Evaluation of porfimer sodium fluorescence for measuring tissue transformation.
BACKGROUND
Neoplastic tissue can be detected by its increased fluorescence compared with surrounding normal tissue after the injection of the tumor-localizing compound porfimer sodium (Photofrin; Quadra Logic Technologies, Vancouver, BC, Canada). In vivo fluorescence photometry is a nonimaging photodetector technique that detects specific 690 nm fluorescence of the porphyrin by subtracting nonspecific 612 nm excitation from 630 nm excitation. The technique was applied in the developmental stages of the 9,10 dimethyl-1,2-benzanthracene (DMBA)-induced hamster buccal cheek pouch carcinoma model to (1) quantitate and characterize porfimer sodium fluorescence and uptake as it relates to lesion progression and biochemical changes and (2) determine whether porfimer sodium-induced fluorescence will vary with promotional and inhibitory stimuli.


METHODS
Groups of Syrian Golden hamsters had their cheek pouch buccal mucosa exposed to a 0.5% DMBA in acetone three times per week for 6 weeks (premalignant lesions), 12 weeks (squamous cell carcinomas), or other specified durations. The rate of malignant transformation was either promoted (by either carbon dioxide laser incision or continued DMBA application) or inhibited (by the administration of either somatostatin analogue RC-160 [D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2] or bombesin antagonist RC-3095 [D-Tpi-Gln-Trp-Ala-Val-Gly-His-Leu psi (CH2NH)Leu-NH2]). Groups of DMBA-exposed hamsters were subsequently injected with 1.0 mg/kg of porfimer sodium during the various stages of tumor development. Twenty-four hours after injection, fluorescence levels were measured by in vivo fluorescence photometry. Samples of tumors, dysplastic mucosal tissue, and normal-appearing oral mucosa were biopsied and used for either tissue extraction assays, histopathologic examination, or tyrosine kinase activity assay as an index of rate of transformation.


RESULTS
Results demonstrated that porfimer sodium is retained in DMBA-treated tissue. Fluorescence is completely accounted for by porfimer sodium uptake. The duration of exposure to carcinogen is proportional to porfimer sodium fluorescence. This relationship establishes that premalignant lesions can be distinguished from normal tissue by porfimer sodium uptake and fluorescence. The changes in increased tyrosine kinase activity paralleled the increase in porfimer sodium fluorescence. Alterations in the rate of tissue transformation produced equivalent alterations in porfimer sodium-induced fluorescence.


CONCLUSIONS
These results suggest that porfimer sodium uptake and fluorescence can be used in a prognostic manner to diagnose and determine the course of transformation of individual lesions.
Crean
D H
DH
Photodynamic Therapy Center, Roswell Park Cancer Institute, Buffalo, NY 14263.
Liebow
C
C
Penetrante
R B
RB
Mang
T S
TS
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D002610:Cheek; D006224:Cricetinae; D017323:Dihematoporphyrin Ether / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D005453:Fluorescence; D008647:Mesocricetus; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology; D010783:Photometry; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology
D010446:Peptide Fragments; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; C051458:vapreotide; D013004:Somatostatin; D015127:9,10-Dimethyl-1,2-benzanthracene; D017323:Dihematoporphyrin Ether; D011505:Protein-Tyrosine Kinases; D001839:Bombesin