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 intraveneous injection Photofrin II shows a fluorescence 2–5 times brighter in rat bladder tumors than in healthy bladder tissue.
[Show abstract][Hide abstract] ABSTRACT: The bladders of anaesthetised mice were illuminated with red laser light (630 nm) at intervals of 1 day to 4 weeks after i.p. administration of Photofrin. Light was delivered intravesically by inserting a fibre optic, with a diffusing bulb tip, into the centre of fluid filled bladders. A single light dose of 11.3 J cm-2 applies 1 day after 10 mg kg-1 Photofrin caused a severe acute response, with increased urination frequency (five to seven times control) and hematuria. Recovery was good, however, and by 10 weeks only a mild (approximately two-fold) increase in frequency remained. There was no reduction in the amount of acute bladder damage or in the rate of healing when the interval between Photofrin and light was increased from 1 to 7 days but a 2 to 3 week interval lead to a significant reduction in damage. For an interval of 4 weeks there was only a mild (less than two-fold) increase in urination frequency during the first week. A drug dose of 2.5 mg kg-1 given 1 day before illumination caused transient haematuria but no increase in urination frequency. Doses of 5, 7.5 or 10 mg kg-1 all caused photosensitisation and the amount of bladder damage was drug dose dependent. The bladder seems to be well able to recover from severe acute damage induced by PDT. Occasional incidences of pyelonephritis were seen, however, suggesting that urinary tract infection during the acute period may lead to permanent renal damage.
British Journal of Cancer 11/1993; 68(4):673-7. DOI:10.1038/bjc.1993.407 · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cellular fluorescence intensity (CFI) after incubation with varying concentrations of the photosensitizer Photofrin and the
photodynamically induced dose-response relationships of hamster melanoma cells (A-MEL-3) were studied in a recently developed
in vitro model. After administration of Photofrin to the extracellular serum-free medium, CFI was evaluated by flow cytometry
together with constantly fluorescing latex particles used as a reference. After 5 min, 50% of maximal CFI was found, and after
60 min CFI was maximal. No further increase was obtained during the exposure to Photofrin over the incubation period of 4
h. During this plateau phase, CFI was significantly related to the concentration of Photofrin in the extracellular medium
(r=0.94;P<0.001). Subsequent to increasing intervals of Photofrin exposure, cells were irradiated with laser light at 630 nm (40 mW/cm2, 4J). Cell viability as evaluated by trypan blue exclusion was significantly decreased with increasing concentrations of
Photofrin in the medium, and significantly correlated with CFI during the plateau phase. After photodynamic treatment (PDT)
cell fluorescence was reduced by about 15%. This was neither dose- nor time-dependent. On the basis of these findings we propose
that CFI indicates photosensitizer uptake. This is also supported by the relation between CFI and phototoxicity. The latter
also suggests that CFI might be useful to predict the PDT in vivo efficacy by this in vitro model. Besides measurements of
photosensitizer uptake and cell photoxicity, the model demonstrates and excellent opportunity to study the molecular mechanisms
of action associated with PDT.
Research in Experimental Medicine 11/1993; 193(1):361-370. DOI:10.1007/BF02576244
[Show abstract][Hide abstract] ABSTRACT: Laser-induced fluorescence has been used to measure tissue levels of chloroaluminum sulfonated phthalocyanine in vivo in an implanted hamster cheek pouch carcinoma tumor model. The drug was excited at 610 nm via a pulsed nitrogen laser-pumped dye laser, and fluorescence intensity was monitored at 684 nm for up to 30 days after drug administration. Data were acquired noninvasively with high temporal and spatial resolution using the laser-induced fluorescence apparatus and were analyzed with a multicompartment pharmacokinetic model. In addition, our published data on a C6-BAG glioma rat brain tumor model were analyzed to illustrate the effect of different tumor models on the rates. The rates extracted from the pharmacokinetic model elucidate the mechanisms of drug uptake and retention in the cheek pouch and brain tumor models. The laser-induced fluorescence approach should lead to better drug dosimetry for photochemotherapy and allow quick characterization of the pharmacokinetics of new photosensitizers in tissue.
Cancer Research 01/1994; 53(24):5954-61. · 9.33 Impact Factor
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