A heterogeneous optimization algorithm for reacted singlet oxygen for interstitial PDT.

Abstract

Singlet oxygen (1O2) is the major cytotoxic agent for type II photodynamic therapy (PDT). The production of 1O2 involves the complex reactions among light, oxygen molecule, and photosensitizer. From universal macroscopic kinetic equations which describe the photochemical processes of PDT, the reacted 1O2 concentration, [1O2]rx, with cell target can be expressed in a form related to time integration of the product of 1O2 quantum yield and the PDT dose rate. The object of this study is to develop optimization procedures that account for the optical heterogeneity of the patient prostate, the tissue photosensitizer concentrations, and tissue oxygenation, thereby enable delivery of uniform reacted singlet oxygen to the gland. We use the heterogeneous optical properties measured for a patient prostate to calculate a light fluence kernel. Several methods are used to optimize the positions and intensities of CDFs. The Cimmino feasibility algorithm, which is fast, linear, and always converges reliably, is applied as a search tool to optimize the weights of the light sources at each step of the iterative selection. Maximum and minimum dose limits chosen for sample points in the prostate constrain the solution for the intensities of the linear light sources. The study shows that optimization of individual light source positions and intensities is feasible for the heterogeneous prostate during PDT. To study how different photosensitizer distributions as well as tissue oxygenation in the prostate affect optimization, comparisons of light fluence rate were made with measured distribution of photosensitizer in prostate under different tissue oxygenation conditions.