PMID- 27793401 OWN - NLM STAT- MEDLINE DCOM- 20170406 LR - 20240425 IS - 1552-6259 (Electronic) IS - 0003-4975 (Print) IS - 0003-4975 (Linking) VI - 103 IP - 2 DP - 2017 Feb TI - Near-Infrared Intraoperative Molecular Imaging Can Locate Metastases to the Lung. PG - 390-398 LID - S0003-4975(16)31147-X [pii] LID - 10.1016/j.athoracsur.2016.08.079 [doi] AB - BACKGROUND: Pulmonary metastasectomy is widely accepted for many tumor types because it may prolong survival and potentially cure some patients. However, intraoperative localization of pulmonary metastases can be technically challenging. We propose that intraoperative near-infrared (NIR) molecular imaging can be used as an adjunct during disease localization. METHODS: We inoculated 50 C57BL/6 mice with Lewis lung carcinoma (LLC) flank tumors. After flank tumor growth, mice were injected through the tail vein with indocyanine green (ICG) before operation, and intraoperative imaging was used to detect pulmonary metastases. On the basis of these experiments, we enrolled 8 patients undergoing pulmonary metastasectomy into a pilot and feasibility clinical trial. Each patient received intravenous ICG 1 day before operation, followed by wedge or segmental resection. Samples were imaged on the back table with an NIR camera to confirm disease presence and margins. All murine and human tumors and margins were confirmed by pathologic examination. RESULTS: Mice had an average of 4 +/- 2 metastatic tumors on both lungs, with an average size of 5.1 mm (interquartile range [IQR] 2.2 mm to 7.6 mm). Overall, 200 of 211 (95%) metastatic deposits were markedly fluorescent, with a mean tumor-to-background ratio (TBR) of 3.4 (IQR 3.1 to 4.1). The remaining tumors had a TBR below 1.5. In the human study, intraoperative NIR imaging identified six of the eight preoperatively localized lesions. Intraoperative back table NIR imaging identified all metastatic lesions, which were confirmed by pathologic examination. The average tumor size was 1.75 +/- 1.4 cm, and the mean ex vivo TBR was 3.3 (IQR 3.1 to 3.7). Pathologic examination demonstrated melanoma (n = 4), osteogenic sarcoma (n = 2), renal cell carcinoma (n = 2), chondrosarcoma (n = 1), leiomyosarcoma (n = 1), and colorectal carcinoma (n = 1). CONCLUSIONS: Systemic ICG identifies subcentimeter tumor metastases to the lung in murine models, and this work provides proof of principle in humans. Future research is focused on improving depth of penetration into the lung parenchyma. CI - Copyright (c) 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved. FAU - Keating, Jane AU - Keating J AD - Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania; Center for Precision Surgery, Abramson Cancer Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania. FAU - Newton, Andrew AU - Newton A AD - Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania; Center for Precision Surgery, Abramson Cancer Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania. FAU - Venegas, Ollin AU - Venegas O AD - Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania; Center for Precision Surgery, Abramson Cancer Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania. FAU - Nims, Sarah AU - Nims S AD - Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania; Center for Precision Surgery, Abramson Cancer Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania. FAU - Zeh, Ryan AU - Zeh R AD - Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania; Center for Precision Surgery, Abramson Cancer Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania. FAU - Predina, Jarrod AU - Predina J AD - Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania; Center for Precision Surgery, Abramson Cancer Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania. FAU - Deshpande, Charuhas AU - Deshpande C AD - Department of Pathology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania. FAU - Kucharczuk, John AU - Kucharczuk J AD - Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania; Center for Precision Surgery, Abramson Cancer Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania. FAU - Nie, Shuming AU - Nie S AD - Departments of Biomedical Engineering and Chemistry, Emory University, Atlanta, Georgia. FAU - Delikatny, E James AU - Delikatny EJ AD - Department of Radiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania. FAU - Singhal, Sunil AU - Singhal S AD - Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania; Center for Precision Surgery, Abramson Cancer Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania. Electronic address: sunil.singhal@uphs.upenn.edu. LA - eng GR - R01 CA163256/CA/NCI NIH HHS/United States GR - R01 CA193556/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20161025 PL - Netherlands TA - Ann Thorac Surg JT - The Annals of thoracic surgery JID - 15030100R SB - IM CIN - Ann Thorac Surg. 2018 Mar;105(3):988-989. PMID: 29455813 CIN - Ann Thorac Surg. 2018 Mar;105(3):989. PMID: 29455815 MH - Animals MH - Feasibility Studies MH - Female MH - Humans MH - Intraoperative Period MH - Lung Neoplasms/diagnosis/*secondary/surgery MH - Mice MH - Mice, Inbred C57BL MH - Molecular Imaging/*methods MH - Neoplasm Metastasis MH - *Neoplasms, Experimental MH - Pilot Projects MH - Pneumonectomy/*methods MH - Retrospective Studies MH - Spectroscopy, Near-Infrared/*methods PMC - PMC11024498 MID - NIHMS1980101 EDAT- 2016/10/30 06:00 MHDA- 2017/04/07 06:00 PMCR- 2024/04/18 CRDT- 2016/10/30 06:00 PHST- 2016/01/24 00:00 [received] PHST- 2016/08/16 00:00 [revised] PHST- 2016/08/17 00:00 [accepted] PHST- 2016/10/30 06:00 [pubmed] PHST- 2017/04/07 06:00 [medline] PHST- 2016/10/30 06:00 [entrez] PHST- 2024/04/18 00:00 [pmc-release] AID - S0003-4975(16)31147-X [pii] AID - 10.1016/j.athoracsur.2016.08.079 [doi] PST - ppublish SO - Ann Thorac Surg. 2017 Feb;103(2):390-398. doi: 10.1016/j.athoracsur.2016.08.079. Epub 2016 Oct 25.