Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-5-12
pubmed:abstractText
Photosensitizer biodistribution change inside tissue is one of the dominant factors in photodynamic therapy efficacy. In this study, the pharmacokinetics of a benzoporphyrin derivative (BPD), delivered in verteporfin for injection formulation, have been quantified in the rat Dunning prostate tumor MAT-LyLu model, using both subcutaneous and orthotopic sites. Blood plasma sampling indicated that BPD had a bi-exponential metabolic lifetime in vivo, with the two lifetimes being 9.6 min and 8.3 h. The spatial distributions in the tumor were quantified as a function of distance from the perfused blood vessels, using fluorescence histologic images of the tumor. A fluorescent vascular marker was used to obtain locations and shapes of perfused capillaries at a wavelength of emission different from that of BPD and to allow colocalized images to be acquired of vessel and BPD locations. Using the BPD fluorescence images obtained 15 min after intravenous administration, a forward finite-element solution to the diffusion equation was used to predict the drug distribution by matching the fluorescence intensity images observed microscopically. An inverse solver was used to minimize the root mean square error between the image of simulated diffusion and the experimental image, resulting in estimation of the diffusion coefficient of BPD in the tumor models. Effective diffusion coefficients were 0.88 and 1.59 microm2/s for the subcutaneous and orthotopically grown tumors, respectively, indicating that orthotopic tumors have significantly higher vascular extravasation rates as compared with subcutaneous tumors. This analysis supports the hypothesis that leakage rates of the photosensitizer vary considerably. Thus, although varying the time between injection and optical irradiation may be used to vary the targeting between vascular and less vascular areas, the precise time of treatment will depend on the nature of the permeability of the vasculature in the tissue being treated.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0031-8655
pubmed:author
pubmed:issnType
Print
pubmed:volume
79
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
323-31
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Analysis of effective molecular diffusion rates for verteporfin in subcutaneous versus orthotopic Dunning prostate tumors.
pubmed:affiliation
Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.