Uptake and kinetics of 5-aminolevulinic acid in oral squamous cell carcinoma.
Photodynamic diagnosis (PDD) is a form of cancer detection based on the administration of an exogenous photo-activated compound that accumulates in malignant cells, followed by appropriate photo irradiation. The authors describe a spectroscopic study of 5-aminolevulinic acid (5-ALA)-generated photosensitizer protoporphyrin IX (PpIX) fluorescence in human oral squamous cell carcinoma (OSCC) cell lines to validate its clinical use. 5-ALA-induced PpIX fluorescence intensity was measured in the presence and absence of deferoxamine mesylate (DFO). Two, one and two cell lines produced poorly, moderately and well differentiated carcinomas, respectively, on transplantation in scid mice. The fluorescence intensity was high in the poorly differentiated cell lines, followed by the moderately differentiated cell line; the intensity of the well differentiated cell lines was low and not significantly different from that of normal keratinocytes in the absence of DFO. It was elevated to the level of poorly differentiated cell lines following DFO treatment. This elevation was not observed in normal keratinocytes. The results indicate that DFO enhances the photodynamic sensitivity of 5-ALA in non-responsive carcinoma cells as a result of increased cellular accumulation by inhibiting haeme biosynthesis. This PDD system can be applied clinically to the detection of OSCC irrespective of the degree of differentiation.
Uekusa
M
M
Oral and Maxillofacial Surgery, Department of Oral Restitution, Division of Oral Health Sciences, Graduate School, Tokyo Medical and Dental University, Japan.
Omura
K
K
Nakajima
Y
Y
Hasegawa
S
S
Harada
H
H
Morita
K-I
KI
Tsuda
H
H
D021542:Amino Acids, Neutral / Q000493:pharmacokinetics* / Q000528:radiation effects; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D003676:Deferoxamine; D004338:Drug Combinations; D004357:Drug Synergism; D005453:Fluorescence; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D014407:Tumor Cells, Cultured
D021542:Amino Acids, Neutral; D004338:Drug Combinations; D017319:Photosensitizing Agents; D011524:Protoporphyrins; C013809:5-aminovaleric acid; C028025:protoporphyrin IX; D003676:Deferoxamine