PHOTODYNAMIC THERAPY OF INTRACRANIAL TISSUES - A PRECLINICAL COMPARATIVE-STUDY OF 4 DIFFERENT PHOTOSENSITIZERS

The effectiveness of four different photosensitizers for intracranial photodynamic therapy (PDT) of normal brain tissues and an intracranial tumor was investigated in rabbits, using the photodynamic threshold m odel. Summary: PDT is currently being investigated as an adjuvant trea tment to surgical resection and/or radio chemotherapy of intracranial neoplasms. While possible neurotoxic side effects of the treatment hav e been noted, only limited preclinical data quantifying the response o f intracranial normal and tumor tissues following PDT are available. M aterials and Methods: The photodynamic threshold dose values for the f our photosensitizers, Photofrin, 5-aminolevulinic acid (ALA)-induced P rotoporphyrin TX (PpIX), Tin Ethyl Etiopurpurin (SnET2), and chloroalu minum phthalocyanine (AlClPc), were determined using measured light fl uence distributions, photosensitizer concentration in tissue, and hist ologically-determined extent of necrosis following PDT. These measurem ents were made in normal rabbit brain and in an intracranially-implant ed carcinoma (VX2). Results: For Photofrin, AlClPc, and SnET2 tin an e mulsion delivery vehicle) normal grey and white matter were very sensi tive to PDT, showing a significantly lower threshold dose value than V X2-tumor. For ALA-induced PpIX and SnET2 tin liposome) very little or no white matter damage was observed. Additionally, ALA-PpIX showed sig nificantly lower concentration in white matter than in cortex and tumo r, Normal brain structures lacking a blood-brain barrier showed high u ptake of all photosensitizers and, hence, are at risk of collateral da mage during PDT. Conclusions: For clinical PDT of most adult intracran ial neoplasms ALA-induced PpIX appears to be promising, and SnET2 (lip osomal) has potential for selective tumor destruction with relative sp aring of white matter. Other normal brain structures and, for the othe r photosensitizers, also white matter are at risk of collateral damage , if exposed to light during PDT.