The lymphatic system plays a crucial role in the spread of solid tumors and is often the first site of metastasis, as cancer cells typically invade nearby lymph nodes (LN) before potentially spreading to other LNs through the lymphatic system and distant organs through the bloodstream

In oral squamous cell carcinoma (OSCC) surgery, inadequate tumor margins are reported in up to 85% of cases, adversely affecting outcomes. In this prospective, single-center study (n = 31; NCT04191460), we evaluated the safety and imaging feasibility of cRGD-ZW800-1, a near-infrared fluorescent integrin-targeted tracer. The secondary objective was to determine whether intraoperative fluorescence imaging could identify inadequate resection margins and inform surgical decision-making. Patients received 0.01, 0.025, or 0.05 mg/kg cRGD-ZW800-1, and tracer uptake was quantified using in vivo multi-diameter single-fiber reflectance and single-fiber fluorescence spectroscopy to optimize dosing and timing. All doses were well tolerated, achieving tumor-to-background ratios exceeding 4.5, with optimal performance at 0.025 mg/kg. Fluorescence imaging detected all 23 inadequate margins, including nine undetected by conventional assessment (sensitivity 100% versus 70%), altered surgical plans in five cases, and avoided adjuvant radiotherapy in three cases. These findings demonstrate that cRGD-ZW800-1 is safe, tumor-specific, and facilitates intraoperative margin assessment in OSCC.

Background: Fracture non-union cause chronic pain, dysfunction, and high healthcare costs. Treatment consists of revitalizing the nonhealed fracture site through debridement, bone resection, grafting, or stabilization if indicated. Adequate bone perfusion is essential for healing, but current intraoperative assessments are subjective. This study explores the feasibility of using quantitative near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG) to assess bone perfusion in non-union surgery. This technique allows real-time visualization of tissue perfusion through tracing intravascular injected ICG. Methods: This prospective, multicenter feasibility study was conducted in 2 Dutch academic hospitals. Intraoperative ICG NIRF imaging was performed in non-union patients after debridement and before osteosynthesis. Time-intensity curves were derived from intraoperative data, and 3 time-related perfusion parameters were extracted to quantify the perfusion in various osseous structures. Demographic data included patient's age, sex, race, and body mass index. Results: ICG NIRF measurement was successfully performed in 20 patients (median age 50.5 years, 65% female, and 90% White) at 7 fracture locations. Three distinct perfusion patterns were observed. (1) rapid ingress and egress, (2) rapid ingress with a plateau phase, and (3) prolonged ingress with no egress within the measurement. The median Tmax was 214 s (inter-quartile range [IQR]): 69-246 s. The normalized maximum ingress slope was 4.4%/s (IQR: 2.4-6.5), and the median Egress-60 was 84.7% (IQR: 77.4-94.8). Conclusion: ICG NIRF imaging is a feasible and reproducible method for intraoperative bone perfusion assessment in fracture non-union, potentially offering an objective measure of bone vitality. Perfusion parameters and time-intensity curves were successfully quantified across various bone structures, revealing patterns similar to those linked with clinical outcomes in other studies. Future research should evaluate how these perfusion patterns relate to bone healing. Level of Evidence: Level II . See Instructions for Authors for a complete description of levels of evidence.

Background/Objectives: Intraoperative fluorescence imaging (FI) with tumor-targeted tracers offers a promising approach to improve surgical precision in cancer surgery. cRGD-ZW800-1, an integrin-targeted fluorescent tracer, has previously demonstrated safety, tumor specificity, and utility in detecting inadequate margins in oral cancer. During this study, we observed variability in background fluorescence between different subsites of the oral cavity. Therefore, this study aimed to systematically evaluate intraoperative in vivo and ex vivo mucosal contrast ratios across various oral cavity subsites using FI with cRGD-ZW800-1. Methods: Thirty-one patients with oral squamous cell carcinoma underwent intraoperative FI following intravenous injection of cRGD-ZW800-1 at least 18 h preoperatively. In vivo imaging was performed using the Quest Spectrum platform. In addition, ex vivo FI of the resected specimen was performed using the Pearl Trilogy Small Animal Imaging System. As these ex vivo images were obtained under uniform and controlled acquisition conditions, they allow for direct comparison with the intraoperative fluorescence signals. Fluorescence intensities and tumor-to-background ratios (TBRs) were assessed per oral subsite using manually drawn regions of interest (ROIs) on the tumor and adjacent healthy mucosa using Quest’s Spectrum Software, version 4.8.2, (in vivo images) and the Pearl’s integrated software ImageStudio version 6.2 (ex vivo images). A TBR ≥ 1.5 was considered sufficient. Results: Under uniform imaging settings, all samples exhibited adequate contrast (TBR ≥ 2.3), allowing clear tumor visualization and precise evaluation of mucosal margins on final histopathology. Notably, intraoperative in vivo contrast in the posterior located maxillary alveolar process was comparatively lower, which was attributable to suboptimal imaging conditions and subsite-specific background fluorescence. Conclusions: Our findings indicate that, although contrast varies across different oral subsites, all specimens exhibited sufficient ex vivo mucosal contrast to allow reliable tumor delineation. As in vivo imaging may be affected by subsite-specific background fluorescence and inherent limitations of intraoperative imaging geometry, fluorescence signals should be interpreted in conjunction with standard visual and tactile assessment. Due to anatomical constraints, different oral subsites may appear within the same field of view, which can influence perceived signal intensity. Therefore, intraoperative ex vivo fluorescence evaluation is recommended for signal interpretation.