[¹⁸F]FPyKYNE, a fluoropyridine‐based alkyne reagent designed for the fluorine‐18 labelling of macromolecules using click chemistry

Abstract

FPyKYNE (2‐fluoro‐3‐pent‐4‐yn‐1‐yloxypyridine) is a novel fluoropyridine‐based structure, designed for the fluorine‐18 labelling of macromolecules using copper‐catalysed Huisgen 1,3‐dipolar cycloaddition (click chemistry). FPyKYNE (non‐labelled as reference), as well as the 2‐bromo, 2‐nitro and 2‐trimethylammonium analogues (as precursors for labelling with fluorine‐18), was synthesized in 44, 95, 60 and 41%, respectively, from commercially available 5‐chloropent‐1‐yne and the appropriate 2‐substituted‐3‐hydroxypyridines. [18F]FPyKYNE was synthesized in one single radiochemical step by reaction of no‐carrier‐added K[18F]F‐Kryptofix®222 (DMSO, 165°C, 3–5 min) followed by C‐18 SepPak cartridge pre‐purification and finally semi‐preparative HPLC purification on a Hewlett Packard SiO2 Zorbax® Rx‐SIL. Using the 2‐nitropyridine or the pyridin‐2‐yltrimethylammonium trifluoromethanesulphonate precursor for labelling (30 and 10 µmol, respectively), incorporation yields up to 90% were observed and 7.0–8.9 GBq (190–240 mCi) of [18F]FPyKYNE ([18F]‐1) could be isolated within 60–70 min (HPLC purification included), starting from a 37.0 GBq (1.0 Ci) [18F]fluoride batch (overall decay‐corrected and isolated yields: 30–35%). Copyright © 2008 John Wiley & Sons, Ltd.

Development and Evaluation of Endothelin-A Receptor (Radio)Ligands for Positron Emission Tomography

“…Sodium 2-benzo [1,3]dioxol-5-yl-4-(4-methoxyphenyl)-4-oxo-3-(3,4,5-trimethoxybenzyl)but-2-enoate, 32 43 The analytical data correspond to literature data. 54 55 using a procedure similar to that described by Kuhnast et al 56 All animal experiments were conducted in accordance with local institutional guidelines for the care and use of laboratory animals.…”

[18F]FPyZIDE: A versatile prosthetic reagent for the fluorine‐18 radiolabeling of biologics via copper‐catalyzed or strain‐promoted alkyne‐azide cycloadditions

“…These yields are comparable with those obtained for the preparation of other [ 18 F]pyridine-based prosthetic reagents. [ 18 F]FPyKYNE was prepared in 30% to 35% decay-corrected yield in 60 to 70 minutes, 45 46,47 Only the analog 18 F-BMT-187144 was prepared in a surprisingly high 70% non-decay-corrected yield. 42 The chemical and radiochemical purities were greater than 95% and 99%, respectively, as assessed by the quality control.…”

“…Their preparation thus requires multistep processes that are limiting regarding the half-life of fluorine-18 and the automation access. Consequently, many alkyne-or azidecontaining tags have flourished in the literature displaying [ 7,22,23,[36][37][38][39][40][41][42] On the basis of our experience in the preparation of [ 18 F]fluoropyridine-based prosthetic reagents [43][44][45] and analogously to already developed clickable ones, 42,46,47 we report the preparation of a novel azide-containing prosthetic reagent ([ 18 F]FPyZIDE). Its versatility in cycloaddition reactions has been illustrated using a propargylated cysteine derivative and two cyclooctyne models.…”

A review of approaches to 18F radiolabelling affinity peptides and proteins

“…The ease with which pyridine can be fluorinated at both the C2 and C4 positions, attributable to the presence of the nitrogen "electron-sink", has led to an increasing number of pyridine-based prosthetic groups. 44,50,51 One such example is [ 18 F]FPCA, a water-soluble 18 F prosthetic group developed by Morris et al 44 Its radiosynthesis has been fully automated using a customised GE Tracerlab FX-FN with [ 18 F]FPCA RCY of 28 ± 2% (d.c., n = 10) reported. 44 Morris et al 44 [ 18 F]SFB, similarly to [ 18 F]FPCA, radiolabels APPs through conjugation with the inherent nucleophilic sites of the APP.…”