Microendoscopy for hypericin fluorescence tumor diagnosis in a subcutaneous glioma mouse model

Photodiagnosis Photodyn Ther. 2013 Dec;10(4):552-60. doi: 10.1016/j.pdpdt.2013.06.001. Epub 2013 Jul 11.

Abstract

Background: New treatment strategies for malignant gliomas are indispensible, due to the poor prognosis for patients. Fluorescence diagnosis (FD) and photodynamic therapy (PDT) are currently under intensive investigation and seem to improve the prognosis. Especially for deep seated malignant brain lesions and in order to optimize therapy new diagnostic tools are needed.

Methods: In a syngeneic subcutaneous glioma mouse model we investigated the time dependent hypericin (HYP) uptake in malignant tumor tissue by microendoscopically fluorescence measurements. The HYP fluorescence in tumor was also detected by fluorescence microscopy (FM) and was compared to endoscopic data.

Results: Both methods, microendoscopy and FM, demonstrated time dependent HYP uptake in subcutaneously implanted mouse glioma. Maximum of HYP uptake was achieved after 6h, measured with both methods. FM reached a 10-fold increase in fluorescence intensity compared to the autofluorescence. Measured by microendoscopy a 2.2-fold HYP fluorescence intensity compared to the autofluorescence was detected. Microendoscopy enables visualization of small vessels even in healthy brain tissue by intravascular HYP fluorescence.

Conclusion: The new developed microendoscope enables not only fluorescence based discrimination of tumor and healthy tissue, but also semiquantitative measurements of fluorescence intensities in vivo. Individual repetitive fluorescence diagnosis will become possible by this method and opens up new possibilities for determining optimal settings of light applications for PDT.

Keywords: Fluorescence visualization; Glioma; Hypericin; Microendoscope; Photodiagnosis.

MeSH terms

  • Animals
  • Anthracenes
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Disease Models, Animal*
  • Endoscopy / methods*
  • Glioma / metabolism*
  • Glioma / pathology*
  • Metabolic Clearance Rate
  • Mice
  • Perylene / analogs & derivatives
  • Perylene / pharmacokinetics
  • Photosensitizing Agents / pharmacokinetics
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Spectrometry, Fluorescence / methods*
  • Tissue Distribution

Substances

  • Anthracenes
  • Photosensitizing Agents
  • Perylene
  • hypericin