Synthesis and characterization of [18F]BF2-2,4-pentanedione derivatives

Objectives 18F-labeled BODIPY has been successfully synthesized for hybrid PET/optical imaging. Curcumin, a major component of curry spice, has diverse biological activity with weak fluorescence. Recently, red-shifted BF2-curcumin derivatives have been developed for near-infrared imaging of β-amyloid plaques. In this study, we carried out 18F-labeling of BF2-2,4-pentanedione derivatives, and applied this technology to synthesis of a [18F]BF2-curcumin derivative ([18F]1) and evaluated its in vivo characteristics.

Methods Non-radioactive BF2-2,4-pentanedione derivatives were synthesized from 2,4-pentanedione derivatives and BF3∙etherate. 18F-labeling was conducted on these derivatives by a one-pot 19F/18F exchange reaction via activated triflate intermediate. BF2-curcumin derivative (1) was synthesized, and its photophysical properties, including excitation and emission spectra were measured using a fluorometer. [18F]1 was synthesized as described for synthesis of BF2-3,5-pentanedione derivative. Partition coefficient of [18F]1 was measured using a 1:1 mixture of water and 1-octanol to predict its lipophilicity. Tissue distribution study was performed using ICR mice injected with [18F]1. At the indicated time points, mice were sacrificed, and tissues of interest were extracted, weighed, and counted.

Results Of BF2-2,4-pentanedione derivatives, one derivative was labeled with 18F. Based on BF2-3,5-pentanedione derivative and curcumin backbone, non-radioactive ligand 1 was synthesized in high yield. It displayed an excitation maximum peak (λex) at 520 nm and an emission maximum peak (λem) at 690 nm, which is suitable for in vivo optical imaging. [18F]1 was readily synthesized in 5 min from 19F/18F exchange reaction. Decay-corrected radiochemical yield of [18F]1 was 25-35%, and its specific activity was higher (38 GBq/μmol) than those of 18F-labeled BODIPY compounds. Partition coefficient measurement of [18F]1 gave log Po/w value of 2.8, suggesting its appropriate lipophilicity for brain permeability. Tissue distribution of [18F]1 showed high radioactivity accumulation in the kidney (5.49% ID/g) at 2 min after injection and decreased over time. The brain uptake of [18F]1 was 3.49% ID/g 2 min after injection with fast wash-out at 30 min (0.08% ID/g). However, there was high femur uptake at 30 min after injection, indicating in vivo metabolic defluorination.

Conclusions This is the first study of 19F/18F exchange reaction on BF2-curcumin derivative. Further studies are warranted to design metabolically stable [18F]BF2-curcumin derivatives.