Intravital microscopic analysis of vascular perfusion and macromolecule extravasation after photodynamic vascular targeting therapy.
OBJECTIVE
Photodynamic therapy (PDT), involving the combination of a photosensitizer and light, is being evaluated as a vascular disrupting therapy and drug delivery enhancement modality based on its effects on vascular perfusion and barrier function. Since tumor vasculature is the common route for the delivery of both blood and therapeutic agents, it is important to compare the effects of PDT on blood perfusion and substance transport.


METHODS
Tumor blood cell velocity and the extravasation of high molecular weight dextran molecules were continuously monitored by intravital fluorescence microscopy for up to 60 min after PDT using three doses of verteporfin in the MatLyLu prostate tumor model.


RESULTS
PDT induced tumor perfusion disruption via thrombus formation. PDT using a higher dose of verteporfin was more effective in inhibiting blood perfusion while a lower dose verteporfin-PDT was more potent in enhancing dextran extravasation. The increase in dextran extravasation induced by PDT was dependent upon dextran molecular weight. A lower molecular weight dextran obtained a higher tumor accumulation after PDT than a higher molecular weight dextran.


CONCLUSIONS
PDT with verteporfin had different effects on tumor vascular perfusion versus the extravasation of macromolecules. Optimal PDT conditions should be adjusted based on the therapeutic application.
He
Chong
C
Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, 600 South 43rd Street, Philadelphia, Pennsylvania 19104, USA.
Agharkar
Priyanka
P
Chen
Bin
B
D000818:Animals; D019540:Area Under Curve; D001783:Blood Flow Velocity; D001808:Blood Vessels / Q000187:drug effects / Q000502:physiology*; D003911:Dextrans / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D008297:Male; D008856:Microscopy, Fluorescence; D008970:Molecular Weight; D010477:Perfusion; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000627:therapeutic use; D011166:Porphyrins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000098:blood supply; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced; D000077362:Verteporfin
D003911:Dextrans; D005456:Fluorescent Dyes; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D016650:Fluorescein-5-isothiocyanate