Recent Developments in the Chemistry of [¹⁸F]Fluoride for PET

A novel versatile precursor suitable for 18F‐radiolabeling via “click chemistry”

“…The obtained crude product 13 (1.45 g, 3.66 mmol, 99% yield) was employed in the following step without further purifications. R f 0.82.Proton nuclear magnetic resonance δ 1.46 to 1.92 (m, 6H, 3CH 2 ), 2.07 (s, 3H, CH 3 CO), 3…”

“…The strength of the C─F bond (105.4 kcal mol −1 ) exceeds that of C─H bond (98.8 kcal mol −1 ) and of C─O bond (84.0 kcal mol −1 ), and for this reason, fluorine is often used to replace hydrogen in medicinal chemistry. [1][2][3] In the last decade, there has been increasing interest in the 18 F radiolabeling of biomolecules such as peptides, proteins, nucleic acids, and oligomers. As direct 18 F radiolabeling of the above biomolecules is usually not feasible, due to both the lack of functional groups suitable for direct nucleophilic substitution and harsh conditions often used during this reaction type, a variety of indirect methods were developed, the most common of which has long been the radiofluorination of small molecules to achieve a prosthetic group, which is then conjugated to the biomolecule under mild conditions.…”

“…As direct 18 F radiolabeling of the above biomolecules is usually not feasible, due to both the lack of functional groups suitable for direct nucleophilic substitution and harsh conditions often used during this reaction type, a variety of indirect methods were developed, the most common of which has long been the radiofluorination of small molecules to achieve a prosthetic group, which is then conjugated to the biomolecule under mild conditions. [3][4][5][6] To this regard, the Cu(I)-catalyzed Huisgen [3 + 2] cycloaddition between terminal alkynes and azides, the so-called copper-catalyzed azide alkyne cycloaddition (CuAAC), was widely used in recent years because of its regioselectivity, mild aqueous organic conditions, reduced reaction times, and high yields. Moreover, the produced 1,2,3-triazoles usually show biological stability and polarity and size similar to amide or peptide bonds.…”

“…Finally, as alkynes and azides are inert toward classic biomolecule functionalities, there is no need for protection strategy during CuAAC. 3,4 Therefore, a new class of precursors for the 18 F radiolabeling of biomolecules such as amino acids, peptides, and oligomers was developed. 7 As CuAAC is alkyne-rate dependent, 8,9 our attention was focused on azido precursor, the best strategy to save time and resources being the 18 F radiolabeling of such a precursor and the subsequent cycloaddition with an alkynyl-modified biomolecule.…”

18F-labelling innovations and their potential for clinical application

“…A plethora of recent reviews already summarizes the major progress achieved, e.g. for the late-stage 18 F-fluorination of aromatic and heteroaromatic compounds [1,2], the use of prosthetic groups and building blocks [3][4][5], asymmetric 18 F-fluorination [6], bond formation of fluorine-18 with group 13 and 14 elements [7][8][9][10], as well as general and technical aspects [11,12]. Since n.c.a.…”