Broadband reflectance measurements of light penetration, blood oxygenation, hemoglobin concentration, and drug concentration in human intraperitoneal tissues before and after photodynamic therapy

Abstract

We evaluate Photofrin-mediated photodynamic therapy (PDT) in a phase 2 clinical trial as an adjuvant to surgery to treat peritoneal carcinomatosis. We extract tissue optical [reduced scattering (mu(s)'), absorption (mu(a)), and attenuation coefficients (mu(eff))] and physiological [blood oxygen saturation (%S(t)O2), total hemoglobin concentration (THC), and photosensitizer concentration (c(Photofrin))] properties in 12 patients using a diffuse reflectance instrument and algorithms based on the diffusion equation. Before PDT, in normal intraperitoneal tissues %S(t)O2 and THC ranged between 32 to 100% and 19 to 263 microM, respectively; corresponding data from tumor tissues ranged between 11 to 44% and 61 to 224 microM. Tumor %S(t)O2 is significantly lower than oxygenation of normal intraperitoneal tissues in the same patients. The mean (+/-standard error of mean) penetration depth (delta) in millimeters at 630 nm is 4.8(+/-0.6) for small bowel, 5.2 (+/-0.67) for large bowel, 3.39(+/-0.29) for peritoneum, 5.19(+/-1.4) for skin, 1.0(+/-0.1) for liver, and 3.02(+/-0.66) for tumor. c(Photofrin) in micromolars is 4.9(+/-2.3) for small bowel, 4.8(+/-2.3) for large bowel, 3.0 (+/-1.0) for peritoneum, 2.5(+/-0.9) for skin, and 7.4(+/-2.8) for tumor. In all tissues examined, mean c(Photofrin) tends to decrease after PDT, perhaps due to photobleaching. These results provide benchmark in-vivo tissue optical property data, and demonstrate the feasibility of in-situ measurements during clinical PDT treatments.