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Proceedings Paper

Pharmacokinetics and efficacy of 5-aminolaevulinic acid for endovascular photodynamic therapy in a swine model
Author(s): Michael P. Jenkins; Giovanni A. Buonaccorsi; Alexander J. MacRobert; Christopher C. R. Bishop; Stephen G. Bown; Jean R. McEwan
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Paper Abstract

Vascular smooth muscle cells (VSMC) are known to be important in restenosis and photodynamic therapy (PDT) has been shown experimentally to deplete the VSMC population in small animal studies. We aimed to investigate the pharmacokinetics of 5- aminolaevulinic acid (5-ALA) and to see if endovascular PDT was feasible in a large animal model. Large White pigs (15 - 20 Kg) were photosensitized with 5-ALA at a concentration of 60 and 120 mg/Kg. Arterial biopsies were taken at intervals between 30 mins and 24 hours and snap frozen in liquid nitrogen. Frozen sections were analyzed using a CCD camera and PpIX activity assessed by computing pixel counts for intima, media and adventitia at each time point. Based on the above results 8 pigs were treated with PDT at 1.5, 2.5 or 6 hours following 5-ALA administration. Iliac segments were then illuminated with 50 J/cm2, 635 nm wavelength light via a 4 mm transparent PTA balloon. Animals were culled at 3 days and the above segments pressure perfused in situ with 4% formyl saline, before being excised and fixed. Fluorescence peaked in the adventitia at 1.5 hours, was minimal at 2.5 hours and peaked in the media at 6 hours post 5-ALA. Of the second series of 8 pigs, all animals survived to culling and all treated arteries remained patent. Histological sections stained with H&E were examined and medial VSMC's counted in 4 individual high power fields per section. The mean VSMC count per HPF for PDT treated segments was 16, 51 and 12 at 1.5, 2.5 and 6 hours respectively. VSMC counts in ALA alone controls and light alone controls were 115 and 103 respectively (p less than 0.0001). Endovascular delivery of light to 5-ALA sensitized animals is therefore feasible and was not associated with any complications.

Paper Details

Date Published: 1 July 1998
PDF: 8 pages
Proc. SPIE 3245, Lasers in Surgery: Advanced Characterization, Therapeutics, and Systems VIII, (1 July 1998); doi: 10.1117/12.312296
Show Author Affiliations
Michael P. Jenkins, Univ. College London (United Kingdom)
Giovanni A. Buonaccorsi, National Medical Laser Ctr./Univ. College London (United Kingdom)
Alexander J. MacRobert, National Medical Laser Ctr./Univ. College London (United Kingdom)
Christopher C. R. Bishop, Univ. College London (United Kingdom)
Stephen G. Bown, National Medical Laser Ctr./Univ. College London (United Kingdom)
Jean R. McEwan, The Hatter Institute and Ctr. for Cardiology/Univ. College London (United Kingdom)


Published in SPIE Proceedings Vol. 3245:
Lasers in Surgery: Advanced Characterization, Therapeutics, and Systems VIII
Graham M. Watson; Harvey Lui; Lou Reinisch; Penny J. Smalley; Kenneth Eugene Bartels; R. Rox Anderson; Lawrence S. Bass; Kenneth Eugene Bartels; C. Gaelyn Garrett; Lloyd P. Tate; Sharon L. Thomsen; Reza S. Malek; Aaron P. Perlmutter; R. Rox Anderson; Lawrence S. Bass; C. Gaelyn Garrett; Kenton W. Gregory; Harvey Lui; Reza S. Malek; Aaron P. Perlmutter; Lou Reinisch; Penny J. Smalley; Lloyd P. Tate; Sharon L. Thomsen; Graham M. Watson, Editor(s)

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