FASTlab Radiosynthesis of the F-labelled HER2-binding Affibody molecule [ F]GE-226.

An F-labelled human epidermal growth factor receptor (HER2) receptor binding radiotracer is a potential tool to non-invasively identify HER2 positive tumour lesions in subjects with recurrent metastatic breast cancer. Having explored the manual radiochemistry to conjugate the Affibody molecule Z with [ F]4-fluorobenzaldehyde, we have developed and optimised a full protocol for the automated GE FASTlab synthesiser. Our chemometric model predicted the best radiochemical purity for a short conjugation time (2.

Exploration of the impact of stereochemistry on the identification of the novel translocator protein PET imaging agent [(18)F]GE-180.

Introduction: The tricyclic indole compound, [(18)F]GE-180 has been previously identified as a promising positron emission tomography (PET) imaging agent of the translocator protein (TSPO) with the potential to aid in the diagnosis, prognosis and therapy monitoring of degenerative neuroinflammatory conditions such as multiple sclerosis. [(18)F]GE-180 was first identified and evaluated as a racemate, but subsequent evaluations of the resolved enantiomers have shown that the S-enantiomer has a higher affinity for TSPO and an improved in vivo biodistribution performance, in terms of higher uptake in specific brain regions and good clearance (as described previously). Here we describe the additional biological evaluations carried out to confirm the improved performance of the S-enantiomer and including experiments which have demonstrated the stability of the chiral centre to chemical and biological factors.

The development of an automated and GMP compliant FASTlab™ Synthesis of [(18) F]GE-180; a radiotracer for imaging translocator protein (TSPO).

The level of the translocator protein (TSPO) increases dramatically in microglial cells when the cells are activated in response to neuronal injury and insult. The radiotracer [(18) F]GE-180 binds selectively and with high affinity to TSPO and can therefore be used to measure neuroinflammation in a variety of disease states. An optimized, automated synthesis of [(18) F]GE-180 has been developed for the GE FASTlab™ synthesizer.

Exploration of the structure-activity relationship of a novel tetracyclic class of TSPO ligands-potential novel positron emitting tomography imaging agents.

A series of novel TSPO ligands based on the tetracyclic class of translocator protein (TSPO) ligands first described by Okubo et al. was synthesised and evaluated as potential positron emitting tomography (PET) ligands for imaging TPSO in vivo. Fluorine-18 labelling of the molecules was achieved using direct radiolabelling or synthon based labelling approaches.

[¹⁸F]GE-180: a novel fluorine-18 labelled PET tracer for imaging Translocator protein 18 kDa (TSPO).

A series of tricyclic compounds have been synthesised and evaluated in vitro for affinity against Translocator protein 18 kDa (TSPO) and for preferred imaging properties. The most promising of the compounds were radiolabelled and evaluated in vivo to determine biodistribution and specificity for high expressing TSPO regions. Metabolite profiling in brain and plasma was also investigated.