The Theoretical And Experimental Study On The Tumor Oxygen Content In Photodynamic Therapy

A problem in the clinical PDT (Photodynamic Therapy) of tumors puzzles usincreasingly, i.e. the fastness of hypoxia tumor tissues. This problem is studied in thisdissertation theoretically and experimentally. In order to realize the measurement ofoxygen in tumor tissues, the first step is set to develop an equipment to measureoxygen in tissues.Fluorescence quenching measurement technology quantifies on the basis ofthe fluorescence time resolved spectrum but, in fact, oxygen is directly relevant to thetransition time that atoms of photosensitizer moves from high-energy to low-energy,i.e. fluorescence lifetime. Therefore, we probed in this problem thoroughly. Withtissue optics method, it is found that in our study the fluorescence lifetime indicatingoxygen content has something to do with the decay constant tod of the macrofluorescence time resolved spectrum. To be exact, it is exciting photons, fluorescencelifetime and fluorescence photons together that determine the postponed flying out offluorescence photons. As a result, photons form a time distribution, which usuallyappears a trend to attenuate with time. The decay constant is the very expression ofthis trend, which is the inner relationship the fluorescence lifetime and the decayconstant. What we benefit much from this study is that the result shows that tomeasure oxygen with fluorescence quenching,we should adopt photosensitizer withlong fluorescence lifetime. We collect and magnify fluorescence signals, with Pd-TCPP as photosensitizer indicating oxygen contend, 532nm continuous laser toactivate, and the tailor-made optic path and measurement devices. The demarcatingtest indicates homemade oxygen-measuring devices are reliable.We build a dynamic model of oxygen content in PDT of tumors, which dealswith the inner mechanism of photodynamic reaction, oxygen diffusing, oxygenconsuming by metabolism, oxygen supply, static oxygen distribution, geometricmodels of tumors, photo dynamic oxygen consuming, critical conditions etc, andincludes nearly all problems related to oxygen in PDT. The model is resolved byCrank-Nicolson discrete approach and relevant C++ programs are programmed. Whatthe resolved results show are as follows:1. Photodynamic process works only in high-oxygen areas near blood vessels butdoesn't in outside areas where oxygen content is less than some value Cth. Afterthe reaction works for a considerably long time, oxygen content in the wholetumor tissue will keep a constant value Cth, then the tumor will be in abalanceable metabolizing state, while photodynamic process will stop.2. It is commonly acknowledged that in same conditions, therapy under lowerfluency rate is more effective than that under higher fluency rate, but to explainit can only be started with reducing blood vessels damage to maintain oxygensupply.3. With lower initial oxygen density, the area of the tumor tissue participating inphoto dynamic reaction is smaller than the initial oxygen density, whichindicates PDT is less effective in that condition.4. With lower initial oxygen density, fractional lighting is less effective thancontinuous lighting, which, however, doesn't to apply to situations with higherinitial oxygen density.With animal experiments, parts of the conclusions above are validated.Observing tumor tissue slices taken from rats, it is found that damage to high-oxygenis more than that to low-oxygen. Tumor growth assay experiment shows that it takes alonger time for high-oxygen tumor in rats to double its volume than low-oxygentumor does, and when the initial oxygen content is lower than a certain value, the timetumor doubles its volume is near or less than 1.1 times as much as that of controlgroup, which shows the therapy is a failure. From the growth assay experiment offractional lighting group it is found that with higher initial oxygen, fractional lightingcan not lengthen the time tumor doubles its volume, but with lower initial oxygen, esp.with continuous lighting being ineffective, fractional lighting can improve the therapymarkedly.The innovation of this dissertation can be summarized as follows:1. The inner relationship between the fluorescence lifetime and the decayconstant of the fluorescence time resolved spectrum has been discovered.2. A experimental instrument suitable to measure the tissue oxygen has beendeveloped.3. A dynamic model of oxygen content in PDT of tumors has been built andsome original views described above have been concluded through the resolution ofthe model.4. Some of the conclusions have been proved through a designed animalexperiment.