Intraoperative Molecular Diagnostic Imaging Can Identify Renal Cell Carcinoma

No AccessJournal of UrologyInvestigative Urology1 Mar 2016Intraoperative Molecular Diagnostic Imaging Can Identify Renal Cell Carcinoma Thomas J. Guzzo, Jack Jiang, Jane Keating, Elizabeth DeJesus, Ryan Judy, Shuming Nie, Philip Low, Priti Lal, and Sunil Singhal Thomas J. GuzzoThomas J. Guzzo Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania More articles by this author , Jack JiangJack Jiang Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania More articles by this author , Jane KeatingJane Keating Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania More articles by this author , Elizabeth DeJesusElizabeth DeJesus Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania More articles by this author , Ryan JudyRyan Judy Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania More articles by this author , Shuming NieShuming Nie Department of Biomedical Engineering and Chemistry, Emory University, Atlanta, Georgia More articles by this author , Philip LowPhilip Low Department of Chemistry, Purdue University, West Lafayette, Indiana More articles by this author , Priti LalPriti Lal Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania More articles by this author , and Sunil SinghalSunil Singhal Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.09.093AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Margin status can often be difficult to assess intraoperatively, particularly during partial nephrectomy given the time constraints related to renal hilar clamping. We hypothesized that a targeted molecular imaging approach could be used during surgery to identify tumor margins and confirm disease clearance. Materials and Methods: EC17, a novel tracer targeting FRα, was used in murine models of renal cell carcinoma to identify positive margins after surgery. Positive margins were detected due to elevated tumor-to-background ratios of the tumor compared to surrounding normal tissues. We performed a pilot study in 4 patients using EC17 preoperatively with intraoperative imaging during the operation. Results: FRα was highly expressed in 65% of clear cell renal cell carcinomas harvested from the operating room. In the murine model intraoperative imaging of renal cell carcinoma revealed a mean ± SD tumor-to-background ratio of 8.2 ± 1.1 in the RCC10, 11.2 ± 1.1 in the 786-0 and 4.3 ± 1.1 in the UMRC2 cell line. Compared to visual inspection intraoperative imaging of the surgical resection bed identified residual disease in 24% more animals. In the human pilot study targeted molecular imaging identified 2 of 4 renal cell carcinomas and had no false-positive results. In these 2 cases the tumor-to-background ratio was 3.7 and 4.6, respectively. In each case we confirmed disease clearance and tumor fluorescence did not correlate with nodule size or tumor grade. Conclusions: To our knowledge this is the first demonstration in humans of identifying renal cell carcinoma during surgery using a targeted molecular contrast agent. This approach may lead to a superior method of identifying malignancy and tumor borders in the intraoperative setting. References 1 : Cancer statistics, 2014. CA Cancer J Clin2014; 64: 9. Google Scholar 2 : Surgeons' preferences and practice patterns regarding intraoperative frozen section during partial nephrectomy. Urol Oncol2014; 32: 864. Google Scholar 3 : Nanotechnology applications in surgical oncology. Annu Rev Med2010; 61: 359. 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Volume 195Issue 3March 2016Page: 748-755 Advertisement Copyright & Permissions© 2016 by American Urological Association Education and Research, Inc.Keywordsnephrectomykidneyrenal cellfluorescein isothiocyanatecarcinomamolecular imagingAcknowledgmentsDr. M. Celeste Simon, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, assisted with data preparation and provided the cell lines 786-0, UMRC2, A498 and RCC10.MetricsAuthor Information Thomas J. Guzzo Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania More articles by this author Jack Jiang Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania More articles by this author Jane Keating Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania More articles by this author Elizabeth DeJesus Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania More articles by this author Ryan Judy Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania More articles by this author Shuming Nie Department of Biomedical Engineering and Chemistry, Emory University, Atlanta, Georgia More articles by this author Philip Low Department of Chemistry, Purdue University, West Lafayette, Indiana More articles by this author Priti Lal Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania More articles by this author Sunil Singhal Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania More articles by this author Expand All Advertisement PDF downloadLoading ...