abstract
- 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.