Significance of dosimetry in photodynamic therapy of injured arteries: classification of biological responses.
With conflicting results in the literature on the ability of photodynamic therapy (PDT) to inhibit intimal hyperplasia (IH), the present study systematically investigated the effects of drug and light dosimetry on the biologic responses in the artery wall. The rat common carotid artery was balloon-injured and pressurized with benzoporphyrin-derivative monoacid ring (BPD). Then, PDT was performed with an external laser at different fluences and the biologic responses of the artery wall were histologically examined at 24 h and at 2 weeks. Photodynamic therapy effects on injured arteries can be classified into four stages: low-dose PDT using 0.5 microgram/mL BPD at 50 J/cm2 (stage I) resulted in incomplete cell eradication and significant IH at 2 weeks. Irradiation with 100 J/cm2 at the same BPD concentration (stage II) completely eradicated the cells in the artery wall at 24 h but still led to IH at 2 weeks. However, 25 micrograms/mL BPD at 100 J/cm2 (stage III) resulted in total cell eradication at 24 h and inhibition of IH at 2 weeks. In contrast, high-dose PDT with 25 micrograms/mL BPD and 200 J/cm2 (stage IV) led to thrombus development and vascular occlusion at 24 h. These data, demonstrating the different stages of PDT effects on injured arteries, emphasize the critical importance of appropriate PDT dosimetry for the effective inhibition of IH.
Adili
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F
Division of Vascular Surgery, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Statius van Eps
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RG
LaMuraglia
G M
GM
D000818:Animals; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006965:Hyperplasia; D008297:Male; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage; D011166:Porphyrins / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley
D017319:Photosensitizing Agents; D011166:Porphyrins; D016222:Fibroblast Growth Factor 2; C504224:benzoporphyrin D