Preclinical Validation of the Utility of BLZ-100 in Providing Fluorescence Contrast for Imaging Spontaneous Solid Tumors

Cancer Res. 2015 Oct 15;75(20):4283-91. doi: 10.1158/0008-5472.CAN-15-0471.

Abstract

There is a need in surgical oncology for contrast agents that can enable real-time intraoperative visualization of solid tumors that can enable complete resections while sparing normal surrounding tissues. The Tumor Paint agent BLZ-100 is a peptide-fluorophore conjugate that can specifically bind solid tumors and fluoresce in the near-infrared range, minimizing light scatter and signal attenuation. In this study, we provide a preclinical proof of concept for use of this imaging contrast agent as administered before surgery to dogs with a variety of naturally occurring spontaneous tumors. Imaging was performed on excised tissues as well as intraoperatively in a subset of cases. Actionable contrast was achieved between tumor tissue and surrounding normal tissues in adenocarcinomas, squamous cell carcinomas, mast cell tumors, and soft tissue sarcomas. Subcutaneous soft tissue sarcomas were labeled with the highest fluorescence intensity and greatest tumor-to-background signal ratio. Our results establish a foundation that rationalizes clinical studies in humans with soft tissue sarcoma, an indication with a notably high unmet need.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Animals
  • Child
  • Child, Preschool
  • Contrast Media* / administration & dosage
  • Diagnostic Imaging / instrumentation
  • Diagnostic Imaging / methods*
  • Disease Models, Animal
  • Dogs
  • Female
  • Fluorescent Dyes* / administration & dosage
  • Humans
  • Indocyanine Green / administration & dosage
  • Indocyanine Green / analogs & derivatives
  • Intraoperative Care
  • Male
  • Neoplasms / diagnosis*
  • Neoplasms / pathology
  • Reproducibility of Results
  • Scorpion Venoms / administration & dosage

Substances

  • Contrast Media
  • Fluorescent Dyes
  • Scorpion Venoms
  • tozuleristide
  • Indocyanine Green