PHOTOBLEACHING OF PORPHYRINS USED IN PHOTODYNAMIC THERAPY AND IMPLICATIONS FOR THERAPY

Abstract— The development of an extraction procedure to quantitate dihematoporphyrin ether (DHE) concentration in tissues correlated to fluorescence measurements from instrumentation developed for in vivo fluorimetry was examined. In vivo fluorometric results from mouse mammary carcinoma (SMT‐F) were calibrated against results of the chemical extraction assay quantitated spectrophotometrically. Fluorescence and drug extractable levels increase in a linear fashion with injected dose. Loss of porphyrin fluorescence (photobleaching) and intra‐tumoral porphyrin level has been demonstrated both in vitro (NHIK cells) and in vivo (SMT‐F tumor) during illumination with light following exposure to Hpd or DHE. This process is essentially independent of porphyrin tumor level in vivo and could lead to tumor protection at very low porphyrin levels. On the other hand, this photobleaching process which occurs concurrent with cellular inactivation and tissue damage due to the photodynamic process can be exploited to protect normal tissue during photodynamic therapy (PDT) and thus greatly enhance the therapeutic ratio. This has been demonstrated in patients undergoing PDT.

[1]  D. Kessel,et al.  Chemical, biologic and biophysical studies on 'hematoporphyrin derivative'. , 1985, Advances in experimental medicine and biology.

[2]  H. Kato,et al.  Fluorescence fiberoptic bronchoscopy in the diagnosis of early stage lung cancer. , 1982, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[3]  J. H. Kinsey,et al.  Detection and localization of In situ carcinoma of the bladder with hematoporphyrin derivative. , 1982, Mayo Clinic proceedings.

[4]  J Moan,et al.  Uptake of the components of hematoporphyrin derivative by cells and tumours. , 1983, Cancer letters.

[5]  Svaasand Lo,et al.  Optical dosimetry for direct and interstitial photoradiation therapy of malignant tumors. , 1984 .

[6]  T. Dougherty,et al.  Determination of [3H]- and [14C]hematoporphyrin derivative distribution in malignant and normal tissue. , 1979, Cancer research.

[7]  T J Dougherty,et al.  Identification of singlet oxygen as the cytotoxic agent in photoinactivation of a murine tumor. , 1976, Cancer research.

[8]  J. Moan,et al.  Porphyrin-sensitized photoinactivation of cells in vitro. , 1984, Progress in clinical and biological research.

[9]  T. Dougherty,et al.  Studies on the mechanism of tumor destruction by photoradiation therapy. , 1984, Progress in clinical and biological research.

[10]  L. O. Svaasand,et al.  Optical dosimetry for direct and interstitial photoradiation therapy of malignant tumors. , 1984, Progress in clinical and biological research.

[11]  A. M. Olsen,et al.  The use of a derivative of hematoporphyrin in tumor detection. , 1961 .

[12]  T J Dougherty,et al.  The structure of the active component of hematoporphyrin derivative. , 1984, Progress in clinical and biological research.

[13]  T. Dougherty.  Photosensitization of malignant tumors. , 1986, Seminars in surgical oncology.

[14]  T. Mang,et al.  Photofrin II levels by in vivo fluorescence photometry. , 1984, Progress in clinical and biological research.