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 (PDT) for cancer patients has developed into an important new clinical treatment modality in the past 25-years. PDT involves administration of a tumor-localizing photosensitizer or photosensitizer prodrug (5-aminolevulinic acid [ALA], a precursor in the heme biosynthetic pathway) and the subsequent activation of the photosensitizer by light. Although several photosensitizers other than ALA-derived protoprophyrin IX (PpIX) have been used in clinical PDT, ALA-based PDT has been the most active area of clinical PDT research during the past 5 years. Studies have shown that a higher accumulation of ALA-derived PpIX in rapidly proliferating cells may provide a biologic rationale for clinical use of ALA-based PDT and diagnosis. However, no review updating the clinical data has appeared so far. A review of recently published data on clinical ALA-based PDT and diagnosis was conducted. Several individual studies in which patients with primary nonmelanoma cutaneous tumors received topical ALA-based PDT have reported promising results, including outstanding cosmetic results. However, the modality with present protocols does not in general, appear to be superior to conventional therapies with respect to initial complete response rates and long term recurrence rates, particularly in the treatment of nodular skin tumors. Topical ALA-PDT does have the following advantages over conventional treatments: it is noninvasive; it produces excellent cosmetic results; it is well tolerated by patients; it can be used to treat multiple superficial lesions in short treatment sessions; it can be applied to patients who refuse surgery or have pacemakers and bleeding tendency; it can be used to treat lesions in specific locations, such as the oral mucosa or the genital area; it can be used as a palliative treatment; and it can be applied repeatedly without cumulative toxicity. Topical ALA-PDT also has potential as a treatment for nonneoplastic skin diseases. Systemic administration of ALA does not seem to be severely toxic, but the advantage of using this approach for PDT of superficial lesions of internal hollow organs is still uncertain. The ALA-derived porphyrin fluorescence technique would be useful in the diagnosis of superficial lesions of internal hollow organs. Promising results of ALA-based clinical PDT and diagnosis have been obtained. The modality has advantages over conventional treatments. However, some improvements need to be made, such as optimization of parameters of ALA-based PDT and diagnosis; increased tumor selectivity of ALA-derived PpIX; better understanding of light distribution in tissue: improvement of light dosimetry procedure; and development of simpler, cheaper, and more efficient light delivery systems.Cancer 07/1997; 79(12):2282-308. · 5.20 Impact Factor
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ABSTRACT: In an ideal world, photodynamic therapy (PDT) of abnormal tissue would reliably spare the surrounding normal tissue. Normal tissue responses set the limits for light and drug dosimetry. The threshold fluence for necrosis (TFN) was measured in normal skin following intravenous infusion with a photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA) Verteporin as a function of drug dose (0.25-2.0 mg/kg), wavelength of irradiation (458 and 690 nm) and time interval (0-5 h) between drug administration and irradiation. The BPD-MA levels were measured in plasma and skin tissue to elucidate the relationship between TFN, drug kinetics and biodistribution. The PDT response of normal skin was highly reproducible. The TFN for 458 and 690 nm wavelengths was nearly identical and the estimated quantum efficiency for skin response was equal at these two wavelengths. Skin phototoxicity, quantified in terms of 1/TFN, closely correlated with the plasma pharmacokinetics rather than the tissue pharmacokinetics and was quadratically dependent on the plasma drug concentration regardless of the administered drug dose or time interval between drug and light exposure. This study strongly suggests that noninvasive measurements of the circulating drug level at the time of light treatment will be important for setting optimal light dosimetry for PDT with liposomal BPD-MA, a vascular photosensitizer.Photochemistry and Photobiology 11/1998; 68(4):575-83. · 2.29 Impact Factor
Article: The biology of photodynamic therapy.[Show abstract] [Hide abstract]
ABSTRACT: The subcellular, cellular and tissue/tumour interactions with non-toxic photosensitizing chemicals plus non-thermal visible light (photodynamic therapy (PDT) are reviewed. The extent to which endothelium/vasculature is the primary target is discussed, and the biochemical opportunities for manipulating outcome highlighted. The nature of tumour destruction by PDT lends itself to imaging outcome by MRI and PET.Physics in Medicine and Biology 06/1997; 42(5):913-35. · 2.70 Impact Factor