethyl)-l-tryptophan (1-L-[F]FETrp) in a current Good Manufacturing Practice facility was achieved. 1-L-[F]FETrp was produced by a one-pot, two-step strategy with an overall synthesis time of approximately 100 min, a radiochemical yield of 20 ± 5% (decay corrected), radiochemical purity and enantiomeric excess over 90%, and a molar activity of 103 ± 15 GBq/μmol at the end of synthesis (EOS). The dose mass of 1-L-FETrp in four consecutive batches was less than 5 μg. The radiopharmaceutical product met all quality control criteria for clinical use.

Automated production of 1-(2-[F]fluoroethyl)-l-tryptophan for imaging of tryptophan metabolism.

In vivo positron emission tomography (PET) imaging is a key modality to evaluate disease status of brain tumors. In recent years, tremendous efforts have been made in developing PET imaging methods for pediatric brain tumors. Carbon-11 labelled tryptophan derivatives are feasible as PET imaging probes in brain tumor patients with activation of the kynurenine pathway, but the short half-life of carbon-11 limits its application. Using a transgenic mouse model for the sonic hedgehog (Shh) subgroup of medulloblastoma, here we evaluated the potential of the newly developed 1-(2-[F]fluoroethyl)-L-tryptophan (1-L-[F]FETrp) as a PET imaging probe for this common malignant pediatric brain tumor. 1-L-[F]FETrp was synthesized on a PETCHEM automatic synthesizer with good chemical and radiochemical purities and enantiomeric excess values. Imaging was performed in tumor-bearing Smo/Smo medulloblastoma mice with constitutive actvation of the Smoothened (Smo) receptor using a PerkinElmer G4 PET-X-Ray scanner. Medulloblastoma showed significant and specific accumulation of 1-L-[F]FETrp. 1-L-[F]FETrp also showed significantly higher tumor uptake than its D-enantiomer, 1-D-[F]FETrp. The uptake of 1-L-[F]FETrp in the normal brain tissue was low, suggesting that 1-L-[F]FETrp may prove a valuable PET imaging probe for the Shh subgroup of medulloblastoma and possibly other pediatric and adult brain tumors.

PET imaging of medulloblastoma with an F-labeled tryptophan analogue in a transgenic mouse model.

Birth trauma accounts for 1-2% of the mortality in newborns with significant intracranial injuries presenting in the immediate postnatal period. However, a significant number of asymptomatic neonates harbor birth-related intracranial hemorrhage (ICH), with birth-related subdural hemorrhage (SDH) being a common occurrence on infant brain CT and MRI studies performed as a standard of care for a variety of reasons. Although clinically insignificant, birth-related SDH is frequently brought up in courts as an alternative explanation for SDH in suspected abusive head trauma.

Article	Year
Automated production of a N-methyl-D-aspartate receptor radioligand [F]GE179 for clinical use. Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine\| PubMed ID: 31026789	2019
Automated production of 1-(2-[F]fluoroethyl)-l-tryptophan for imaging of tryptophan metabolism. Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine\| PubMed ID: 32056678	2020
PET imaging of medulloblastoma with an F-labeled tryptophan analogue in a transgenic mouse model. Scientific reports\| PubMed ID: 32123231	2020
Birth-related subdural hemorrhage: prevalence and imaging morphology. Pediatric radiology\| PubMed ID: 33830289	2021

Xuyi Yue

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