Tetrazine-Derived Near-Infrared Dye for Targeted Photoacoustic Imaging of Bone

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.

Automated summary

A near-infrared photoacoustic probe was developed for in vivo bone imaging using active and bioorthogonal pretargeting strategies. The probe showed comparable binding to hydroxyapatite in vitro compared to a nontargeted control. In vivo studies demonstrated retention and increased signal in bone when the probe was injected intrafemorally and intravenously using active and pretargeting strategies, respectively. The bone-targeted dye enables photoacoustic imaging, and the synthetic strategy provides a convenient platform for developing new targeted photoacoustic probes.