title: Intraoperative Molecular Diagnostic Imaging Can Identify Renal Cell Carcinoma.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: Thomas.Guzzo@uphs.upenn.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Guzzo
authors.affiliation: Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Jack
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Jane
authors.initials: J
authors.lastname: Keating
authors.affiliation: Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: DeJesus
authors.affiliation: Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Ryan
authors.initials: R
authors.lastname: Judy
authors.affiliation: Department of Biomedical Engineering and Chemistry, Emory University, Atlanta, Georgia.
authors.forename: Shuming
authors.initials: S
authors.lastname: Nie
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, Indiana.
authors.forename: Philip
authors.initials: P
authors.lastname: Low
authors.affiliation: Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Priti
authors.initials: P
authors.lastname: Lal
authors.affiliation: Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Sunil
authors.initials: S
authors.lastname: Singhal
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000601:surgery*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007430:Intraoperative Care; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000601:surgery*; D008297:Male; D051379:Mice; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D057054:Molecular Imaging; D009368:Neoplasm Transplantation; D009392:Nephrectomy; D010865:Pilot Projects
keywords: carcinoma; fluorescein isothiocyanate; kidney; molecular imaging; nephrectomy; renal cell