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.


CONCLUSIONS
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.
Hautmann
Hubert
H
Medizinische Klinik I, Klinikum rechts der Isar, Technische Universität, Munich, Germany. hautmann@web.de
Pichler
Josef P
JP
Stepp
Herbert
H
Baumgartner
Reinhold
R
Gamarra
Fernando
F
Huber
Rudolf M
RM
D000280:Administration, Inhalation; D000368:Aged; D000369:Aged, 80 and over; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology*; D001984:Bronchial Neoplasms / Q000378:metabolism* / Q000473:pathology*; D001999:Bronchoscopy / Q000379:methods*; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008856:Microscopy, Fluorescence / Q000379:methods; D008875:Middle Aged; D017319:Photosensitizing Agents / Q000008:administration & dosage; D011524:Protoporphyrins / Q000008:administration & dosage; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX