Radiosynthesis of an ¹⁸F‐fluoroglycosylated aminoferrocene for in‐vivo imaging of reactive oxygen species activity by PET

Abstract

The imaging of reactive oxygen species (ROS) at the molecular level with high sensitivity and specificity by positron emission tomography (PET) could be of enormous interest to increase our knowledge about ROS activity and signalling, especially in tumours. The aim of this research was to optimise the click chemistry‐based radiosynthesis of an 18F‐labelled aminoferrocene glycoconjugate that was derived from an N‐alkylaminoferrocene lead structure known to have anticancer activity in vitro. Applying the solvent system phosphate buffer/THF (12/5), Cu(OAc)2 and sodium ascorbate as reducing agent at 60°C, the alkyne 1 reacted with the 18F‐labelled glycosyl azide [18F]2 in the presence of carrier 3 (47μM) to obtain carrier‐added [18F]4 in a radiochemical yield of 85%. Interestingly, the addition of carrier was essential for sufficient radiochemical yield, because it suppressed the oxidation of no‐carrier‐added (n.c.a.) [18F]4. Future work will include the formulation of c.a. [18F]4 for studying its biodistribution in tumour‐bearing mice.

Sweetening Pharmaceutical Radiochemistry by 18F-Fluoroglycosylation: Recent Progress and Future Prospects

“…Noteworthily, the purification of the 18 F-labeled aminoferrocene glycoconjugate was problematic, since the hydrolysis of the boronic acid ester and oxidation of non-carrier-added 26 occurred in the buffered solution. However, the RCY (referred to the CuAAC reaction) of carrier-added 26 was 85% under optimized conditions [55]. Further PET studies in PC3 and AR42J tumor-bearing mice demonstrated that carrier-added 26 showed a 2−3-fold higher tumor uptake at 45-60 min p.i.…”

“…Tracers for imaging the content of reactive oxygen species (ROS) in tumors could be valuable for PET imaging of tumors and contribute to our knowledge of the biodistribution of anticancer drug candidates that are ROS-dependently trapped in tumor cells [54]. A click chemistry-based 18 F-fluoroglycoconjugation of N-alkylaminoferrocene as a potential anticancer agent was optimized by Toms et al, employing 14 and Cu(OAc) 2, phosphate buffer/THF, and sodium ascorbate for the CuAAC reaction conditions [55]. Noteworthily, the purification of the 18 F-labeled aminoferrocene glycoconjugate was problematic, since the hydrolysis of the boronic acid ester and oxidation of non-carrier-added 26 occurred in the buffered solution.…”

Sweetening Pharmaceutical Radiochemistry by ¹⁸F-Fluoroglycosylation: Recent Progress and Future Prospects

“…Noteworthy, the purification of the 18 F-labeled aminoferrocene glycoconjugate was problematic, since hydrolysis of the boronic acid ester and oxidation of non-carrier-added 26 occurred in buffered solution. However, the RCY (referred to the CuAAC reaction) of carrier-added 26 was 85% under optimized conditions [56]. Further PET studies in PC3 and AR42J tumor-bearing mice demonstrated that carrier-added 26 showed a 2−3-fold higher tumor uptake at 45-60 min p.i.…”

“…Tracers for imaging the content of reactive oxygen species (ROS) in tumors could be valuable for PET imaging of tumors and contribute to our knowledge of the biodistribution of anticancer drug candidates that are ROS-dependently trapped in tumor cells [55]. A click chemistry based 18 F-fluoroglycoconjuation of N-alkylaminoferrocene as a potential anticancer agent was optimized by Toms et al, employing 14 and Cu(OAc)2, phosphate buffer/THF, and sodium ascorbate for the CuAAC reaction conditions [56]. Noteworthy, the purification of the 18 F-labeled aminoferrocene glycoconjugate was problematic, since hydrolysis of the boronic acid ester and oxidation of non-carrier-added 26 occurred in buffered solution.…”

Aminoferrocene‐Based Anticancer Prodrugs Labelled with Cyanine Dyes for in vivo Imaging

“…This compound was prepared by conjugation of 6‐deoxy‐6‐[ 18 F]fluoro‐β‐glucopyranosyl azide [6] via the reaction of copper(I)‐catalyzed azide−alkyne 1,3‐dipolar cycloaddition (CuAAC) [5] . The studies of the biodistribution of conjugate 2 in mice using PET provided first valuable insights into stability and tumor uptake of NAAF prodrugs in vivo [5,7] . However, their important limitation was the relatively short observation time.…”