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
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.