Photodynamic therapy in malignant brain tumour: Is intratumoral injection of photosensitizer superior to conventional intravenous administration?

Abstract

Objective: Selective uptake and retention of haematoporphyrin derivative (HpD) in tumour tissue, especially at brain adjacent to the tumour (BAT) region, is an important factor in determining the efficacy of photodynamic therapy (PDT). The uptake and distribution of HpD was studied in 10 patients with malignant glioma. Method: Five cases were injected with HpD intravenously at a dose of 5mg/kg bodyweight. Another five cases were injected with 10mg (2mL) HpD by ultrasound guidance into the tumour centre. After 24h, the patients underwent craniotomy for tumour debulking. Biopsies of the tumour tissue and BAT region were sent for analysis. Results: In the intravenous administration group, the mean HpD level in the tumour centre was 2.0±0.7 μg/g, which was lower than the level of HpD in the BAT region (3.6±2.3μg/g; P>0,05). However, in the intratumoral injection group, the level of HpD was much higher in the tumour centre than in the BAT (4.7±3.2μg/g vs 1.4±0.4 μg/g; P<0.05). Fluorescence microscopy observations showed that HpD was distributed unevenly at the periphery of the blood vessels and stroma in the intravenous group. Bright and patchy distribution of HpD was also seen in the tumour centre after direct intratumoral injection. Intracellular uptake of HpD could be observed in the BAT region of both groups. Further study with a confocal laser scanning microscope (CLSM) provided evidence that HpD was localized intracellularly. Conclusion: The study showed that conventional intravenous administration of HpD can achieve a higher level in the BAT region, but the distribution of HpD varied and was unpredictable. Intratumoral injection can achieve a much higher HpD in the tumour centre; however, the distribution in the BAT region is unsatisfactory because of the irregular shape of the tumour mass. Taking into account this variable result, the HpD level may need to be tailored to meet each individual patient's requirement.