Littérature scientifique sur le sujet « F-18 radiolabelling »

The fluorine-18 radiolabelled octreotide [¹⁸F]FET-βAG-TOCA has been evaluated clinically for positron emission tomography (PET) imaging of neuroendocrine tumours (NETs). An improved automated radiosynthesis using “click” chemistry (CuAAC) and the 2-[¹⁸F]fluoroethylazide prosthetic group is reported and with minimal adaptation, may be used for radiolabelling other peptides.

The fluorinase enzyme is used to catalyse transhalogenation reactions on dendritic RGD peptide constructs. The strategy is explored for [¹⁸F]-radiolabelling of peptides under neutral aqueous ambient conditions for positron emission tomography (PET).

A series of 1^st row transition metal trifluoride complexes with neutral N₃-donor ligands is described; radiolabelling of [FeF₃(BnMe₂-tacn); in aqueous MeCN is achieved by ¹⁸F/¹⁹F isotopic exchange and its stability in PBS and serum established.

Radiopharmaceuticals targeting the prostate-specific membrane antigen (PSMA) has become the gold standard for PET imaging of prostate cancer. [68Ga]Ga-PSMA-11 has been the forerunner but a [18F]F-PSMA ligand has been developed because of the intrinsic advantages of Fluorine-18. Fluorine-18 labelled compounds are usually prepared in centers with an on-site cyclotron. Since our center has not an on-site cyclotron, we decided to verify the feasibility of producing the experimental 18F-labelled radiopharmaceutical [18F]F-PSMA-1007 with [18F]F- from different external suppliers. A quality agreement has been signed with two different suppliers, and a well-established and correctly implemented quality assurance protocol has been followed. The [18F]F- was produced with cyclotrons, on Nb target, but with different beam energy and current. Extensive validation of the [18F]F-PSMA-1007 synthesis process has been performed. The aim of this paper was the description of all the quality documentation which allowed the submission and approval of the Investigational Medicinal Product Dossier (IMPD) to the Competent Authority, addressing the quality problems due to different external suppliers. The result indicates that no significant differences have been found between the [18F]F- from the two suppliers in terms of radionuclidic and radiochemical purity and [18F]F- impacted neither the radiochemical yield of the labelling reaction nor the quality control parameters of the IMP [18F]F-PSMA-1007. These results prove how a correct quality assurance system can overcome some Regulatory Authorities issue that may represent an obstacle to the clinical use of F-18-labelled radiopharmaceuticals without an on-site cyclotron.

A new prosthetic group is reported for quantitative ¹⁸F-labelling of peptides and proteins based on the chemoselective ligation of potassium acyltrifluoroborates (KATs) and hydroxylamines without any detectable ¹⁸F/¹⁹F isotope exchange at the KAT moiety.

The doctorate project is focused on the development and standardization of a general method for F-18 radiolabelling of biologically interesting molecules (e.g. peptides and oligomers), to carry out in vivo imaging assays by PET (Positron Emission Tomography). The selected procedure deals with the introduction of a terminal alkynyl group into the biological substrate, and the synthesis of a functionalizable F-18 molecule containing an azide moiety. Once introduced the radioisotope, the following Huisgen dipolar cycloaddition between the alkyne and the azide affords the desired radiolabelled biomolecule. After problematic and non-producing attempts in employing commercial available or described azides, a fully new fluorinated azide was designed. It is composed by a bifunctionalized aryl bringing, not directly linked to the ring, an azide group at one side, and a PEG chain terminated by a fluoride atom at the other. The aim is to obtain a precursor with suitable characteristics of versatility, easy handling, stability, and reactivity, necessary to make efficient conjugation to biomolecules, and to minimize non-specific binding during PET exam. The synthetic work was carried-out in BIOMETRA Department labs of Milan University, in collaboration with the professor Patrizia Ferraboschi research group, while the radiochemistry activities were performed in Tecnomed Foundation (Milano-Bicocca University) labs. Various synthetic pathways were tested in order to obtain an azidic precursor useful for F-18 introduction, and for the subsequent cycloaddition reaction. In particular, a strategy of consecutive orthogonal protection-deprotection steps brought to the synthesis of three different precursor types (tosylate, mesylate, and iodinated), and the fluorinated reference standard. Starting from commercially available methyl 4-(bromomethyl)benzoate, the ester group was reduced to alcohol. The alcohol residue was protected as tetrahydropyranyl ether, while bromine was employed as leaving group to introduce a triethylene glycol chain. After protection of the terminal hydroxyl as acetate, benzylic hydroxyl was transformed to mesylate, and finally to azide. Removal of the acetate made possible the introduction of the mentioned leaving groups useful for the fluorination reaction. F-18 radiolabelling tests, carried-out on a dedicated automated synthesis module, demonstrated that the best precursor, in terms of radiolabelling yield and effectiveness of purification by separation to the substrate, was the iodinated one. Purification of radioactive azide through cartridges procedure resulted in 51% radiochemical yield non-corrected for the decay (radiochemical purity 93%). It was then carried-out the fluoroazide conjugation with a low-cost biological model, propargylglycine. The cold click-chemistry reaction was performed in a water/acetonitrile/DMSO solution, in presence of copper (II) sulfate, and sodium ascorbate, bringing successfully to the corresponding 1,2,3-triazole. The radioactive analogue reaction showed the effectiveness of the conversion to the radioactive triazole (52% conversion, non-corrected for the decay) within 30 minutes. In future developments, a resources scale-down for the radioactive procedure will be implemented. Moreover, the triazole final purification method will be optimized, and this methodology will be applied to biologically relevant molecules (e.g. the propargylglycine S-enantiomer or interesting tool-peptides such as RGD or NGR peptides). In vivo imaging will be performed on a dedicated small animal PET scanner, in collaboration with the pre-clinical research group directed by professor Rosamaria Moresco (Milano-Bicocca University).