The
traditional method of labeling the nonpalpable breast cancer
is placing a guidewire or metal marker guided by ultrasound or stereographic
mammogram prior to surgery. However, the wire localization has a risk
of displacement and could be an obstacle in the surgical course. To
avoid these issues, we tried to combine the near-infrared (NIR) fluorescence
dye dioctadecyltetramethyl indotricarbocyanine iodide (DiR) and microbubbles
(MBs) to realize the dual-modality imaging for breast cancer microfoci
intraoperative identification and guidance as a more efficient workflow.
First, 24 mice were divided into three groups, injected with DiR nanoparticles
(NPs), DiR MBs, and DiR MBs + ultrasound (US), and then, in vivo and
ex vivo NIR fluorescence imaging was conducted. The distinction of
fluorescence imaging intensity at the tumor site among the three groups
was statistically significant (P < 0.001). Group
3 (DiR MBs + US) exhibited the highest fluorescence imaging intensity;
the distinctions between group 3 and group 1 (DiR NPs) and group 3
and group 2 (DiR MBs) were both statistically significant (P = 0.001, P = 0.003), while the distinction
between group 1 and group 2 was not statistically significant (P = 1.0). The results above validated the advantage of fluorescence
imaging by using ultrasound-targeted MB destruction. Second, two kinds
of subcutaneous breast cancer mice models [4T1-luc(n = 5)/MCF-7(n = 3)] received tumor resection, and
NIR fluorescence and bioluminescence images were obtained to detect
tumor residuals. We found that the small residual tumor tissues, metastatic
lymph nodes, and even the surrounding infiltrated tissue all can be
indicated by the fluorescence imaging and verified with bioluminescence
and histological examination. In addition, the residual tumor cells
appeared as tumor recurrence 22 days post operation and was confirmed
with contrast-enhanced ultrasound (CEUS) in vivo. Thereby, ultrasound-targeted
DiR MB destruction and then conversion into DiR NPs was feasible for
intraoperative identification and guidance of nonpalpable breast cancer
foci.