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To investigate pharmacokinetics of ALA-induced porphyrins the time course of fluorescence in neoplastic tissue and normal tissue following i.v. administration of ALA (100 mg kg-1, 500 mg kg-1 or 1000 mg kg-1 b.w.) was studied by means of intravital fluorescence microscopy. As a model the amelanotic melanoma (A-Mel- 3) growing in a transparent skin fold chamber preparation was used (n equals 18). Maximal fluorescence intensity was measured after 2.5 h in tumor and after 6 h in surrounding host tissue, highest tumor/host tissue ratio at 90 min (500 mg kg-1 b.w.). Heterogeneity of fluorescence intensity between different tumors ranged from 24% to 361% following injection of 500 mg/kg b.w. Twenty-four hours after systemic administration of ALA fluorescence intensity was decreased to baseline. Based upon these results a three- compartment model was calculated to simulate fluorescence kinetics in solid, well vascularized tumors assuming first-order kinetics. This compartment model supports the experimental findings, that the transient selectivity of ALA-induced fluorescence in tumors is caused by earlier uptake of ALA in tumors due to increased microvascular permeability and diffusion in neoplastic tissue. The heterogeneity might represent the different metabolic capacity of tumors to form porphyrins following exogenous administration of ALA.
Christoph Abels,Peter Heil,Marc Dellian,Gerhard E.H. Kuhnle,Reinhold Baumgartner, andAlwin E. Goetz
"Increased vascular permeability of solid tumors causes selectivity of 5-aminolevulinic acid (ALA) induced porphyrins", Proc. SPIE 2371, 5th International Photodynamic Association Biennial Meeting, (1 March 1995); https://doi.org/10.1117/12.203451
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Christoph Abels, Peter Heil, Marc Dellian, Gerhard E.H. Kuhnle, Reinhold Baumgartner, Alwin E. Goetz, "Increased vascular permeability of solid tumors causes selectivity of 5-aminolevulinic acid (ALA) induced porphyrins," Proc. SPIE 2371, 5th International Photodynamic Association Biennial Meeting, (1 March 1995); https://doi.org/10.1117/12.203451