Isao Sakata

Mechanism of photodynamic therapy (PDT): investigation of sensitizer dose and light dose-rate effects

The thresholds in sensitizer concentration and in light dose rate for PDT effects have been examined on the basis of a chemical reaction. The examination revealed that there exists basically no thresholds of drug and light dose-rate effects in PDT, but apparently there does. Also it was suggested that PDT effects depend largely on peak power of laser and not so largely on the total joule. And for PDT the use of pulse laser with relatively high peak power is better than the use of the lower one, especially cw laser.

Boron-, Gadolinium-Porphyrin Derivatives for Neutron Capture Therapy

New porphyrin derivatives conjugated with boron(B) or gadolinium(Gd) were developed to use as compound for neutron capture therapy in order to obtain tumor selective accumulation of B or Gd. In neutron capture therapy, it is essential to know the B or Gd distribution in the tumor and in the normal brain. Using sodium borocaptate (BSH), detection of the boron concentration in the tumor and blood before the therapy require operative sampling and additional analysis such as inductively coupled plasma (ICP) analysis (1) and still the intratumoral heterogeneity of B distribution can not be analyzed precisely. Our study was aimed to develop B or Gd compounds for neutron capture therapy which could be visualized on MRI. This compound enables preoperative evaluation of the spatial distribution of B or Gd and its clearance from the tissue without operative samplings. Such porphyrin derivatives are thought to be useful in neutron capture therapy.

Combined effects of photodynamic and sonodynamic treatment on experimental skin cancer on C3H mice

In recent years, the effect of ultrasound (US) in combination with porphyrins such as a gallium-porphyrin complex (ATX-70) has been reported in the treatment of experimental cancers. Before clinical application of this method, further studies are needed. The transplanted squamous cell carcinomas (5CC) on C3H/He mice were irradiated by a tunable optical parametric oscillator (OPO) laser light or ultrasound, in the presence of several different photosensitizers. The tumor size and survival of mice after treatment were observed. Furthermore, we compared antitumor effects of combined irradiation of laser light and ultrasound with those of single laser light or ultrasound, in the presence of ATX-70 or a pheoforbide derivative (PH-1126). Besides PH-i 126 and ATX-70, the following sensitizers were tested: Photofrin II (Pf-II), hematoporphyrin oligomer (HpO). 5-aminolevulinic acid (5-ALA) and aluminum phthalocyanine tetrasuiphonate (AIPcS4). In the results, it was good effects of antitumor by the laser light treatment in the case of PH-1126 and AIPcS4, ATX-70, HpO nsd AIPcS4 produced betterantitumor effeets by irradiation with ultrasound. The antitumor effects of combined use of laser fight and ultrasound were stronger than those of single laser light or ultrasound in both cases of PH-i 126 and ATX-70. Key words: OPO laser light, ultrasound, PH-1126. ATX-70

Acoustic, fluorescent diagnosis of malignant lesions using HAT-D01 and ATX-S10

We have synthesized approximately 700 kinds of porphyrin derivatives and studied their side chain structures and affinities for tumor tissues. On the basis of these studies, a tumor localizing photo-chlorine photosensitizer named ATX-S10 has been synthesized for PDT and fluorescent diagnosis of malignant lesions. A non-photosensitive fluorescent diagnostic agent named HAT-D01 has also been synthesized. Both derivatives have the fluorescence near 680 nm that is far from the auto-fluorescence of biological tissue. For detection of tumor tissue, we have developed a new device that can pick up 670 - 680 nm fluorescence selectively and convert the intensity of fluorescence to the sound. By using this simple new device after ATX- S10, HAT-D01 administration we could detect well the malignant lesions.

Cell Cycle Change of 9L Glioma Cell after in Vitro Boron Neutron Capture Therapy

Proliferating tumor cell progress through the phases of each cell cycle. Cell cycle change such as G2/M arrest is known to occur in tumor cells after γ ray radiation.1,2 However, cell cycle change of tumor cell after neutron capture therapy has not been reported. We irradiated thermal neutron to 9L gliosarcoma cell in vitro with or without boron compounds and examined cell cycle changes of tumor cells with flow cytometry.