PhotoPoint photodynamic therapy with local drug delivery eliminates vessel wall cells in arteriovenous graft models.
OBJECTIVE
To demonstrate the feasibility of PhotoPoint photodynamic therapy (PDT) with local drug delivery, optimize dosimetry in a rabbit jugular vein model, and investigate its ability to deplete potential neointimal precursor cells in the vessel wall in a canine arteriovenous graft (AVG) model.


METHODS
Photosensitizer MV2101 was administered locally in rabbit veins, incubated for 0-40 min and activated with external laser light. In canine veins, MV2101 was incubated for 30 min and activated by light. Tissues were excised at acute and chronic timepoints.


RESULTS
PhotoPoint PDT reduced cell populations in both models with maximum depletions occurring at 20 min (> or = 100 J/cm2) in rabbit veins (> 90% depletion) and 30 min (200 J/cm2) in canine veins (> 85% depletion). Chronic veins revealed no evidence of PhotoPoint PDT-related abnormalities.


CONCLUSIONS
PhotoPoint PDT with local MV2101 dramatically depleted potential neointimal precursor cells in the vessel wall. This suggests local drug delivery is feasible and that PhotoPoint PDT may be an efficacious treatment that could prolong AVG patency in the clinic.
Burgher
Julie M
JM
Miravant Medical Technologies, 336 Bollay Drive, Santa Barbara, CA 93117-5550, USA.
Barton
Jennifer M
JM
Farooq
Michael M
MM
Vasek
Jeff
J
Scott
Robert W
RW
Freischlag
Julie A
JA
Grove
Robert I
RI
D000818:Animals; D001166:Arteriovenous Shunt, Surgical; D001807:Blood Vessel Prosthesis; D002452:Cell Count; D004195:Disease Models, Animal; D004285:Dogs; D016503:Drug Delivery Systems; D005240:Feasibility Studies; D007601:Jugular Veins / Q000187:drug effects* / Q000528:radiation effects* / Q000648:ultrastructure; D008297:Male; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D011817:Rabbits; D011874:Radiometry; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects* / Q000528:radiation effects* / Q000648:ultrastructure; D014654:Vascular Patency / Q000187:drug effects / Q000528:radiation effects
D017319:Photosensitizing Agents