Performance of Molecular Lymphosonography for Detection and Quantification of Metastatic Involvement in Sentinel Lymph Nodes

Abstract

Objectives To assess the performance of molecular lymphosonography with dual‐targeted microbubbles in detecting and quantifying the metastatic involvement in sentinel lymph nodes (SLNs) using a swine melanoma model. Methods Targeted microbubbles were labeled with P‐selectin and αVβ3‐integrin antibodies. Control microbubbles were labeled with immunoglobulin G antibodies. First lymphosonography with Sonazoid (GE Healthcare, Oslo, Norway) was used to identify SLNs. Then dual‐targeted and control microbubbles were injected intravenously to detect and quantify metastatic disease in the SLNs. Distant non‐SLNs were imaged as benign controls. All evaluated lymph nodes (LNs) were surgically removed, and metastatic involvement was characterized by a histopathologic analysis. Two radiologists blinded to histopathologic results assessed the baseline B‐mode images of LNs, and the results were compared to the histologic reference standard. The mean intensities of targeted and control microbubbles within the examined LNs were measured and compared to the LN histologic results. Results Thirty‐five SLNs and 34 non‐SLNs from 13 Sinclair swine were included in this study. Twenty‐one SLNs (62%) were malignant, whereas 100% of non‐SLNs were benign. The sensitivity of B‐mode imaging for metastatic LN diagnosis for both readers was relatively high (90% and 71%), but the specificity was very poor (50% and 58%). The sensitivity and specificity of molecular lymphosonography for metastatic LN detection were 91% and 67%, respectively. The mean intensities from dual‐targeted microbubbles correlated well with the degree of metastatic LN involvement (r = 0.6; P < 0.001). Conclusions Molecular lymphosonography can increase the specificity of metastatic LN detection and provide a measure to quantify the degree of metastatic involvement.

Microbubble-Assisted Ultrasound for Imaging and Therapy of Melanoma Skin Cancer: A Systematic Review

“…Secondary LNs detected using CEUS were nearly five times more likely to contain melanoma metastases than those removed using radical LN dissection. Recently, Nam et al, investigated the performance of molecular US imaging with dual-targeted MBs to detect melanoma metastases in SLNs in a swine melanoma model (Nam, et al 2018, Nam, et al 2019).…”

Molecular Sonography: Current and Future Applications

“…This is only available from a few manufacturers on an investigational basis. We reported our early experience developing a labeled microbubble [7].…”

“…Labeled microbubbles have also been used in detecting prostate cancer and sentinel lymph nodes [7,8]. Molecular lymphosonography was used to detect metastatic involvement in a swine melanoma model.…”

Sentinel lymph node mapping in endometrial cancer after 2020 ESGO-ESTRO-ESP consensus update: what will happen in the next few years?

“…Generally, routine preoperative ultrasound assessment of regional lymph nodes in cancer patients does not provide reliable nodal staging, because SLN tumor volume is too small to be reliably detected [32]. More reliable results are obtained by use of real-time tissue elastography [33] or contrast-enhanced ultrasound imaging [34]. Nam et al proved in swine melanoma model that such molecular lymphosonography with the use of targeted microbubbles labelled with P-selectin and α V β 3 -integrin antibodies can increase the specificity of metastatic SLN detection and provide a measure to quantify the extent of metastatic involvement [34].…”

“…More reliable results are obtained by use of real-time tissue elastography [33] or contrast-enhanced ultrasound imaging [34]. Nam et al proved in swine melanoma model that such molecular lymphosonography with the use of targeted microbubbles labelled with P-selectin and α V β 3 -integrin antibodies can increase the specificity of metastatic SLN detection and provide a measure to quantify the extent of metastatic involvement [34]. There is no data in the literature regarding application of this method in gynaecological malignancies except for vulvar cancer, which metastasizes to relatively easy accessible superficially located inguinal and femoral lymph nodes.…”