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Sensitive in vivo Visualization of Breast Cancer Using Ratiometric Protease-activatable Fluorescent Imaging Agent,

Marcel Miampamba1, Junjie Liu1, Alec Harootunian1

  • 1Avelas Biosciences, 11099 N. Torrey Pines Road, Suite 290, La Jolla, CA, USA.

Theranostics
|September 14, 2017
PubMed
Summary

A new fluorescent dye, AVB-620, effectively highlights cancerous tissue for improved intraoperative visualization. This novel agent demonstrates high sensitivity and specificity in detecting breast cancer metastases and differentiating tumor from healthy tissue.

Keywords:
Breast canceractivatable cell penetrating peptidefluorescence-guided surgeryimagingmatrix metalloproteinase.

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Area of Science:

  • Oncology
  • Medical Imaging
  • Biochemistry

Background:

  • Improving intraoperative cancer visualization is crucial for effective surgical treatment.
  • Current methods for detecting cancerous tissue during surgery have limitations.

Purpose of the Study:

  • To develop and evaluate AVB-620, a novel fluorescent peptide dye conjugate for enhanced intraoperative cancer visualization.
  • To assess the diagnostic performance of AVB-620 in preclinical models and human tissue samples.

Main Methods:

  • AVB-620 is an intravenously administered fluorescent dye activated by matrix metalloproteinases (MMPs).
  • Diagnostic performance was evaluated in syngeneic mouse models for breast cancer lymph node metastases.
  • An in vitro study assessed AVB-620's ability to differentiate human breast cancer from healthy tissue.

Main Results:

  • AVB-620 demonstrated high in vivo diagnostic sensitivity and specificity (>95%) for identifying breast cancer metastases in mouse models.
  • In vitro studies showed AVB-620 had 2-3 fold faster hydrolysis in human tumor tissue compared to healthy tissue, yielding 96% sensitivity and 88% specificity.
  • Toxicology studies in rats indicated a favorable safety profile with a no-observed-adverse-effect-level (NOAEL) significantly above the estimated human dose.

Conclusions:

  • AVB-620 is a promising agent for improving intraoperative cancer detection, particularly for breast cancer.
  • The dye exhibits excellent sensitivity and specificity in both preclinical models and human tissue.
  • AVB-620's optimized pharmaceutical properties and safety profile support its advancement into clinical trials.