Reaction of [18F]Fluoride at Heteroatoms and Metals for Imaging of Peptides and Proteins by Positron Emission Tomography

Abstract

The ability to radiolabel proteins with [18F]fluoride enables the use of positron emission tomography (PET) for the early detection, staging and diagnosis of disease. The direct fluorination of native proteins through C-F bond formation is, however, a difficult task. The aqueous environments required by proteins severely hampers fluorination yields while the dry, organic solvents that promote nucleophilic fluorination can denature proteins. To circumvent these issues, indirect fluorination methods making use of prosthetic groups that are first fluorinated and then conjugated to a protein have become commonplace. But, when it comes to the radiofluorination of proteins, these indirect methods are not always suited to the short half-life of the fluorine-18 radionuclide (110 min). This review explores radiofluorination through bond formation with fluoride at boron, metal complexes, silicon, phosphorus and sulfur. The potential for these techniques to be used for the direct, aqueous radiolabeling of proteins with [18F]fluoride is discussed.

Hetero-Diels–Alder click reaction of dithioesters for a catalyst-free indirect 18F-radiolabelling of peptides

“…Hence, the interest in peptide radiolabelling has grown considerably over the past few years, as demonstrated by numerous reviews devoted to this topic. 1,2 Fluorine-18, the most used radionuclide in the positron emission tomography (PET) imaging technique, is characterized by a half-life ( t 1/2 ) of 109.8 min, thus matching the pharmacokinetics of peptides and explaining its successful use in this field. 2 18 F-labelling can be achieved through direct or indirect approaches, however mild reaction conditions are required when a peptide is involved.…”

“…1,2 Fluorine-18, the most used radionuclide in the positron emission tomography (PET) imaging technique, is characterized by a half-life ( t 1/2 ) of 109.8 min, thus matching the pharmacokinetics of peptides and explaining its successful use in this field. 2 18 F-labelling can be achieved through direct or indirect approaches, however mild reaction conditions are required when a peptide is involved. Despite the interest and the advances in the direct radiofluorination of peptides, 3 indirect approaches remain the most used.…”

PET Molecular Imaging in Drug Development: The Imaging and Chemistry Perspective

“…The 18 F fluoride acts as a nucleophile, hence it is used in nucleophilic substitution reactions, whereas [ 18 F]F 2 fluorine acts as an electrophile, hence it is used in electrophilic substitution reactions (49). Recent advances have come to produce 18 F-radiopharmaceuticals through transitional metalmediated reactions and prosthetic groups involved reactions for 18F-labeled peptides, and proteins (50).…”

Radiofluorination Methods: Historical Overview and Current State

“…Известно, что арилбороновые кислоты могут быть фторированы с помощью KHF 2 в кислой среде с получением арилтрифторборатных солей с высоким выходом. Эта особенность позволяет проводить реакции водного 18 F-фторирования борорганических кислот и их сложных эфиров [54].…”