Synthetic α-Conotoxin Mutants as Probes for Studying Nicotinic Acetylcholine Receptors and in the Development of Novel Drug Leads

α-Conotoxins are peptide neurotoxins isolated from venomous marine cone snails that are potent and selective antagonists for different subtypes of nicotinic acetylcholine receptors (nAChRs). As such, they are valuable probes for dissecting the role that nAChRs play in nervous system function. In recent years, extensive insight into the binding mechanisms of α-conotoxins with nAChRs at the molecular level has aided in the design of synthetic analogs with improved pharmacological properties. This review examines the structure-activity relationship studies involving α-conotoxins as research tools for studying nAChRs in the central and peripheral nervous systems and their use towards the development of novel therapeutics

Fully Automated GMP-Compliant Synthesis of [18F]FE-PE2I

In the struggle to understand and accurately diagnose Parkinson′s disease, radiopharmaceuticals and medical imaging techniques have played a major role. By being able to image and quantify the dopamine transporter density, noninvasive diagnostic imaging has become the gold standard. In the shift from the first generation of SPECT tracers, the fluorine-18-labeled tracer [18F]FE-PE2I has emerged as the agent of choice for many physicians. However, implementing suitable synthesis for the production of [18F]FE-PE2I has proved more challenging than expected. Through a thorough analysis of the relevant factors affecting the final radiochemical yield, we were able to implement high-yielding fully automated GMP-compliant synthesis of [18F]FE-PE2I on a Synthera®+ platform. By reaching RCYs up to 62%, it allowed us to isolate 25 GBq of the formulated product, and an optimized formulation resulted in the shelf life of 6 h, satisfying the increased demand for this radiopharmaceutical.</jats:p

Fully Automated GMP-Compliant Synthesis of [¹⁸F]FE-PE2I

In the struggle to understand and accurately diagnose Parkinson′s disease, radiopharmaceuticals and medical imaging techniques have played a major role. By being able to image and quantify the dopamine transporter density, noninvasive diagnostic imaging has become the gold standard. In the shift from the first generation of SPECT tracers, the fluorine-18-labeled tracer [(18)F]FE-PE2I has emerged as the agent of choice for many physicians. However, implementing suitable synthesis for the production of [(18)F]FE-PE2I has proved more challenging than expected. Through a thorough analysis of the relevant factors affecting the final radiochemical yield, we were able to implement high-yielding fully automated GMP-compliant synthesis of [(18)F]FE-PE2I on a Synthera(®)+ platform. By reaching RCYs up to 62%, it allowed us to isolate 25 GBq of the formulated product, and an optimized formulation resulted in the shelf life of 6 h, satisfying the increased demand for this radiopharmaceutical

[¹⁸F]FE-PE2I PET is a feasible alternative to [¹²³I]FP-CIT SPECT for dopamine transporter imaging in clinically uncertain parkinsonism

BACKGROUND: Dopamine transporter (DAT) imaging of striatum is clinically used in Parkinson’s disease (PD) and neurodegenerative parkinsonian syndromes (PS) especially in the early disease stages. The aim of the present study was to evaluate the diagnostic performance of the recently developed tracer for DAT imaging [(18)F]FE-PE2I PET/CT to the reference standard [(123)I]FP-CIT SPECT. METHODS: Ninety-eight unselected patients referred for DAT imaging were included prospectively and consecutively and evaluated with [(18)F]FE-PE2I PET/CT and [(123)I]FP-CIT SPECT on two separate days. PET and SPECT scans were categorized independently by two blinded expert readers as either normal, vascular changes, or mixed. Semiquantitative values were obtained for each modality and compared regarding effect size using Glass’ delta. RESULTS: Fifty-six of the [(123)I]FP-CIT SPECT scans were considered abnormal (52 caused by PS, 4 by infarctions). Using [(18)F]FE-PE2I PET/CT, 95 of the 98 patients were categorized identically to SPECT as PS or non-PS with a sensitivity of 0.94 [0.84–0.99] and a specificity of 1.00 [0.92–1.00]. Inter-reader agreement for [(18)F]FE-PE2I PET with a kappa of 0.97 [0.89–1.00] was comparable to the agreement for [(123)I]FP-CIT SPECT of 0.96 [0.76–1.00]. Semiquantitative values for short 10-min reconstructions of [(18)F]FE-PE2I PET/CT were comparable to longer reconstructions. The effect size for putamen/caudate nucleus ratio was significantly increased using PET compared to SPECT. CONCLUSIONS: The high correspondence of [(18)F]FE-PE2I PET compared to reference standard [(123)I]FP-CIT SPECT establishes [(18)F]FE-PE2I PET as a feasible PET tracer for clinical use with favourable scan logistics. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13550-022-00930-x