Uptake, localization, and photodynamic effect of meso-tetra(hydroxyphenyl)porphine and its corresponding chlorin in normal and tumor tissues of mice bearing mammary carcinoma.
By using a chemical extraction assay and confocal laser scanning fluorescence microscopy, the kinetic patterns of uptake, elimination, and localization of meso-tetra(hydroxyphenyl)porphine (m-THPP) and its corresponding chlorin (m-THPC) in tumors and various normal tissues of female C3D2/F1 mice bearing CaD2 mammary carcinoma were studied after an i.p. injection of either 5 mg/kg body weight of m-THPP or 1 mg/kg body weight of m-THPC. Moreover, the histological and ultrastructural alterations of the tumors were evaluated after photodynamic therapy (PDT) with m-THPP or m-THPC. The PDT efficacy with m-THPP and m-THPC was also compared. Both m-THPP and m-THPC had a similar kinetic pattern of distribution in the tumors and most normal tissues examined. The concentrations of the dyes in the tissues peaked at 24-48 h after injection. The peak values of the uptake of m-THPP by the tissues were found to decrease in the following order: spleen > urinary tract > kidney > liver > lung > tumor > heart > skin > muscle > brain. However, higher concentrations of m-THPC were taken up by the tumors than by most of the normal tissues studied except for the liver, urinary tract, and skin. m-THPP was mainly localized in the stroma of the tumors, whereas m-THPC was distributed in both vascular interstitium and neoplastic cells of the tumors. Morphological studies showed that PDT with m-THPP resulted in destructive changes in the microvasculature of the tumors, whereas m-THPC-based PDT destroyed both vascular walls and tumor cells of the tumors. The m-THPP-PDT of the tumors was much less efficient than m-THPC-PDT of the tumors, although the dose of m-THPP used was five times higher than that of m-THPC. m-THPP and m-THPC have different efficiency of sensitizing tumors to photodestruction, although they are similar with respect to hydrophobicity. This is likely due to the differences in their intratumoral localization patterns and in their absorption spectra.
Peng
Q
Q
Department of Pathology, Norwegian Radium Hospital, Montebello, Oslo.
Moan
J
J
Ma
L W
LW
Nesland
J M
JM
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001692:Biological Transport; D005260:Female; D008027:Light; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008652:Mesoporphyrins / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000378:metabolism; D010778:Photochemotherapy; D011166:Porphyrins / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012867:Skin / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D008652:Mesoporphyrins; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; C051233:5,10,15,20-tetra(3-hydroxyphenyl)porphyrin; C072269:temoporfin