Chloroaluminum sulfonated phthalocyanine partitioning in normal and intimal hyperplastic artery in the rat. Implications for photodynamic therapy.
Photodynamic therapy, the light activation of photosensitizers into cytotoxic mediators, has been a successful treatment for experimental intimal hyperplasia (IH). To understand the basis of the photosensitizer chloroaluminum sulfonated phthalocyanine (CASPc)-mediated photoinhibition of intimal hyperplasia in the rat common carotid artery model, we studied photosensitizer partitioning in hyperplastic as compared to normal arterial tissue. Serum clearance of CASPc is exponential with, a half-life of 300 minutes. Laser-induced fluorescence and spectrofluorimetric analyses of artery tissue demonstrated an approximately 60% lower uptake and retention of CASPc by normal arterial tissue as compared to arteries with IH; the differences become more pronounced at 24 h. Fluorescent microscopy of arterial tissue demonstrated increased uptake of the CASPc by the artery with IH. However, by 24 h it is primarily the IH tissue that has retained the CASPc, with clearance of the dye from the media of normal or hyperplastic arteries. These data demonstrate that IH, like neoplastic tissue, has an increased accumulation of CASPc compared to normal artery. The preferential partitioning into hyperplastic tissue has implications for therapeutic targeting of this cellular population with photodynamic therapy.
LaMuraglia
G M
GM
Vascular Surgery Division of the General Surgical Services, Massachusetts General Hospital, Boston 02114.
Ortu
P
P
Flotte
T J
TJ
Roberts
W G
WG
Schomacker
K T
KT
ChandraSekar
N R
NR
Hasan
T
T
D000818:Animals; D001158:Arteries / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology*; D017536:Carotid Artery, Common / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000032:analysis / Q000235:genetics; D006207:Half-Life; D006965:Hyperplasia / Q000532:radiotherapy; D007211:Indoles / Q000032:analysis* / Q000097:blood; D007834:Lasers; D008297:Male; D008856:Microscopy, Fluorescence; D009942:Organometallic Compounds / Q000032:analysis* / Q000097:blood; D010789:Phototherapy; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000737:chemistry / Q000378:metabolism / Q000473:pathology
D007211:Indoles; D009942:Organometallic Compounds; D011838:Radiation-Sensitizing Agents; C052736:chloroaluminum tetrasulfophthalocyanine; D004247:DNA