The effects of photodynamic therapy using differently substituted zinc phthalocyanines on vessel constriction, vessel leakage and tumor response.
The effects of four different zinc phthalocyanines were studied during and after photodynamic therapy (PDT). Measurements of vessel constriction, vessel leakage, tumor interstitial pressure, eicosanoid release, and tumor response of chondrosarcoma were made in Sprague-Dawley rats. Animals were injected intravenously with 1 mumol/kg of mono-, di-, or tetrasulfonated zinc phthalocyanine, or 1 mumol/kg of a zinc phthalocyanine substituted with four tertiary butyl groups. Tissues were exposed to 400 J/cm2 670 nm light 24 h after photosensitizer injection. An additional group of animals was given indomethacin before treatment. The use of the monosulfonated and tertiary butyl substituted zinc phthalocyanines in PDT caused the release of specific eicosanoids, caused vessel constriction, and induced venule leakage and increases in tumor interstitial pressure. Tumor cures of 27% and 7% were observed. Photodynamic therapy using the disulfonated zinc phthalocyanine did not induce vessel constriction or the release of eicosanoids, however, tumor cure was 43%. The use of the tetrasulfonated zinc phthalocyanine caused intermediate effects between the mono- and disulfonated compounds. The administration of indomethacin to animals completely inhibited the effects of PDT using the monosulfonated compound but had minimal effects on treatment using the disulfonated compound. This suggests that the monosulfonated and disulfonated compounds act by different mechanisms of destruction.
Fingar
V H
VH
Department of Surgery, University of Louisville, KY 40292.
Wieman
T J
TJ
Karavolos
P S
PS
Doak
K W
KW
Ouellet
R
R
van Lier
J E
JE
D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D002813:Chondrosarcoma / Q000188:drug therapy*; D015777:Eicosanoids / Q000097:blood; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use*; D007213:Indomethacin / Q000494:pharmacology; D054833:Isoindoles; D008027:Light; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009942:Organometallic Compounds / Q000494:pharmacology* / Q000627:therapeutic use*; D010778:Photochemotherapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014661:Vasoconstriction / Q000187:drug effects; D014699:Venules / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D015032:Zinc / Q000494:pharmacology / Q000627:therapeutic use; D017967:Zinc Compounds
D015777:Eicosanoids; D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine; D015032:Zinc; D007213:Indomethacin