Photosensitization of experimental hepatocellular carcinoma with protoporphyrin synthesized from administered delta-aminolevulinic acid: studies with cultured cells and implanted tumors.
OBJECTIVE
Photodynamic therapy using porphyrins or related compounds and laser light is an investigational treatment for neoplasms. The aim of this study was to establish whether this might be applicable for hepatocellular carcinoma using protoporphyrin synthesized in the tissue from administered delta-aminolevulinic acid.


METHODS
We measured porphyrin accumulation in normal rat hepatocytes and Morris hepatoma cells in culture, and in subcutaneously implanted hepatomas and other tissues of the rat after administration of delta-aminolevulinic acid, and assessed cell and tissue damage after application of laser light.


RESULTS
Porphyrin accumulation after delta-aminolevulinic acid was added to the medium was greater and continued to increase for a longer period of time in hepatoma cells than in hepatocytes (1337+/-42 vs 513+/-31 fluorescence units/cell at 8 h, means+/-SE, p<0.001). After intraperitoneal injection of delta-aminolevulinic acid to rats with subcutaneously growing hepatomas, porphyrin content in tumor and liver was similar at 4 h but was higher in tumor at 6 h. Laser light caused necrosis of normal and malignant liver cells in culture and subcutaneous hepatomas in vivo.


CONCLUSIONS
We conclude from these in vitro and in vivo studies that porphyrin accumulation after administration of delta-aminolevulinic acid in this hepatoma is substantial and time dependent, and delivery of laser light locally can cause tumor photosensitization and necrosis.
Egger
N G
NG
Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston 77555-1109, USA.
Schoenecker
J A
JA
Gourley
W K
WK
Motamedi
M
M
Anderson
K E
KE
Weinman
S A
SA
D000622:Aminolevulinic Acid / Q000627:therapeutic use*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D066298:In Vitro Techniques; D053685:Laser Therapy; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009336:Necrosis; D009368:Neoplasm Transplantation; D010778:Photochemotherapy; D010782:Photolysis; D017319:Photosensitizing Agents / Q000378:metabolism* / Q000627:therapeutic use*; D011524:Protoporphyrins / Q000096:biosynthesis* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid