Interstitial light application for photodynamic therapy in a rat brain tumor model

Abstract

The usefulness of repetitive ALA mediated PDT is being evaluated in a rat brain tumor model. In preliminary experiments an optical fiber was repeatedly introduced directly into the brain to apply light, requiring multiple surgical procedures. In an attempt to refine the animal model, an indwelling light applicator, using a modified microdialysis guide cannula has been developed. The cannula is fixed to the scull and can remain in the rat brain for several weeks without complications. In studies of repetitive PDT the need for repeated mounting in a stereotactic frame and surgical procedures can be eliminated. The applicator also makes it feasible to employ low fluence rates with long treatment times, which correspond to future clinically relevant protocols. The fluence rate distribution was measured in vivo and compared to diffusion theory and Monte Carlo simulations to estimate the tissue optical properties of the rat brain for light at 632 nm. The modeling suggested a reduced scattering coefficient 38 cm -1 , an absorption coefficient 0.46 cm -1 and a penetration depth 0.14 cm.

Determination of fluence rate and temperature distributions in the rat brain; implications for photodynamic therapy

“…͑A preliminary analysis of the results from two of the rats was published in a previous report. 36 ͒ Interand intraanimal variation was of similar magnitude. As seen from the data series in the diagrams in Fig.…”

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

“…The high degree of fluorescence observed in both human and experimental glial tumors following ALA administration indicates that the level of PpIX in gross tumor tissue is probably sufficient for efficient PDT [6][7][8] . The high drug levels observed in gliomas are likely due to passive diffusion across a compromised BBB.…”

Minimally Invasive Photodynamic Therapy (PDT) for Ablation of Experimental Rat Glioma

“…Absorption and reduced scattering coefficients of 0.65 cm ± 1 and 29 cm −1 for normal brain, and 1.6 cm ± 1 and 6.9 cm ± 1 for tumor tissue, were used in the si− mulations. These tissue optical parameters were calculated from direct in vivo measurements of fluence rate in the model used here [18].…”

“…Recent publications employing mathematical models of glioma growth and invasion have point− ed out some of the reasons for the inadequacies of current ther− apy, and that even large−scale treatment−induced destruction or surgical removal of the central portion of a rapidly growing tu− mor does not translate into a dramatic increase in survival [38,39]. Different ablation treatment strategies will likely be re− quired to achieve improved survival, e. g., the use of multiple fractionated long−term treatment protocols implemented by the use of implanted light applicators and portable lasers [8,18,40,41].…”