Experimental and clinical results of mTHPC (Foscan)-mediated photodynamic therapy for malignant brain tumors

摘要

Abstract: M-THPC, a second generation photosensitizer, has greater potential of phototoxicity than the first generation PS hematoporphyrinderivative because of greater light penetration depth into tissue and higher therapeutic index. The uptake, selectivity and kinetics of C-14 labeled mTHPC was investigated in a C6 glioma induced rat model. The highest amount was detected at 48 to 96 hours after intraperitoneal injection with a ratio of 150:1 of tumor to normal brain concentration (0.53 vs. 0.003 $mu@g/g tissue). A high selectivity was also confirmed by confocal laserscanning microscope in frozen sections of the human glioblastoma. Up to now 15 patients underwent mTHPC-mediated PDT presenting with primary (n equals 2), recurrent (n equals 8) glioblastoma multiform or recurrent metastatic disease of the brain (n equals 3) and of the scull base (n equals 2). After sensitization with 0.15 Foscan$+R$/ mg/kg i.v. a gross tumor removal was performed on day 4 followed by intraoperative PDT by a KTP pumped dye laser or a diode laser emitting at 652 nm (light dose of 20 J/cm$+2$/). Patients with primary glioblastomas underwent additional radiation therapy with one progressing after 5 months, the other is surviving for 6 months, patients with recurrent glioblastomas demonstrated a median time to progression of 4 months and a median survival of 6 months, patients with metastasis faired better with only one progressing after 6 months the remaining 4 patients are alive demonstrating a complete response with a median survival time of 7 months. Our first clinical results of mTHPC mediated PDT in brain tumors demonstrate that the survival time of our patients are not superior as compared to the first generation sensitizer. Due to its superior photophysical properties however, mTHPC should be intensely investigated for its use in neurosurgery. !18