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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., Trial Registration: ClinicalTrials.gov Identifier: NCT02106598.

Oral cancer is one of the most common cancers globally. Survival rates for patients are directly correlated with stage of diagnosis; despite this knowledge, 60% of individuals are presenting with late-stage disease. Currently, the initial evaluation of a questionable lesion is performed by a conventional visual examination with white light. If a lesion is deemed suspicious, a biopsy is taken for diagnosis. However, not all lesions present suspicious under visual white light examination, and there is limited specificity in differentiating between benign and malignant transformations. Several vital dyes, light-based detection systems, and cytology evaluation methods have been formulated to aid in the visualization process, but their lack of specific biomarkers resulted in high false-positive rates and thus limits their reliability as screening and guidance tools. In this review, we will analyze the current methodologies and demonstrate the need for specific intraoral imaging agents to aid in screening and diagnosis to identify patients earlier. Several novel molecular imaging agents will be presented as, by result of their molecular targeting, they aim to have high specificity for tumor pathways and can support in identifying dysplastic/cancerous lesions and guiding visualization of biopsy sites. Imaging agents that are easy to use, inexpensive, noninvasive, and specific can be utilized to increase the number of patients who are screened and monitored in a variety of different environments, with the ultimate goal of increasing early detection.