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.