In-vivo kinetics of inhaled 5-aminolevulinic acid-induced protoporphyrin IX fluorescence in bronchial tissue

Background: In the diagnosis of early-stage lung cancer
photosensitizer-enhanced fluorescence bronchoscopy with inhaled
5-aminolevolinic acid ( 5-ALA) increases sensitivity when compared
to white-light bronchoscopy. This investigation was to evaluate the
in vivo tissue pharmacokinetics of inhaled 5-ALA within the
bronchial mucosa in order to define the time optimum for its
application prior to bronchoscopy. Methods: Patients with known or
suspected bronchial carcinoma were randomized to receive 200 mg
5-ALA via inhalation 1, 2, 3, 4 or 6 hours before flexible
fluorescence bronchoscopy was performed. Macroscopically suspicious
areas as well as areas with visually detected porphyrin
fluorescence and normal control sites were measured
spectroscopically. Biopsies for histopathology were obtained from
suspicious areas as well as from adjacent normal areas. Results:
Fluorescence bronchoscopy performed in 19 patients reveals a
sensitivity for malignant and premalignant changes ( moderate
dysplasia) which is almost twice as high as that of white-light
bronchoscopy, whereas specificity is reduced. This is due to
false-positive inflammatory lesions which also frequently show
increased porphyrin fluorescence. Malignant and premalignant
alterations produced fluorescence values that are up to 5 times
higher than those of normal tissue. According to the
pharmacokinetics of porphyrin fluorescence measured by
spectroscopy, the optimum time range for 5-ALA application is
80-270 min prior to fluorescence bronchoscopy, with an optimum at
160 min. Conclusion: According to our results we propose inhalation
of 5-ALA 160 min prior to fluorescence bronchoscopy, suggesting
that this time difference provides the best tumor/normal tissue
fluorescence ratio.