Abstract
157
Objectives We have previously reported Maillard reaction of 18F-FDG with biological amines resulting in formation of 18F-fluorodeoxyglycosylamines (18F-FDGly) as pseudo-Amadori products. To increase in vivo stability, we report the reductive amination of FDGly to provide reduced FDGly (rFDGly). rFDGly has the potential of linking 18F-FDG (hydrophilic) to lipophilic molecules containing amine group and may be useful as PET imaging agents in vivo.
Methods Respective amines, 6-OH-BTA-0 (PIB precursor, BTA) and N,N-dimethyl-4,4’-azodianiline (TAZA) were mixed with FDG under anhydrous conditions (MeOH, molecular sieves, NaCNBH3, and acetic acid). After products were isolated, rFDGly derivatives were evaluated by displacement studies on brain slices. Respective rFDGly (rFDGBTA and rFDGTAZA) were compared with 11C-TAZA and 11C-PIB. Radiolabeled products were investigated by radiosynthesis using 18F-FDG (1-5 mCi). Radiolabeled 18F-FDGBTA was evaluated for binding to postmortem human brain Aβ-amyloid sites.
Results Stable products of rFDGBTA and rFDGTAZA were isolated in 94% and 36% yield respectively. The formation of pseudo-Amadori product occurs in aqueous and nonaqueous conditions to form FDGly/18F-FDGly derivatives. The coupling of amines with FDG is improved by reductive amination because the reversibility of the Schiff base reaction is removed upon reduction. In vitro binding of 18F-FDGBTA (51% radiosynthesis yield) to human Aβ-amyloid plaque regions were observed lower when measured with 11C-PIB and 11C-TAZA in human brain slices. In vivo stability of 18F-FDGBTA, 18F-rFDGBTA and 18F-rFDGTAZ needs to be determined.
Conclusions Optimization of the semi-anhydrous reductive amination conditions for the radiosynthesis of 18F-rFDGBTA and 18F- rFDGTAZ are currently underway and may help formulate conditions for 18F-ClickFDG reaction. Although these amine derivatives are stable in vitro and exhibit biological properties, stability in vivo is being investigated.