Monitoring Pc 4-mediated photodynamic therapy of U87 tumors with dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) in the athymic nude rat

Abstract

ABSTRACT Introduction : Post-operative verification of the specificity and sensitivity of photodynamic therapy (PDT) is most pressing for deeply placed lesions such as brain tumors. We wish to determine whether Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) can provide a non-invasive and unambiguous quantitative measure of the specificity and sensitivity of brain tumor PDT. Methods : 2.5 x 10 5 U87 cells were injected into the brains of six athymic nude rats. After 5-6 days, the animals r eceived 0.5 mg/kg b.w. of the phthalocyani ne photosensitizer Pc 4 via tail-vein injection. On day 7 peri-tumor DCE-MRI images were acqui red on a 7T microMRI scanner before and after tail-vein administration of 100 P L gadolinium and 400 P L saline. After this scan th e animals received a 30 J/cm 2 dose of 672-nm light from a diode laser (i.e., PDT). The DCE-MRI scan protocol was repeated on day 13. Next, the animals were euthanized and their brains were explanted for Hematoxylin and Eosin (H&E) histology. Results : No tumor was found in one animal. The DCE-MRI images of the other five anim als demonstrated significant tumor enhancement increase ( p < 0.053 two-sided t-test and p < 0.026 one-sided t-test) following PDT. H&E histology presented moderate to severe tumor necrosis. Discussion : The change in signal detected by DCE-MRI appears to be due to PDT-induced tumor necrosis. This DCE-MRI signal appears to provide a quantitativ e, non-invasive measure of the outcome of PDT in this animal model and may be useful for determining the safety and effectiveness of PDT in deeply placed tumors (e.g., glioma). Keywords: glioma, brain cancer, necrosis, neurosurgery, PDT, photosensitizer, phthalocyanine, Gd-DTPA.