Pharmacokinetics of fluorescent polyporphyrin Photofrin II in normal rat tissue and rat bladder tumor.
ABSTRACT The transient behavior of the molecular components responsible for fluorescence emission of the photosensitizing polyporphyrin Photofrin II has been studied quantitatively in the liver, small intestines, bladder and muscles of rats. Relative concentrations of the substance were determined fluorometrically in vivo using a Kr(+)-laser (wavelength = 406.7 nm) and a mercury arc lamp (wavelength = 405 or 550 nm) for fluorescence excitation of Photofrin II. Fluorescence was detected at the maxima of the emission bands, at 630 or 690 nm. The results of the experiments show that Photofrin II can be clearly detected by its fluorescence in all the organs investigated from 3 h up to at least 28 days after systemic application of the substance. Within this investigational period the fluorescing components of Photofrin II are released continuously from the organs. In all the tissues examined, an initial decrease with time constants between 2 and 42 h followed by a slow decay with time constants between about 300 and 600 h can be observed. In addition the pharmacokinetics of the fluorescent components of Photofrin II in chemically induced rat bladder tumors with different stages of malignancy were compared to healthy rat bladder tissue. In a time range of 2-10 days after intravenous injection Photofrin II shows a fluorescence 2-5 times brighter in rat bladder tumors than in healthy bladder tissue.
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ABSTRACT: Photodynamic therapy is a new, experimental method of treating malignant tumors by utilizing the relatively selective retention of the photosen-sitizer (hematoporphyrin derivative or dihematoporphyrin ether) and its ability to elicit an efficient photodynamic reaction upon activation with penetrating viable light. Application of this therapy to tumors in the bronchus, bladder, skin, and several other sites has demonstrated both safety and efficacy, even in advanced cases. Eradication of early stage tumors in the bronchus and bladder has been demonstrated. Selective retention of the photosensitizers in tumors is apparently related to the relatively large size of the aggregates of these materials causing phagocytosis by reticuloendothelial cells as well as preventing rapid clearance from tumor interstitial fluid and subsequent uptake in lipophylic components of cells. Upon light activation, generally delivered from lasers via fiber optics, the sensitizers generate singlet oxygen, the apparent cytotoxic agent, causing both vascular damage and injury to tumor cells.Seminars in Surgical Oncology 12/1985; 2(1):24 - 37.
- Photochemistry and Photobiology 12/1987; 46(5):759-63. · 2.29 Impact Factor
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ABSTRACT: Laser-induced fluorescence in rat tissue was studied during the uptake and clearing period of i.v.-injected hematoporphyrin derivative. A malignant rat tumor and normal tissue of 20 different kinds from the tumor-bearing animals were investigated. A pulsed nitrogen laser (337 nm) was used in conjunction with an optical multichannel analyzer system, in which the whole fluorescence light distribution was captured for each laser pulse. Several of the organs exhibited an initial and a delayed intensity peak in the characteristic hematoporphyrin derivative laser-induced fluorescence intensity (630 nm) that might be interpreted as due to intracellular transformations of different chemical components of the hematoporphyrin derivative preparation. By dividing the background-free 630-nm signal by the blue fluorescence intensity, a dimensionless quantity is obtained that could have many advantages in practical endoscopic laser-induced fluorescence work. This ratio was also shown to exhibit a larger contrast between tumor and surrounding tissue. The ratio between the two red fluorescence peaks was also found to be useful for discriminating tumor from normal tissue. A combination of the two ratios was shown to be particularly valuable for tumor discrimination.Cancer Research 09/1986; 46(8):3803-8. · 8.65 Impact Factor