Porphyrins preferentially accumulate in a melanoma following intravenous injection of 5-aminolevulinic acid

被引:30
作者
Fritsch, C
Abels, C
Goetz, AE
Stahl, W
Bolsen, K
Ruzicka, T
Goerz, G
Sies, H
机构
[1] UNIV DUSSELDORF, INST DERMATOL, D-40001 DUSSELDORF, GERMANY
[2] UNIV MUNICH, INST CHIRURG FORSCH, D-81366 MUNICH, GERMANY
[3] UNIV MUNICH, INST ANASTHESIOL, D-81366 MUNICH, GERMANY
关键词
5-aminolevulinic acid; coproporphyrin; hamster; melanoma; photodynamic therapy; porphyrin metabolism;
D O I
10.1515/bchm.1997.378.1.51
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Systemically, as opposed to topically, administered 5-aminolevulinic acid (ALA) is of increasing interest for photodynamic therapy (PDT) because of more selective and more homogeneous accumulation of porphyrins in neoplastic tissues, This study investigates the profile and the time course of porphyrin metabolites in various tissues following intravenous injection of ALA (0.5 g/kg body weight) into hamsters bearing an amelanotic melanoma (A-Mel-3). ALA injection led to maximum levels of ALA and porphyrins in erythrocytes after 45 min. In tissues, maximum porphyrin levels were detected after 45 min (tumor), 4 h (skin, kidney), and 24 h (liver). Sixfold higher porphyrin levels were observed in tumors as compared to surrounding normal skin at 45 min. Predominant porphyrin metabolites were protoporphyrin (tumor, skin, liver, kidney), coproporphyrin (tumor) and highly carboxylated porphyrins (tumor, skin, kidney). These data suggest optimum efficacy of light irradiation in systemic PDT with ALA within the first two hours after injection, Tumor-specific ALA metabolism yields protoporphyrin and coproporphyrin as the prevailing porphyrin metabolites.
引用
收藏
页码:51 / 57
页数:7
相关论文
共 32 条
[1]   IN-VIVO KINETICS AND SPECTRA OF 5-AMINOLEVULINIC ACID-INDUCED FLUORESCENCE IN AN AMELANOTIC MELANOMA OF THE HAMSTER [J].
ABELS, C ;
HEIL, P ;
DELLIAN, M ;
KUHNLE, GEH ;
BAUMGARTNER, R ;
GOETZ, AE .
BRITISH JOURNAL OF CANCER, 1994, 70 (05) :826-833
[2]  
ABELS C, 1995, ARCH DERMATOL RES, V287, P355
[3]  
BERR F, 1993, J LIPID RES, V34, P1275
[4]   STUDY OF FACTORS CAUSING EXCESS PROTOPORPHYRIN ACCUMULATION IN CULTURED SKIN FIBROBLASTS FROM PATIENTS WITH PROTOPORPHYRIA [J].
BLOOMER, JR ;
BRENNER, DA ;
MAHONEY, MJ .
JOURNAL OF CLINICAL INVESTIGATION, 1977, 60 (06) :1354-1361
[5]   EFFECTS OF DELTA-AMINOLEVULINIC-ACID ADMINISTRATION ON SOCIAL-BEHAVIOR IN THE LABORATORY MOUSE [J].
CUTLER, MG ;
MOORE, MR ;
EWART, FG .
PSYCHOPHARMACOLOGY, 1979, 61 (02) :131-135
[6]   HIGH-ENERGY SHOCK-WAVES ENHANCE HYPERTHERMIC RESPONSE OF TUMORS - EFFECTS ON BLOOD-FLOW, ENERGY-METABOLISM, AND TUMOR-GROWTH [J].
DELLIAN, M ;
WALENTA, S ;
GAMARRA, F ;
KUHNLE, GEH ;
MUELLERKLIESER, W ;
GOETZ, AE .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1994, 86 (04) :287-293
[7]   The prooxidant effect of 5-aminolevulinic acid in the brain tissue of rats: Implications in neuropsychiatric manifestations in porphyrias [J].
Demasi, R ;
Penatti, CAA ;
DeLucia, R ;
Bechara, EJH .
FREE RADICAL BIOLOGY AND MEDICINE, 1996, 20 (03) :291-299
[8]  
DOSS M, 1973, ENZYME, V16, P343
[9]   TECHNICAL REPORT - A NEW CHAMBER TECHNIQUE FOR MICRO-VASCULAR STUDIES IN UNANESTHETIZED HAMSTERS [J].
ENDRICH, B ;
ASAISHI, K ;
GOTZ, A ;
MESSMER, K .
RESEARCH IN EXPERIMENTAL MEDICINE, 1980, 177 (02) :125-134
[10]  
FORTNER JG, 1961, CANCER RES, V21, P161