Administration Of Hematoporphyrin Derivative Research Articles

Acute skin response in albino mice following porphyrin photosensitization under oxic and anoxic conditions.

Abstract Acute normal skin toxicity induced by porphyrin photosensitization has been examined using albino mice. Oxic and anoxic (clamped) skin was exposed to red light (630 nm) 24 h following administration of hematoporphyrin derivative (HpD) or Photofrin II (the active component of HpD). Experiments were also performed to determine the effect of sodium pentobarbital anesthesia on HpD and Photofrin II photosensitization of normal skin. Results from this study demonstrated that comparable levels of acute skin damage were induced by HpD and Photofrin II under oxic conditions but neither porphyrin produced any apparent phototoxicity under anoxic conditions. In addition, the level of skin damage induced by porphyrin photosensitization was not affected by sodium pentobarbital anesthesia.

Hematoporphyrin photoradiation therapy for iris neovascularization. A preliminary report.

Photoradiation therapy is a new technique currently under clinical investigation for the treatment of a variety of solid malignant tumors. The technique involves intravenous (IV) administration of hematoporphyrin derivative, a photosensitizing compound that is preferentially retained by malignant cells, and photoactivation of a neoplasm with red light (630 nm) to obtain selective destruction of cancer cells. A modification of this technique was used to treat iris neovascularization produced in a primate model of retinal vein occlusion. Following IV injection of hematoporphyrin derivative, the anterior surface of the iris was exposed to red light for 30 to 45 minutes. In the four eyes treated, there was a marked reduction of fluorescein leakage from the neovascular tissue within 24 hours following treatment. Histologic examination of two eyes demonstrated a selective response of the iris neovascularization to this therapy, with apparent preservation of surrounding tissue.

Laser phototherapy following HpD administration in superficial neoplastic lesions.

We report our preliminary clinical experience with hematoporphyrin derivative (HpD) injection and argon or dye laser irradiation for the treatment of 61 surface neoplastic lesions in 7 patients. Forty-three sites were multiple basal cell carcinoma in 5 patients, and the remaining 18 were cutaneous and subcutaneous recurrent breast carcinoma after mastectomy in the thoracic wall. The patients were selected on the basis of the lack of indication for conventional therapeutic modalities. The selection of irradiation procedures and laser source was based on the thickness of the lesion and extension of the disease. The photochemical reaction between HpD injected i.v. at a dose of 3 mg/kg body weight and the laser beam at a dose of 60 to 120 J/cm2 resulted in 75% favorable responses at the treated sites. Optimal therapeutic effects appeared to be critically dependent on total light dose and tumor infiltration patterns. The phototherapeutic technique proved to be effective in selected cases of neoplastic lesions, especially when conventional treatment modalities were poorly indicated or contraindicated.

Cystoscopic Fluorescence Detector for Photodetection of Bladder Carcinoma with Hematoporphyrin Derivative

Hematoporphyrin derivative, a fluorngenic substance, tends to accumulate at higher levels in most tumor tissues after intravenous injection. These properties provide a potential application for the detection of malignant tumors. We report the development and in vitro evaluation of an instrument designed to excite and detect low levels of hematoporphyrin derivative fluorescence emitted tumor cells in the bladder after hematoporphyrin derivative administration. The light source of the instrument for specific hematoporphyrin derivative excitation is at a wavelength of 405 nanometers. Optical fibers for both the excitation and detection of fluorescence were bundled in a single 7 French ureternl catheter which can be inserted into a standard cystoscope. The fluorescence is initially detected as an electrical signal which is amplified and then converted into an audio signal. The interference of the cystoscope illuminating white light to the fluorescence signal is eliminated by a phase-sensitive electronic circuit. The instrument thus allows simultaneous viewing of the bladder and detection of hematoporphyrin derivative fluorescence produced from tumor tissues. In vitro testings using hematoporphyrin derivative solutions on filter paper indicated that the instrument detects as little as 30 nanograms per milliliter of hematoporphyrin derivative and has relatively low noise levels from normal tissues. The utility of this instrument for hematoporphyrin derivative photodetection of small tumors and carcinoma in situ in bladder is currently under clinical evaluation.

Hematoporphyrin derivative and photoradiation therapy in early stage lung cancer.

Photoradiation therapy (PRT) with administration of hematoporphyrin derivative (HPD) was performed in ten cases of early stage central-type lung cancer of which six cases were treated by PRT alone due to inoperability because of poor pulmonary function in five and refusal of surgery in one. Four cases were resected after PRT. In the former, complete tumor remission was obtained in all six and in the latter, complete tumor remission was seen in one and significant remission in three. In the nonresected cases four cases are disease-free at 17-41 months and the remaining two cases died of chronic obstructive lung disease and cerebral infarction 16 and 31 months after PRT, respectively. The resected cases are disease-free 7-32 months after surgery. Indications of PRT in early stage lung cancer are discussed according to histological findings of resected specimen.

Effectiveness of laser photoradiation therapy following hematoporphyrin derivative administration in the experimental MS-2 tumor model.

The effectiveness of laser photoradiation therapy with hematoporphyrin derivative sensitization was tested in the MS-2 sarcoma. This solid tumor, transplanted into the pad of the hind leg of BALB/c mice, was found to be a sensitive experimental model for a quantitative evaluation of response to phototherapy and for determination of critical parameters in laser phototherapy treatment. Under our experimental conditions, optimal therapeutic effects appeared to be critically dependent on drug dose, number of treatments, light intensity, and irradiation of the peripheral border of the tumor.

Hematoporphyrin Derivative and Laser Photoradiation in the Treatment of Lung Cancer

Photoradiation therapy (PRT) was performed in 13 lung cancer cases and in one case of severely atypical squamous metaplasia following administration of hematoporphyrin derivative (HpD). The HpD is activated by visible red light (630 nm, 90 to 400 mW) from an argon dye laser. The cytocidal effects were due to the activation of the HpD, since 400 mW of power has in itself no effect on normal epithelium, even with long-term exposure. HpD is retained longer by malignant tissue than by normal tissue. Therefore, the lesions were irradiated with the red laser beam, delivered by a quartz fiber inserted through the instrumentation channel of the fiberoptic bronchoscope, 48 hours or more after intravenous injection of 2.5 to 4.0 mg/kg of HpD. A total of 14 cases received PRT. In one, two small, smooth-surfaced, squamous cell carcinoma tumors in the right B2b of a 74-year-old man who had refused surgery disappeared three days after HpD-photoradiation, and the patient remained disease-free 16 months after the treatment. In 12 cases of centrally located lung cancer local effects were obtained in all. However, there was no significant improvement in survival, attributable to the fact that all were advanced-stage cases. One patient with severely atypical squamous metaplasia requested treatment, and complete disappearance of metaplastic atypic was obtained.

肺癌に対するレーザー照射后の病理組織学的検討

We have been performing endoscopic suergery, in which the Nd-YAG laser is irradiated under bronchofiber scopic observation, or the therapy by argon dye laser photoirradiation combined with the administration of hematoporphyrin derivative (HpD) on patients with lung cancer since 1980. After the laser photoirradiation, the exposed lung cancer cells show degeneration, necrosis and fibrosis. These changes were histopathologically compared using biopsy specimens obtained under bronchoscopic observation and opration specimens. The tissue specimens were examined primarily concerning chages in the bronchial wall according to the criteria for the evaluation of effects of the conservative treatment suggested by Oboshiand Shimosato (Grades 0 to IV).The determination of the histopathological changes occurring in lung cancer following laser photoirradiation proved helpful to the improvement of the irradiation conditions and methods.