No abstract

A small library of [2 + 1] 99mTc(i) complexes based on phenyl-imidazole-fused phenanthroline (PIP) ligands were synthesized and evaluated as multimodal molecular imaging probes.

Tailoring carbon nanotube surface chemistry is essential for biomedical applications. Bisphosphonate–carbon nanotube conjugates were prepared to target regions of active bone metabolism. The conjugates were synthesized using covalent functionalization (G1) or latently reactive polymer–nanotube complexes (G2), and it was found that the noncovalent G2 method afforded higher quality colloidal dispersions. The in vitro cytotoxicity tests against C2C12 cells were carried out and the results revealed low cytotoxicity and good biocompatibility profile for both bisphosphonate–carbon nanotube conjugates. The conjugates were radiolabeled with 99mTc in high radiochemical yield (80–92%). In vitro binding studies to hydroxyapatite showed binding of 77 and 36% for G1 and G2, respectively, after 1 h incubation at room temperature. A biodistribution study of G1 and G2 in vivo in a Balb/c mouse model demonstrated rapid blood clearance after 1 h and superior bone localization of G2 conjugates as compared to G1 conjugates. Photoacoustic imaging of nanotube conjugates confirmed superior in vivo bone localization of G2 as compared to G1. Together, biodistribution studies of radiolabeled complexes and photoacoustic imaging demonstrated that latently reactive polymer–nanotube complexes are a promising platform to modulate carbon nanotube surface chemistry for targeted diagnostic and drug delivery.

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.

No abstract