Three-Dimensional Tumor Margin Demarcation Using the Hybrid Tracer Indocyanine Green-^99mTc-Nanocolloid: A Proof-of-Concept Study in Tongue Cancer Patients Scheduled for Sentinel Node Biopsy

Abstract

For radical resection of squamous cell carcinoma of the oral cavity, a tumor-free margin of at least 5 mm is required. Unfortunately, establishing in-depth margins is a surgical conundrum. Knowing that the hybrid sentinel node (SN) tracer indocyanine green (ICG)-99m Tcnanocolloid generates temporary tattoolike markings at the site of administration, we studied the ability to apply this tracer for tumor margin demarcation combined with SN biopsy. Methods: Nineteen patients with clinical T1-T2 oral tongue tumors received the traditional superficial 3 or 4 deposits of ICG-99m Tc-nanocolloid (0.1 mL each), and in 12 patients additional deposits were placed deeply using ultrasound guidance (total of 6; 0.07 mL each). SN mapping was performed using lymphoscintigraphy and SPECT/CT. Before and directly after tumor excision, fluorescence imaging was performed to monitor the tracer deposits in the patient (fluorescent deposits were not used to guide the surgical excision). At pathologic examination, primary tumor samples were studied in detail. Results: The number of tracer depositions did not induce a significant difference in the number of SNs visualized (P 5 0.836). Reproducible and deep tracer deposition proved to be challenging. The fluorescent nature of ICG-99m Tc-nanocolloid supported in vivo and ex vivo identification of the tracer deposits surrounding the tumor. Pathologic examination indicated that in 66.7% (8/12), all fluorescence was observed within the resection margins. Conclusion: This study indicates that tumor margin demarcation combined with SN identification has potential but that some practical challenges need to be overcome if this technique is to mature as a surgical guidance concept. Future studies need to define whether the technology can improve the radical nature of the resections.

99mTc-68Ga-ICG-Labelled Macroaggregates and Nanocolloids of Human Serum Albumin: Synthesis Procedures of a Trimodal Imaging Agent Using Commercial Kits

“…Tagging yield and stability tests confirm its robust and stable bonding with MAA and NC. e amount of free fluorophore, observed by ITLC after labelling, does not condition its in vivo applications, due to its short biological half-life in the human body, as demonstrated by other authors [18]. Several clinical trials have used 99m Tc-ICG-NC without evaluating the ICG percentage bound to NC [19].…”

“…Several examples of a bimodal approach are present in the literature [1,2,[18][19][20], while to our knowledge, this is the first attempt to label HSA particles using a tri-modal method.…”

Sentinel lymph node biopsy in oral cavity cancer using indocyanine green: A systematic review and meta-analysis

“…As shown in the above results, the pooled sensitivity and specificity of free ICG (n=11) were 86.0% (95% CI, 42.0-100.0) and 92% (95% CI, 89.0-95.0) in three studies (Figure 5a) (8,13). Assessment of ICG-99m Tc-nanocolloid (n=45) (11,18,20,21) or the combination of ICG-99m Tc-nanocolloid and blue dye (n=59) (12,19) showed that they had a higher sensitivity (Figure 5b, c). It was also concluded from Figure 4 that ICG combined with methylene blue had higher sensitivity (91%) and specificity (87%) (15).…”

“…In this meta-analysis, we included ICG in combination with blue dye or nuclides in the SLNB of oral cavity cancer and performed sensitivity and specificity analyses accordingly. The results showed that the hybrid ICG-99m Tc-nanocolloid could increase the sensitivity of metastatic LN detection to 87% (95% CI, 60-96), and there were no FN cases in the limited sample size (11,18,20,21). Similarly, ICG in combination with methylene blue exhibited higher sensitivity than ICG alone (15).…”

Multi-Wavelength Fluorescence in Image-Guided Surgery, Clinical Feasibility and Future Perspectives

“…Furthermore, the wavelength dependent tissue penetration of fluorescent dyes may be explored to assess the depth of the target (see Figure 6). [114][115][116] Next to out-of-the-box extensions in radiological tumor marking, 114,117,118 in the future multiwavelength fluorescence imaging is likely to impact other surgical indications such as, but not limited to, bone perfusion, [119][120][121] gastro-intestinal surgery, [122][123][124] bronchoscopy, 125 breast cancer surgery, [126][127][128] head and neck surgery, [129][130][131] ovarian cancer surgery, 132 nerve sparing surgery 110,112,133 and cardiac perfusion and coronary angiography. 134 Besides the use of conventional fluorescence imaging approaches there are a variety of alternative optical imaging methods available that could potentially enhance surgical guidance by supporting multi-signal imaging solutions.…”