[Selective hematoporphyrin derivative (HMD) application in arterial vessels using a porous balloon catheter results in equivalent levels as compared to high-dose systemic administration].
The treatment of atherosclerotic vascular stenosis with percutaneous angioplasty is limited by a rate of restenosis of about 20-40%, in spite of new angioplasty devices. Histological and immune histological examinations of restenosed material obtained by coronary atherectomy indicate that cellular proliferation is an important determinant of restenosis. With the use of photodynamic therapy (PDT), it might be possible to selectively impair proliferating tissue by the application of the photosensitizer Photofrin II (a hematoporphyrin-derivative, HPD) followed by localized laser-light radiation. With the knowledge of the success of PDT in tumor therapy, the extension of the application of PDT in prophylaxis of restenosis should be examined. The technique used up to now works with the systemic application of the sensitizer. By applying HPD locally, however, one might be able to reduce the amount of the photosensitizer, but still achieve an equally cytotoxic effect. A recently developed catheter with a porous balloon enables local application of HPD. The following study describes the uptake and distribution of the hematoporphyrin-derivative Photofrin II within the walls of elastic and muscular type vessels after systemic and selective application. In 20 rabbits and seven pigs, Photofrin II was applied systemically (5 mg/kg i.v.) and locally (5 ml of 2.5 mg/ml). From each animal 12 vascular specimens (six arterial segments of either muscular and elastic type) were removed at a definite time within a defined period of 5 min to 24 h after application. To quantify the uptake of Photofrin II, we used fluorescence microscopy with digital image processing. After systemic application there was an increase of Photofrin II over a 4-h period. In contrast, a maximum concentration of Photofrin II was measured immediately after local application and found to be decreasing over a period of 4 h. The intima showed the highest uptake of HPD, both after local and systemic applications, as compared to uptake by the media and adventitia. The intimal uptake was significantly higher after local than after systemic application. Media and the adventitia showed, respectively, only one-half and one-fifth of the intima's intake. The rapid increase of the HPD concentration after local application would make PDT feasible in restenosis prophylaxis immediately after angioplasty without systemic side-effects of the photosensitizer.
Gonschior
P
P
Medizinische Klinik I, Ludwig-Maximilians-Universität, München.
Erdemci
A
A
Gerheuser
F
F
Gonschior
G M
GM
Mack
B
B
Kolbe
T
T
Goetz
A E
AE
Höfling
B
B
D000287:Administration, Topical; D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D001158:Arteries / Q000378:metabolism; D001161:Arteriosclerosis / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D002404:Catheterization; D005260:Female; D017324:Hematoporphyrin Derivative; D006414:Hematoporphyrin Photoradiation / Q000379:methods*; D006415:Hematoporphyrins / Q000008:administration & dosage* / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D008856:Microscopy, Fluorescence; D011817:Rabbits; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D012008:Recurrence; D013552:Swine
D006415:Hematoporphyrins; D011838:Radiation-Sensitizing Agents; D017324:Hematoporphyrin Derivative
Selektive Hämatoporphyrinderivat-(HPD-)Applikation im arteriellen Gefässsystem mittels eines porösen Ballonkatheters erreicht vergleichbare Konzentrationen wie nach hochdosierter systemischer Gabe.