Determination of the distribution of light, optical properties, drug concentration, and tissue oxygenation in-vivo in human prostate during motexafin lutetium-mediated photodynamic therapy

Abstract

It is desirable to quantify the distribution of the light fluence rate, the optical properties, the drug concentration, and the tissue oxygenation for photodynamic therapy (PDT) of prostate cancer. We have developed an integrated system to determine these quantities before and after PDT treatment using motorized probes. The optical properties (absorption (micro(a)), transport scattering (micro(s'), and effective attenuation (micro(eff)) coefficients) of cancerous human prostate were measured in-vivo using interstitial isotropic detectors. Measurements were made at 732 nm before and after motexafin lutetium (MLu) mediated PDT at different locations along each catheter. The light fluence rate distribution was also measured along the catheters during PDT. Diffuse absorption spectroscopy measurement using a white light source allows extrapolation of the distribution of oxygen saturation StO2, total blood volume ([Hb]t), and MLu concentration. The distribution of drug concentration was also studied using fluorescence from a single optical fiber, and was found to be in good agreement with the values determined by absorption spectroscopy. This study shows significant inter- and intra-prostatic variations in the tissue optical properties and MLu drug distribution, suggesting that a real-time dosimetry measurement and feedback system for monitoring these values during treatment should be considered in future PDT studies.

Optimized interstitial PDT prostate treatment planning with the Cimmino feasibility algorithm

“…We have previously shown that the human prostate has an inhomogeneous light-opacity distribution in vivo, which calls into question some of these assumptions. 12,13 A number of optimization algorithms used in brachytherapy are of interest for prostate photodynamic therapy. The most common ones are simulated annealing algorithms [14][15][16] and genetic algorithms.…”

Prostate PDT dosimetry

“…Fig. 6(b) shows measured distribution of MLu drug concentration in prostate determined by absorption measurements at 732 nm, absorption spectroscopy measurements (see below) and fluorescence measurements [58]. The results of the three methods agree well for MLu drug concentration.…”

“…RUQ: right upper quadrant; LUQ: left upper quadrant; RLQ: left lower quadrant (taken from Ref. [58]). 3D reconstructed optical properties ((a) μ a and (b) ) at 732nm in human prostate before MLu-mediated PDT.…”

“…As a result, fluence rates can be measured at a variety of distances from the point source, and the resulting profile can be used to determine the prostate optical properties. By moving the source to various positions, we can map the distribution of optical properties throughout the organ [58]. Fig.…”

“…Early PDT clinical protocols only specify this quantity in terms of the amount of photosensitizer given to patient per body weight. Recent in vivo studies have shown large variation of photosensitizer concentration in different tissue types, thus suggesting determination of this quantity in vivo in the region of treatment directly [22,58]. To include the drug concentration in the evaluation of PDT dose, in situ fluorescence [59] or absorption [39,[60][61][62][63] measurements of photosensitizer can be made interstitially using optical fibers.…”