Contrast‐Enhanced Ultrasound With Perflubutane for Sentinel Lymph Node Mapping in Cutaneous Melanoma: A Pilot Study

Abstract

Objective To study the feasibility of contrast‐enhanced ultrasound (CEUS) for identification of SLN associated with cutaneous melanoma. Study Design Single arm pilot study in a swine animal model. Methods One milliliter of perflubutane (Sonazoid, GE Healthcare, Milwaukee, WI) was injected into the peritumoral dermis in five swine with cutaneous melanoma. Ultrasonography was used to follow enhancing lymphatic channels to lymph nodes (LN). Intradermal injection of vital blue (VB) dye was used as a positive control. LN identified by either method were excised and examined histologically. Results There were five primary cutaneous melanomas with mean area of 4.36 ± 4.75 cm2 and Breslow depth of 3.6 ± 1.5 mm. Six possible sentinel lymph node (SLN)s were identified with CEUS, and nine were identified with VB. SLN averaged 12.44 ± 6.15 cm from the primary tumor. Four of six (67%) SLNs identified by CEUS and four of nine (44%) candidate SLNs identified by VB contained histologically confirmed metastatic melanoma. All six CEUS‐identified SLNs were also identified with VB. Two LNs not containing melanoma were identified by CEUS; three were identified with VB. In all SLN with metastases, metastatic cells were scattered throughout the LN and not clustered in a discrete mass. Conclusion CEUS with perflubutane feasibly identifies SLN associated with cutaneous melanoma and may be a useful adjunct technology in facilitating precise SLN dissection. Our work supports a clinical trial investigating the use of CEUS for this application. Level of Evidence NA Laryngoscope, 129:1117–1122, 2019

Therapeutic oxygen delivery by perfluorocarbon-based colloids

“…This technique offers a non-invasive liquid biopsy approach for metastatic cancer staging and treatment. PFC-labeled MBs can thus help biopsy sentinel lymph nodes in breast cancer, potentially replacing axillary surgery [478,479], and has entered routine practice in certain medical centers [480]. Targeted USpheres MBs were used for in vivo characterization of programmed death ligand-1 (PD-L1)-expressing cells in a mouse model [481].…”

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

“…Nevertheless, the efficiency of CEUS for SLN characterization (benign versus malignant) is limited. Recently, Bertelsen et al, confirmed these results and suggested that CEUS may be useful for accurate SLN dissection (Figure 4) (Bertelsen, et al 2019). Moreover, Liu et al, reported that secondary LNs can also be detected with CEUS after direct injection of MBs into contrast-enhanced SLNs .…”

“…However, Bertelsen et al, identified three main limitations of this method (Bertelsen, et al 2019): 1) the radiotracer detects secondary LNs, resulting in their dissections, thereby increasing operative time and morbidity; 2) if the primary lesion is located near the draining nodal basins in areas with a dense lymphatic supply, the use of a hand-held gamma probe is more challenging; and 3) lymphoscintigraphy does not offer depth information for anatomic SLN localization. To overcome this issue, the surgeon removes LNs and assesses them ex-vivo using a gamma probe.…”

Contrast-enhanced ultrasound: a new tool for imaging the superficial lymphatic vessels of the upper limb

“…Perflubutane is a relatively new, second generation US contrast agent with some additional characteristics over the more commonly used sulfur hexafluoride (Sonovue®, Bracco, Milan, Italy) such as its affinity for reticuloendothelial cells [ 23 , 24 ]. Like sulfur hexafluoride, it is well tolerated and has no major contraindications or severe known adverse effects when administered by intravenous or subdermal injections [ 25 , 26 ].…”