technical-aspect-automated-synthesis-real-time-kinetic-evaluation

Technical Aspect of the Automated Synthesis and Real-Time Kinetic Evaluation of [<sup>11</sup>C]SNAP-7941

Positron emission tomography (PET) is an essential molecular imaging technique providing insights into pathways and using specific targeted radioligands ...

Medical University of Vienna

The tracer -Hydroxyephedrine ([[11C]HED) is one of the most applied PET tracers for cardiac imaging, whose radiosynthesis was already reported in 1990. While not stated in the literature, separation difficulties and an adequate formulation of the product are well known challenges in its production. Furthermore, the precursor (metaraminol) is also a substrate for the norepinephrine transporter, and can therefore affect the image quality. This study aims at optimizing the synthetic process of [[11C]HED and investigating the effect of the apparent molar activity (sum of HED and metaraminol) in patients and animals. The main optimization was the improved separation through reverse phase-HPLC by a step gradient and subsequent retention of the product on a weakly-cationic ion exchange cartridge. The µPET/µCT was conducted in ten rats (ischemic model) and the apparent molar activity was correlated to the VOI- and SUV-ratio of the myocardium/intra-ventricular blood pool. Moreover, nine long-term heart transplanted and five Morbus Fabry patients underwent PET and MRI imaging for detection of changes in the sympathetic innervation. In summary, the fully-automated synthesis and optimized purification method of [[11C]HED is easily applicable and reproducible. Moreover, it was shown that the administered apparent molar activities had a negligible effect on the imaging quality.

Optimization of the Automated Synthesis of [11C]mHED-Administered and Apparent Molar Activities.

An intriguing target involved in several pathophysiological processes is the 18 kDa translocator protein (TSPO), of which exact functions remained elusive until now. A single nucleotide polymorphism in the  gene influences the binding affinity of endogenous and synthetic TSPO ligands by facilitating a lower-affinity conformation, which modifies a potential ligand binding site, ultimately leading to a binding profile classification according to each genotype. For instance, some clinical effects of the distinctive binding affinity profile of cholesterol toward the TSPO of individuals with different genotypes have been extensively discussed. Therefore, we conducted an investigation based on a radioligand binding assay, to determine the inhibition constants of some reported endogenous TSPO ligands (diazepam binding inhibitor and protoporphyrin IX), as well as synthetic ligands (disulfiram and derivatives). We observed no dependency of the polymorphism on the binding affinity of the evaluated endogenous ligands, whereas a high dependency on the binding affinity of the tested synthetic ligands was evident.

Binding Affinity of Some Endogenous and Synthetic TSPO Ligands Regarding the rs6971 Polymorphism.

Type 4 chemokine receptor (CXCR4) plays an important role in immune cell migration during the atherosclerosis progression. We aimed to evaluate [Ga]Pentixafor positron emission tomography (PET) in combination magnetic resonance imaging (MRI) for in vivo quantification of CXCR4 expression in carotid plaques.

Article	Year
Optimization of the Automated Synthesis of [11C]mHED-Administered and Apparent Molar Activities. Pharmaceuticals (Basel, Switzerland)\| PubMed ID: 30646635	2019
Binding Affinity of Some Endogenous and Synthetic TSPO Ligands Regarding the rs6971 Polymorphism. International journal of molecular sciences\| PubMed ID: 30699908	2019
[Ga]Pentixafor PET/MR imaging of chemokine receptor 4 expression in the human carotid artery. European journal of nuclear medicine and molecular imaging\| PubMed ID: 31004184	2019

Marcus Hacker

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