R. Baumgartner et al., INHALATION OF 5-AMINOLEVULINIC ACID - A NEW TECHNIQUE FOR FLUORESCENCE DETECTION OF EARLY-STAGE LUNG-CANCER, Journal of photochemistry and photobiology.B, Biology, 36(2), 1996, pp. 169-174
Topical application of 5-aminolevulinic acid (5-ALA), with subsequent
synthesis of protoporphyrin IX (PPIX),is a novel outstanding procedure
for photodynamic treatment. So far, clinical experience has been repo
rted with creams containing 5-ALA for the therapy of skin cancer, oral
application for the treatment of gastrointestinal disease and intrave
sical instillation of 5-ALA solutions for fluorescence detection of su
perficial bladder cancer. Inhalation of 5-ALA for the staining of bron
chial malignancies is a preferred method in clinical pulmonology. Sinc
e no adverse reaction was observed in lung function in a canine follow
ing inhalation of 5-ALA in increasing concentrations, clinical applica
tions were performed. Seven patients with positive or suspicious sputu
m cytology, but negative white light bronchoscopy, received 5-10 wt.%
5-ALA in NaCl solution by means of a medical nebulizer. No side effect
s were observed during and after 5-ALA inhalation. After a period of 3
h, patients underwent fluorescence bronchoscopy using violet light fo
r fluorescence excitation and an optical multichannel analyzer for flu
orescence detection in situ. The results showed fluorescence spectra w
hich could be related to PPIX induced by 5-ALA in the bronchial mucosa
. The fluorescence intensity was sufficiently high for video imaging u
sing a target integrating color CCD camera adapted to the flexible bro
nchoscope. Carcinoma in situ, as well as dysplasias, showed a clear po
sitive fluorescence. A correlation of fluorescence contrast with histo
logy on 30 biopsies revealed a high sensitivity, but a specificity bel
ow 50%. Improvements in light and drug dosimetry will form the basis f
or further clinical trials.