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Liver cancer is an aggressively malignant tumor refractory to known therapy. This study investigated the potential of hematoporphyrin (HP) and light energy to selectively photo-necrose experimental hepatoma in rats. Hepatoma cells (106) when inoculated directly into the liver of recipient Wistar rats developed into a rapidly growing neoplasm which simulated human liver cancer. Seventy-two hours following intravenous HP (5-25 mg/kg), the tumor exhibited patchy porphyrin fluorescence on gross examination and on U.V. microscopy. Fluorescence was maximal in areas furthest from blood vessels, and was within cells which morphologically appeared least viable. Liver tissue did not fluoresce but contained HP concentrations 60% of that in fluorescent tumor and 3 times greater than that in non-fluorescent viable tumor. Tumor necrosis produced by light (Tungsten, 600-640 nm, 200 mW/ sq cm, 240 joules) and HP appeared macroscopically complete to a depth of 1.5 cm. Histologically, in necrotic areas, there were islands of surviving tumor enveloping blood vessels. Three weeks after irradiation, tumor volume averaged 2 mm3 compared to 250 mm3 in control operated animals where HP containing neoplasm was exposed to diffuse room light only. Neighboring liver tissue also was necrosed reflecting HP uptake. As the liver behaved in vivo as a tumor, this provided an ideal solid tissue model to study the biology of the photodynamic action of porphyrins. The clearly visible line of demarcation between photonecrosed and living tissue allowed measurement of the depth of necrosis with an accuracy of a fraction of a millimeter. We observed the following: 1) blue light (Xenon, bandwidth 60 nm, 30 mW/sq cm, 360 joules) produced 1/10 depth of necrosis when compared to red light of the same bandwidth and energy. This may relate in part to demonstrated preferential absorption of shorter wavelength (<590 nm) light energy by liver tissue pigments and hemoglobin. 2) The depth of necrosis related to the log of incident light energy (joules/sq cm). 3) The photodynamic effect of red coherent light (545-625 nm) from a tunable dye pulse laser system was no different from that of red light from a continuous noncoherent (Tungsten) source. 4) There was a logarithmic relationship between the dose of HP administered and the depth of liver necrosis. 5) If one interposed a photoopaque shield between the incident laser light and the liver, a considerable back scattering of light caused tissue necrosis behind the shield. However, when the diameter of the shield was greater than 1.3 mm, there always was a surviving island of tissue which escaped destruction. 6) The depth of necrosis in liver (mms) was significantly less than adjacent non-pigment tumor (cms) which suggests that the optical density of the tissue is a major factor in determining effective light penetration. We conclude that measurement of tissue porphyrin, and optical density with reference to the liver, will allow precise calculation potentially of major clinical importance in the treatment of skin and mucosal cancers.
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