Analysis of effective molecular diffusion rates for verteporfin in subcutaneous versus orthotopic Dunning prostate tumors

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.     

Absorption and scattering imaging of tissue with steady-state second-differential spectral-analysis tomography

A novel approach to reconstructing both the absorption and the scattering properties of a turbid medium simultaneously from steady-state broadband spectral measurements is presented that utilizes second-differential fitting to the water spectrum to estimate the optical path length in tissue. Theoretical and experimental evidence is provided to demonstrate the robust accuracy of the spectroscopy approach and reconstructed absorption images. The steady-state broadband CCD system has the potential to provide accurate chromophore imaging without the technological complexity of time- or frequency-domain systems.     

Rotating sector study of the gas phase photochlorination of 2,2-dichloro-1,1,1-trifluoroethane

The rate constant for the combination of 2,2-dichloro-1,1,1-trifluoroethyl radicals has been measured by applying the rotating sector technique to the gas phase photochlorination of 2,2-dichloro-1,1,1-trifluoroethane at 315°K. The observed value is 6.89 × 10¹² cc/mole.sec. This value is in excellent agreement with measurements by Wampler and Kuntz which yielded a temperature-independent value of 6.6 × 10¹² cc/mole.sec. The measurement by Wampler and Kuntz was determined from the photochemical system (CF₃CCl₃ + C-C₆H₁₂ + hν). The Arrhenius parameters for the reaction CF₃CCl₂· + Cl₂ → CF₃CCl₃ + Cl were found to be given by the expression log k₃ = 12.10 ? 5830/2.3RT (units in mole, cc, and sec). This is a relatively high activation energy for a chlorination reaction and makes the reaction ever slower than the chlorination of chloroform.