HYPOXFLU · [18F]Fluorination of alkylCF3 and alkylCF2CF3 chains-Application to hypoxia biomarkers for PET imaging.

[18F]Fluorination of alkylCF3 and alkylCF2CF3 chains-Application to hypoxia biomarkers for PET imaging.

Hypoxia is the pathological condition of insufficient oxygen supply, characteristic of advanced solid tumors, usually resulting in a resistance to radiation- and chemotherapy and consequently a negative prognostic factor for patients. A number of methods to measure hypoxia exist, however, as tumors are highly heterogeneous, 3D imaging methods as PET imaging for example, are still crucial. 18F-based Positron Emission Tomography (PET) imaging is a non-invasive and sensitive in-vivo imaging modality that can provide quantitative measurements of biological processes, allowing clinicians to make an accurate diagnosis and prognosis and so to provide an effective personalized treatment region, increasing a patient’s quality of life. However, progress in this field is currently hindered by the lack of methods that allow the rapid and efficient late-stage introduction of 18F into targets of interest. Among the known biomarkers for the detection of hypoxia, [18F]FMISO has been studied extensively, both preclinically and clinically, in different cancer types. Despite being the most widely used PET agent for regional hypoxia mapping, concerns have been raised about the use of [18F]FMISO. EF5 and EF3 are second-generation biomarkers, and their potential advantages over other hypoxia biomarkers is well documented. However, the use of their 18F counterparts for PET imaging is sparse, due to a fundamental lack of suitable radiochemical transformations. Therefore, the development of novel, efficient methods to reach these motives would not only facilitate widespread research into [18F]EF5 and [18F]EF3, but also the use of alkyl [18F]CF3 or [18F]CF2CF3 motifs more generally in the design of radiotracers, as a number of therapeutic agents and/or biomarkers containing perfluorinated chains are described in the literature. The overall objectives of this project are 1) to develop a novel methodology for the labelling of alkyl-CF3 and alkyl-CF2CF3 chains, 2) to develop an automated radiolabelled synthesis of tumor hypoxia biomarkers [18F]EF3 and [18F]EF5 as a proof of concept, and 3) to perform an in-vivo pre-clinical comparative study of the properties of [18F]FMISO, [18F]EF3 and [18F]EF5 for imaging hypoxia in small animals.

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