Use Of Ultrasmall Core-Shell Fluorescent Silica Nanoparticles For Image-Guided Sentinel Lymph Node Biopsy In Head And Neck Melanoma A Nonrandomized Clinical Trial

Importance Sentinel lymph node (SLN) mapping agents approved for current surgical practice lack sufficient brightness and target specificity for high-contrast, sensitive nodal visualization. Objective To evaluate whether an ultrasmall, molecularly targeted core-shell silica nanoparticle (Cornell prime dots) can safely and reliably identify optically avid SLNs in head and neck melanoma during fluorescence-guided biopsy. Design, Setting, and Participants This nonrandomized clinical trial enrolled patients aged 18 years or older with histologically confirmed melanoma in whom SLN mapping was indicated. Exclusion criteria included known pregnancy, breast-feeding, or medical illness unrelated to the tumor. The trial was conducted between February 2015 and March 2018 at Memorial Sloan Kettering Cancer Center, with postoperative follow-up of 2 years. Data analysis was conducted from February 2015 to March 2018. Interventions Patients received standard-of-care technetium Tc 99m sulfur colloid followed by a microdose administration of integrin-targeting, dye-encapsulated nanoparticles, surface modified with polyethylene glycol chains and cyclic arginine-glycine-aspartic acid-tyrosine peptides (cRGDY-PEG-Cy5.5-nanoparticles) intradermally. Main Outcomes and Measures The primary end points were safety, procedural feasibility, lowest particle dose and volume for maximizing nodal fluorescence signal, and proportion of nodes identified by technetium Tc 99m sulfur colloid that were optically visualized by cRGDY-PEG-Cy5.5-nanoparticles. Secondary end points included proportion of patients in whom the surgical approach or extent of dissection was altered because of nodal visualization. Results Of 24 consecutive patients enrolled (median [interquartile range] age, 64 [51-71] years), 18 (75%) were men. In 24 surgical procedures, 40 SLNs were excised. Preoperative localization of SLNs with technetium Tc 99m sulfur colloid was followed by particle dose-escalation studies, yielding optimized doses and volumes of 2 nmol and 0.4 mL, respectively, and maximum SLN signal-to-background ratios of 40. No adverse events were observed. The concordance rate of evaluable SLNs by technetium Tc 99m sulfur colloid and cRGDY-PEG-Cy5.5-nanoparticles was 90% (95% CI, 74%-98%), 5 of which were metastatic. Ultrabright nanoparticle fluorescence enabled high-sensitivity SLN visualization (including difficult-to-access anatomic sites), deep tissue imaging, and, in some instances, detection through intact skin, thereby facilitating intraoperative identification without extensive dissection of adjacent normal tissue or nerves. Conclusions and Relevance This study found that nanoparticle-based fluorescence-guided SLN biopsy in head and neck melanoma was feasible and safe. This technology holds promise for improving lymphatic mapping and SLN biopsy procedures, while potentially mitigating procedural risks. This study serves as a first step toward developing new multimodal approaches for perioperative care.Question Can the favorable properties of an ultrasmall fluorescent core-shell silica nanoparticle aid real-time image-guided detection, localization, and surgical management of sentinel lymph nodes (SLNs) in patients with head and neck melanoma? Findings In this nonrandomized clinical trial of 24 patients, real-time, particle-based fluorescence imaging of SLNs was feasible and safe at the microdosing level and enabled deep-tissue nodal detection. There was high concordance in identifying nodes between preoperative lymphoscintigraphy and particle-based fluorescence-guided biopsy. Meaning The findings of this study suggest that ultrabright, optical contrast-conferring particles for SLN identification hold promise for overcoming current probe limitations and improving surgical outcomes.This nonrandomized clinical trial evaluates whether an ultrasmall, molecularly targeted core-shell silica nanoparticle can safely and reliably identify optically avid SLNs in head and neck melanoma during fluorescence-guided biopsy.