Pharmacokinetics of the photosensitizers aminolevulinic acid and aminolevulinic acid hexylester in oro-facial tumors embedded in the chorioallantois membrane of a hen's egg.
BACKGROUND
Oral squamous-cell carcinoma is a frequent form of cancer in the head and neck region. The survival rate is poor. Therapy success is highly dependent on the stage of cancer development at which diagnosis is made. The disease is mostly diagnosed at a late stage. Photodynamic diagnosis is a new tool for screening examinations. This technique calls for reliable photosensitizers, such as aminolevulinic acid (ALA) and aminolevulinic acid hexylester (h-ALA). ALA and h-ALA are the source material for the synthesis of protoporphyrin IX in tumor cells. Protoporphyrin IX has a high detection rate for tumor tissue within a reasonable period of time.


METHODS
Tumor specimens were harvested from oral carcinomas and basaliomas of the face. The vital cells of the specimens and the human tumor cell line (CLS- 354) were cultured in a 90% RPMI and 10% fetal bovine serum medium. A constant number of 50,000 cells from each specimen and the cell line were transferred to an in vivo model on the hen's egg model. The grown specimens were tested for tumor fluorescence with ALA and h-ALA. The intensity of tumor fluorescence during the following 24 hours was measured spectroscopically as the degree of concentration of protoporphyrin IX within the cells.


RESULTS
All tumors showed higher protoporphyrin IX enrichment and fluorescence, compared to healthy tissue. Using h-ALA, the peak concentration of protoporphyrin IX was achieved 20%-25% more quickly with 3- or 6-mM solutions than with ALA. The highest contrast between tumorous and healthy tissue achieved owing to fluorescence was 1:11 using h-ALA, compared to 1:5 using ALA with the peak concentrations of protoporphyrin IX.


CONCLUSIONS
Using h-ALA, the peak concentration of protoporphyrin IX, compared to ALA, is achieved 20% percent more quickly and with twice as much contrast between tumorous and healthy tissue (1:11 compared and 1:5, respectively). This facilitates a faster, better discrimination between tumorous and healthy tissue.
Hoppenheit
Christian
C
Department of Maxillofacial Surgery, University of Saarland, Germany.
Hüttenberger
Dirk
D
Foth
Hans-Jochen
HJ
Spitzer
Wolfgang J
WJ
Reichert
Torsten E
TE
Müller-Richter
Urs D A
UD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000622:Aminolevulinic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000818:Animals; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000187:drug effects* / Q000473:pathology; D004952:Esters / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D023421:Models, Animal; D015394:Molecular Structure; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010063:Ovum / Q000166:cytology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D004952:Esters; D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid