26 February 2008 The effect of motexafin gadolinium on ALA photodynamic therapy in glioma spheroids
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Abstract
Following surgical removal of malignant brain tumors 80% of all cases develop tumor recurrence within 2 cm of the resected margin. The aim of postoperative therapy is therefore elimination of nests of tumor cells remaining in the margins of the resection cavity. Light attenuation in tissue makes it difficult for adequate light fluences to reach depths of 1-2 cm in the resection margin making it difficult for standard intraoperative photodynamic therapy (PDT) to accomplish this goal. Thus additional agents are required that either increase the efficacy of low fluence PDT or inhibit cellular repair, to enhance effectiveness of PDT in the tumor resection cavity. Motexafin gadolinium (MGd) is one such agent previously reported to enhance the cytotoxic potential of radiation therapy, as well as several chemotherapeutic agents by causing redox stress to cancerous cells. MGd is well tolerated with tumor specific uptake in clinical studies. The authors evaluated MGd as a potential PDT enhancing agent at low light fluences using an in vitro model. Multicellular Glioma spheroids (MGS) of approximately 300 micron diameter, obtained from ACBT cell lines were subjected to acute PDT treatments at 6J, 12J, and 18J light fluences. Growth was determined by measuring diameters in two axes. At four weeks a dose dependent inhibition of spheroid growth was seen in 33%, 55%, and 83% of the MGS at 6J, 12J, and 18J respectively, while inhibition followed by a partial reversal of growth was seen in 17%, 33%, and 17% respectively. This study provides a rationale for the use of this drug as a PDT enhancer in the management of brain tumors.
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Marlon S. Mathews, Marlon S. Mathews, Rogelio Sanchez, Rogelio Sanchez, Chung-Ho Sun, Chung-Ho Sun, Steen J. Madsen, Steen J. Madsen, Henry Hirschberg, Henry Hirschberg, } "The effect of motexafin gadolinium on ALA photodynamic therapy in glioma spheroids", Proc. SPIE 6842, Photonic Therapeutics and Diagnostics IV, 68422N (26 February 2008); doi: 10.1117/12.760260; https://doi.org/10.1117/12.760260
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