ALA-PDT of glioma cell micro-clusters in BD-IX rat brain

Steen J. Madsen; Even Angell-Petersen; Signe Spetalen; Stephen W. Carper; Sarah A Ziegler; Henry Hirschberg M.D.

doi:10.1117/12.648969

22 February 2006 ALA-PDT of glioma cell micro-clusters in BD-IX rat brain

Steen J. Madsen, Even Angell-Petersen, Signe Spetalen, Stephen W. Carper, Sarah A Ziegler, Henry Hirschberg M.D.

Proceedings Volume 6078, Photonic Therapeutics and Diagnostics II; 60782Y (2006) https://doi.org/10.1117/12.648969
Event: SPIE BiOS, 2006, San Jose, California, United States

Abstract

A significant contributory factor to the poor prognosis of patients with glioblastoma multiforme is the inability of conventional treatments to eradicate infiltrating glioma cells. A syngeneic rat brain tumor model is used to investigate the effects of aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) on small clusters of tumor cells sequestered in normal brain. The intrinsic sensitivity of rat glioma cells to PDT was investigated by exposing ALA-incubated cells to a range of radiant exposures and irradiances using 635 nm light. Biodistribution studies were undertaken on tumor-bearing animals in order to determine the tumor selectivity of the photosensitizer following systemic administration (i.p.) of ALA. Effects of ALA-PDT on normal brain and gross tumor were evaluated using histopathology. Effects of PDT on isolated glioma cells in normal brain were investigated by treating animals 48 h after tumor cell implantation: a time when the micro-clusters of cells are protected by an intact blood-brain-barrier (BBB). Rat glioma cells in monolayer are susceptible to ALA-PDT - lower irradiances are more effective than higher ones. Fluorescence microscopy of frozen tissue sections showed that photosensitizer is produced with better than 200:1 tumor-to-normal tissue selectivity following i.p. ALA administration. ALA-PDT resulted in significant damage to both gross tumor and normal brain, however, the treatment failed to prolong survival of animals with newly implanted glioma cells compared to non-treated controls if the drug was delivered either i.p. or directly into the brain. In contrast, animals inoculated with tumor cells pre-incubated in vitro with ALA showed a significant survival advantage in response to PDT.

Citation Download Citation

Steen J. Madsen, Even Angell-Petersen, Signe Spetalen, Stephen W. Carper, Sarah A Ziegler, and Henry Hirschberg M.D. "ALA-PDT of glioma cell micro-clusters in BD-IX rat brain", Proc. SPIE 6078, Photonic Therapeutics and Diagnostics II, 60782Y (22 February 2006); https://doi.org/10.1117/12.648969

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KEYWORDS

Tumors

Brain

Photodynamic therapy

Blood brain barrier

Luminescence

Toxicity

Control systems

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