Tetrazine-Derived Near-Infrared Dye for Targeted Photoacoustic Imaging of Bone.
Rowan SwannSamantha SlikboerAfaf R GenadyLuis Rafael SilvaNancy JanzenAmber FaradayJohn F ValliantSaman SadeghiPublished in: Journal of medicinal chemistry (2023)
A near-infrared photoacoustic probe was used to image bone in vivo through active and bioorthogonal pretargeting strategies that utilized coupling between a tetrazine-derived cyanine dye and a trans -cyclooctene-modified bisphosphonate. In vitro hydroxyapatite binding of the probe via active and pretargeting strategies showed comparable increases in percent binding vs a nontargeted control. Intrafemoral injection of the bisphosphonate-dye conjugate showed retention out to 24 h post-injection, with a 14-fold increase in signal over background, while the nontargeted dye exhibited negligible binding to bone and signal washout by 4 h post-injection. Intravenous injection, using both active and pretargeting strategies, demonstrated bone accumulation as earlier as 4 h post-injection, where the signal was found to be 3.6- and 1.5-fold higher, respectively, than the signal from the nontargeted dye. The described bone-targeted dye enabled in vivo photoacoustic imaging, while the synthetic strategy provides a convenient building block for developing new targeted photoacoustic probes.
Keyphrases
- bone mineral density
- fluorescence imaging
- highly efficient
- bone regeneration
- bone loss
- cancer therapy
- ultrasound guided
- soft tissue
- high resolution
- postmenopausal women
- living cells
- aqueous solution
- deep learning
- quantum dots
- single molecule
- photodynamic therapy
- small molecule
- machine learning
- low dose
- drug delivery
- dna binding