Evaluation of optical imaging agents in a fluorescence-guided surgical model of head and neck cancer

• Published in: Surgical oncology Vol. 27; no. 2; pp. 225 - 230
• Main Authors: Prince, Andrew C., Moore, Lindsay S., Tipirneni, Kiranya E., Ramesh, Tushar, Limdi, Mihir A., Bevans, Stephanie L., Walsh, Erika M., Greene, Benjamin, Rosenthal, Eben L., Warram, Jason M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.06.2018; Elsevier Limited
• Subjects: Animals; Cancer; Carcinoma, Squamous Cell - diagnostic imaging; Carcinoma, Squamous Cell - secondary; Carcinoma, Squamous Cell - surgery; Contrast agents; Female; Fluorescence; Fluorescence imaging; Fluorescent Dyes; Fluorescent indicators; Head; Head & neck cancer; Head and neck cancer; Head and Neck Neoplasms - diagnostic imaging; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - surgery; Humans; I.R. radiation; Intravenous administration; Localization; Lung diseases; Lymphatic system; Medical imaging; Metastases; Metastasis; Mice; Mice, Nude; Models, Anatomic; Optical guided surgery; Optical Imaging - methods; Probes; Receptors; Squamous cell carcinoma; Surgeons; Surgery; Surgery, Computer-Assisted - methods; Surgical oncology; Tumor Cells, Cultured; Tumors; Xenografts; Xenotransplantation; MFI; FLI; Fluorescence imaging; FGS; TTR; TBR; NIR; HNSCC; Head and neck cancer; Surgical oncology; Optical guided surgery; BLI
• ISSN: 0960-7404; 1879-3320
• DOI: 10.1016/j.suronc.2018.04.004

Tumor proliferation often occurs from pathologic receptor upregulation. These receptors provide unique targets for near-infrared (NIR) probes that have fluorescence-guided surgery (FGS) applications. We demonstrate the use of three smart-targeted probes in a model of head and neck squamous cell carcinoma. A dose escalation study was performed using IntegriSense750, ProSense750EX, and ProSense750FAST in mice (n = 5) bearing luciferase-positive SCC-1 flank xenograft tumors. Whole body fluorescence imaging was performed serially after intravenous injection using commercially available open-field (LUNA, Novadaq, Canada) and closed-field NIR systems (Pearl, LI-COR, Lincoln, NE). An ex vivo, whole-body biodistribution was conducted. Lastly, FGS was performed with IntegriSense750 to demonstrate orthotopic and metastatic disease localization. Disease fluorescence delineation was assessed by tumor-to-background fluorescence ratios (TBR). Peak TBR values were 3.3 for 1 nmol ProSense750EX, 5.5 for 6 nmol ProSense750FAST, and 10.8 for 4 nmol IntegriSense750 at 5.5, 3, and 4 d post administration, respectively. Agent utility is unique: ProSense750FAST provides sufficient contrast quickly (TBR: 1.5, 3 h) while IntegriSense750 produces strong (TBR: 10.8) contrast with extended administration-to-resection time (96 h). IntegriSense750 correctly identified all diseased nodes in situ during exploratory surgeries. Ex vivo, whole-body biodistribution was assessed by tumor-to-tissue fluorescence ratios (TTR). Agents provided sufficient fluorescence contrast to discriminate disease from background, TTR>1. IntegriSense750 was most robust in neural tissue (TTR: 64) while ProSense750EX was superior localizing disease against lung tissue (TBR: 13). All three agents appear effective for FGS.