Andrew C Prince1, Lindsay S Moore2, Kiranya E Tipirneni3, Tushar Ramesh1, Mihir A Limdi4, Stephanie L Bevans1, Erika M Walsh2, Benjamin Greene2, Eben L Rosenthal5, Jason M Warram6. 1. University of Alabama School of Medicine, Birmingham, AL, USA. 2. Department of Otolaryngology, University of Alabama at Birmingham, Birmingham, AL, USA. 3. Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA. 4. Rice University, Houston, TX, USA. 5. Department of Otolaryngology, Stanford University, Stanford, CA, USA. 6. Department of Otolaryngology, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: mojack@uab.edu.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: All three agents appear effective for FGS.
BACKGROUND: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. METHODS: A dose escalation study was performed using IntegriSense750, ProSense750EX, and ProSense750FAST in mice (n = 5) bearing luciferase-positive SCC-1flank 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. RESULTS: 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). CONCLUSION: All three agents appear effective for FGS.
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