Abstract
1604
Objectives: Copper is a transition metal element that plays an important role in many physiological activities, and its dyshomeostasis is related to cancer as well as neurodegenerative diseases. Copper-targeted probes with single imaging modality have been extensively reported. Herein, we describe a multimodality fluorescence/19F MR/PET imaging agent by incorporating a fluorine atom into an aggregation-induced emission (AIE) luminogen targeting Cu2+.
Methods: The probe FN was synthesized conveniently from commercially available fluoro compound. The interaction, binding constant and selectivity studies between the probe and Cu2+ were evaluated by fluorimetric titration. The 19F relaxation times with and without Cu2+ were also measured. The probe was used in fluorescence imaging and 19F phantom imaging. Additionally, the corresponding 18F-isotopologues, [18F]FN, was synthesized via spirocyclic iodonium ylide (SCIDY) strategy. [18F]FN was then used as a radioactive tracer in the PET imaging of a healthy macaque.
Results: FN showed a typical AIE characteristics, and it could specifically bind with Cu2+ to form FN-Cu2+ complex, with the binding constant (KB) as 6.140 × 105 M-1. The detection limit of FN towards Cu2+ was determined as 160 nM. The fluorescence emission of FN could be quenched to 0.5% as a result of an excess of Cu2+, and then recovered after the consecutive addition of S2-.Confocal imaging demonstrated the application in the detection of Cu2+ and H2S in living cells. Onthe other hand, the presence of Cu2+ could significantly accelerate the relaxations and shorten the relaxation times (T1= 1207 ms, T2 = 699 ms for FN; T1= 34 ms, T2 = 13.9 ms for FN-Cu2+). Phantom image also indicated its possibility of being a 19F MR contrast agent. The radiosynthesis of [18F]FN was realized using a commercial GE TRACERlab FX2 N radiosynthesis module, leading to 10 ± 3% non-decay corrected radiochemical yields (n.d.c. RCYs) within 110 min with >99% radiochemical and chemical purity and specific activity of 29.6 GBq/μmol (0.8 Ci/μmol). [18F]FN was used to the whole-body dynamic PET imaging of a healthy macaque for biodistribution study.
Conclusions: We have developed a small-molecular probe FN that is capable of fluorescence/19F MR/PET imaging. Confocal imaging revealed the application in the detection of Cu2+ and H2S in living cells. Phantom image also indicated its possibility of being a 19F MR contrast agent. Furthermore, we have finished the radiosynthesis of [18F]-FN, which was able to use as a tracer in PET imaging.