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Metastatic status of sentinel lymph nodes in breast cancer determined with photoacoustic microscopy via dual-targeting nanoparticles.

ABSTRACT: Detection of sentinel lymph nodes (SLNs) is critical to guide the treatment of breast cancer. However, distinguishing metastatic SLNs from normal and inflamed lymph nodes (LNs) during surgical resection remains a challenge. Here, we report a CD44 and scavenger receptor class B1 dual-targeting hyaluronic acid nanoparticle (5K-HA-HPPS) loaded with the near-infra-red fluorescent dye DiR-BOA for SLN imaging in breast cancer. The small sized (~40 nm) self-assembled 5K-HA-HPPSs accumulated rapidly in the SLNs after intradermal injection. Compared with normal popliteal LNs (N-LN), there were ~3.2-fold and ~2.4-fold increases in fluorescence intensity in tumour metastatic SLNs (T-MLN) and inflamed LNs (Inf-LN), respectively, 6 h after nanoparticle inoculation. More importantly, photoacoustic microscopy (PAM) of 5K-HA-HPPS showed a significantly distinct distribution in T-MLN compared with N-LN and Inf-LN. Signals were mainly distributed at the centre of T-MLN but at the periphery of N-LN and Inf-LN. The ratio of PA intensity (R) at the centre of the LNs compared with that at the periphery was 5.93 ± 0.75 for T-MLNs of the 5K-HA-HPPS group, which was much higher than that for the Inf-LNs (R = 0.2 ± 0.07) and N-LNs (R = 0.45 ± 0.09). These results suggest that 5K-HA-HPPS injection combined with PAM provides a powerful tool for distinguishing metastatic SLNs from pLNs and inflamed LNs, thus guiding the removal of SLNs during breast cancer surgery.

SUBMITTER: Dai Y

PROVIDER: S-EPMC7494891 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundIn the post-Z0011 era, sentinel lymph node (SLN) status and metastatic burden determine whether axillary management entails conservative sentinel lymph node biopsy (SLNB) or radical axillary lymph node dissection (ALND) in breast cancer patients. However, SLN status and metastatic burden cannot be evaluated preoperatively in clinical practice. This study explored the predictive value of contrast-enhanced ultrasound (CEUS) patterns of SLN to assess the nodal status and metastatic burden in early breast cancer patients.MethodsA retrospective study was conducted on 88 consecutive patients who were diagnosed with clinical T1-2N0 breast cancer between December 2020 and November 2021 at the Lanzhou University Second Hospital and scheduled for SLNB. Preoperative CEUS was performed to confirm the location and enhancement pattern of the SLN, and the conventional ultrasonic characteristics of the primary breast lesions and SLN were recorded. Intraoperative localized SLN and postoperative pathological results were used as the gold standard for comparison with preoperative ultrasound findings.ResultsCEUS successfully identified at least 1 SLN in 88 patients, with a total of 118 SLNs identified in the entire cohort. Univariate analysis showed that lesion size, blood flow grade, SLN longitudinal diameter, cortical thickness, and enhancement pattern were significant predictive features of SLN metastasis. Further multiple regression analysis indicated that the enhancement pattern of the SLN was an independent risk factor for SLN metastasis, with a sensitivity and a specificity of 84.2% (32/38) and 80.0% (40/50), respectively. Meanwhile, the SLN enhancement pattern could predict the lymph node metastasis burden (P<0.001). In patients presenting with a type I (homogeneous enhancement) or type II (heterogeneous enhancement) SLN, 91.5% (65/71) had ≤2 positive SLNs, whereas in patients with a type III (no enhancement) SLN, 70.6% (12/17) had >2 metastatic nodes.ConclusionsThe contrast-enhanced pattern of the SLN is an independent risk factor for SLN status. Patients presenting with a type I or type II SLN enhanced pattern are unlikely to have high-burden metastases detected at their final surgical treatment and omission of ALND may be appropriate.

Project description:PurposeTo noninvasively map sentinel lymph nodes (SLNs) and lymphatic vessels in rats in vivo by using dual-modality nonionizing imaging-volumetric spectroscopic photoacoustic imaging, which measures optical absorption, and planar fluorescence imaging, which measures fluorescent emission-of indocyanine green (ICG).Materials and methodsInstitutional animal care and use committee approval was obtained. Healthy Sprague-Dawley rats weighing 250-420 g (age range, 60-120 days) were imaged by using volumetric photoacoustic imaging (n = 5) and planar fluorescence imaging (n = 3) before and after injection of 1 mmol/L ICG. Student paired t tests based on a logarithmic scale were performed to evaluate the change in photoacoustic signal enhancement of SLNs and lymphatic vessels before and after ICG injection. The spatial resolutions of both imaging systems were compared at various imaging depths (2-8 mm) by layering additional biologic tissues on top of the rats in vivo. Spectroscopic photoacoustic imaging was applied to identify ICG-dyed SLNs.ResultsIn all five rats examined with photoacoustic imaging, SLNs were clearly visible, with a mean signal enhancement of 5.9 arbitrary units (AU) + or - 1.8 (standard error of the mean) (P < .002) at 0.2 hour after injection, while lymphatic vessels were seen in four of the five rats, with a signal enhancement of 4.3 AU + or - 0.6 (P = .001). In all three rats examined with fluorescence imaging, SLNs and lymphatic vessels were seen. The average full width at half maximum (FWHM) of the SLNs in the photoacoustic images at three imaging depths (2, 6, and 8 mm) was 2.0 mm + or - 0.2 (standard deviation), comparable to the size of a dissected lymph node as measured with a caliper. However, the FWHM of the SLNs in fluorescence images widened from 8 to 22 mm as the imaging depth increased, owing to strong light scattering. SLNs were identified spectroscopically in photoacoustic images.ConclusionThese two modalities, when used together with ICG, have the potential to help map SLNs in axillary staging and to help evaluate tumor metastasis in patients with breast cancer.

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Metastatic status of sentinel lymph nodes in breast cancer determined with photoacoustic microscopy via dual-targeting nanoparticles.

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