In vitro and in vivo uptake of benzoporphyrin derivative into human and miniswine atherosclerotic plaque.
Benzoporphyrin derivative (BPD) has been demonstrated to be a new potent photosensitizer for photodynamic therapy (PDT). Although most of the work on BPD has been focused on its potential applications for cancer treatment, BPD may have potential clinical uses in the treatment of atherosclerosis. The purpose of this study was to determine in vitro and in vivo uptake of BPD into atherosclerotic plaque. Samples of atherosclerotic human femoral and popliteal arteries were incubated with BPD-monoacid, ring A (BPD-MA) for 1 h in the following concentrations: 1, 5, 10, 20, 30 and 40 micrograms/mL. Fluorescence from all samples was determined by chemical extraction with a spectrofluorometer. The tissue concentration for human arteries was 0.37 +/- 0.03, 2.78 +/- 1.5, 3.6 +/- 1.91, 7.15 +/- 2.36, 8.06 +/- 3.09 and 14.6 +/- 4.81 micrograms/g, respectively. In addition, three miniswine were rendered atherosclerotic and given BPD 2.0 mg/kg intravenously. The concentration of BPD-MA in miniswine aorta was 93-190 ng/g and the plaque/normal ratio was 1.7-3.5. For miniswine iliac arteries, the [BPD-MA] was 60-178 ng/g and the plaque/normal ratio was 1.1-3.3. Normal miniswine carotid artery contained 54 ng/g. This study showed that BPD-MA was taken up in atherosclerotic vessels both in vitro and in vivo and may have potential for PDT of atherosclerosis.
Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Y N
YN
Hsiang
M T
MT
Crespo
A M
AM
Richter
A K
AK
Jain
M
M
Fragoso
J G
JG
Levy
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D001692:Biological Transport; D005260:Female; D005263:Femoral Artery / Q000378:metabolism; D006801:Humans; D007083:Iliac Artery / Q000378:metabolism; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D017319:Photosensitizing Agents / Q000378:metabolism* / Q000493:pharmacokinetics; D011150:Popliteal Artery / Q000378:metabolism; D011166:Porphyrins / Q000378:metabolism* / Q000493:pharmacokinetics; D013552:Swine; D013556:Swine, Miniature
D017319:Photosensitizing Agents; D011166:Porphyrins; C504224:benzoporphyrin D