ORAL VERSUS INTRAVENOUS ADMINISTRATION OF 5-AMINOLEVULINIC ACID FOR PHOTODYNAMIC THERAPY

Citation
Cs. Loh et al., ORAL VERSUS INTRAVENOUS ADMINISTRATION OF 5-AMINOLEVULINIC ACID FOR PHOTODYNAMIC THERAPY, British Journal of Cancer, 68(1), 1993, pp. 41-51
Citations number
30
Categorie Soggetti
Oncology
Journal title
ISSN journal
00070920
Volume
68
Issue
1
Year of publication
1993
Pages
41 - 51
Database
ISI
SICI code
0007-0920(1993)68:1<41:OVIAO5>2.0.ZU;2-V
Abstract
Endogenously synthesised protoporphyrin IX (PpIX) following the admini stration of 5-amino-laevulinic acid (ALA) is an effective photosensiti ser for photodynamic therapy (PDT). Following intravenous administrati on, PpIX accumulates predominantly in mucosa of hollow viscera and on light exposure, mucosal ablation results with relative sparing of the submucosa and muscularis layers. Oral administration is effective with ALA in contrast to conventional exogenous photosensitisers such as ha ematoporphyrin derivative and phthalocyanines. Oral administration of ALA is also simpler, safer, cheaper and more acceptable to patients. W e studied the porphyrin sensitisation kinetics profile in the stomach, colon and bladder in normal rats following enterally and parenterally administered ALA using microscopic fluorescence photometric studies o f frozen tissue sections. Mucosal cells in all three organs exhibit hi gher fluorescence levels as compared with underlying smooth muscle fol lowing both intravenous and oral administration. Peak concentration we re seen 4 h after sensitisation at the highest doses used (200 mg kg-1 i.v., 400 mg kg-1 oral), and slightly earlier with lower doses. The t emporal kinetics of both routes of administration were similar althoug h a higher oral dose was required to achieve the same tissue concentra tion of PpIX. The highest level of fluorescence was achieved in the ga stric mucosa and in decreasing levels, colonic and bladder mucosa. A s imilar degree of mucosal selectivity was achieved in each organ with e ach route of administration but an oral dose in excess of 40 mg kg-1 w as required to achieve measurable PpIX sensitisation. In a pilot clini cal study, two patients with inoperable rectal adenocarcinomas were gi ven 30 mg kg-1 and one patient with sigmoid colon carcinoma was given 60 mg kg-1 ALA orally. Serial biopsies of normal and tumour areas were taken over the subsequent 24 h. Fluorescence microscopy of these spec imens showed maximum accumulation of PpIX 4 to 6 h after administratio n of 30 mg kg-1 ALA. There was greater PpIX accumulation in tumour tha n adjacent normal mucosa in two patients. Preferential PpIX accumulati on in tumour was greater in the patient receiving 60 mg kg-1 ALA.