Photodynamic Molecular Beacons: An Image-Guided Therapeutic Approach to Breast Cancer Vertebral Metastases

Abstract

The vertebral column is the most common site of breast cancer metastases, where overexpression of matrix metalloproteinases (MMPs)promotes the spread of cancer. Current therapies for managing vertebral metastases have significant limitations due to high associated risk of spinal cord damage. An attractive alternative is photodynamic therapy (PDT) providing non-invasive and site-selective treatment. However, current photosensitizers are limited by their non-specific accumulation. Photodynamic molecular beacons (PPMMPB), activated by MMPs, offer another level of PDT selectivity and image-guidance preserving criticial tissues, specifically the spinal cord. In vitro studies confirm the specific activation of PPMMPB in MT-1 cells. In vivo experiments demonstrate specific activation of PPMMPB in MT-1 xenografts, using systemic and intratumoral injections. Using a clinically-relevant metastatic model, fluorescent imaging confirmed the specific activation of PPMMPB by vertebral metastases. As a first step, we validate that the metastasis-selective mechanism of PPMMPBs can specifically image breast cancer vertebral metastases, thereby differentiating tumor and healthy tissue. Preliminary PPMMPB - PDT results demonstrate the specific PDT induced destruction of vertebral metastases while the spinal cord is left undamaged.

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Document Details

Document Type
Technical Report
Publication Date
Mar 01, 2011
Accession Number
ADA542173

Entities

People

  • Tracy Liu

Organizations

  • University Health Network

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Anesthesia
  • Biological Sciences
  • Bone And Bones
  • Bone Diseases
  • Breast Cancer
  • Chemical Synthesis
  • Chemistry
  • Confocal Microscopy
  • Detectors
  • Health Services
  • Laser Therapy
  • Osteogenesis
  • Peptides
  • Spinal Cord
  • Spine
  • Surgery

Readers

  • Chemistry (specifically Chemical Fluorescence)
  • Medical Imaging.
  • Molecular Biology and Genetics