Intraoperative 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, Sunil Singhal

Research output: Contribution to journalArticle

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)748-755
Number of pages8
JournalJournal of Urology
Volume195
Issue number3
DOIs
StatePublished - 2016

Keywords

  • carcinoma
  • fluorescein isothiocyanate
  • kidney
  • molecular imaging
  • nephrectomy
  • renal cell

ASJC Scopus subject areas

  • Urology

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