- 學位論文
無線射頻光源系統研發應用於倉鼠口腔前期癌病變的體內光動力治療
Development of RF light emission system for PDT studies on hamster oral precancerous lesions
摘要
光動力療法（photodynamic therapy, PDT）是一項在口腔癌治療上很受看好的輔助治療方法。通常PDT都是使用單次高光劑量（single high light dose, SHLD）照射治療，亦有文獻報導，分次低光劑量(fractionated low light dose, FLLD)重複治療更具療效，因此本研究提出運用射頻(radio frequency, RF)光照系統治療倉鼠囊頰口腔前期癌的構想，探討以此射頻光照系統結合FLLD治療模式於臨床應用之可行性。射頻光照系統含有一配對之射頻電源輸送器與小型光照器。倉鼠的實驗是將小型光照器置入罹有前期癌的倉鼠囊頰，以射頻電源輸送器施予電能，驅動光照進行週期（七天）治療。研究項目包括射頻系統之光照功率、射頻電源輸送器與小型光照器之垂直與側向位移試驗、光源波長驗證、溫升試驗、倉鼠動物模型驗證以及倉鼠光動力治療之實驗。結果顯示，在射頻電源輸送器提供2.1 V的電壓時，光照器之光功率可穩定輸出20 mW/cm2，電源輸送器與光照器之間的側向位移需控制於1公分之內，垂直位移則需控制於0.5公分內。由光譜儀確認光照波長為635±5 nm，適用於5-ALA光感藥物，繼以切片與光動力診斷法證實倉鼠口腔前期癌之誘發成功。在治療中，倉鼠口腔平均溫升約為5.1±2.8℃。實驗結果顯示，口腔前期癌倉鼠經FLLD模式治療之恢復情況以及治療週期（2.2）皆優於SLLD治療模式（2.7）；SHLD治療模式（3.6）雖有其成效，但在治療口腔前期癌與復原口腔組織的效益較之SLLD為遜色。總言之，所製作之射頻光照系統在動物模式上確有治療口腔前期癌之成效，具有臨床應用之潛能。
並列摘要
Photodynamic therapy (PDT) is a promising adjuvant therapy to treat oral cancers. PDT is commonly performed with single high light dose (SHLD) exposure. Some literatures, however, reported that fractionated low light dose (FLLD) PDT is more effective in cancer treatment. This study proposes utilizing implantable light devices drivable by radio frequency (RF) transmitters to treat oral pre-cancer in hamster pouches to explore if the RF technique in conjunction with the FLLD is feasible to be used in clinical applications. A lighting system consisting of a miniature light device and an RF transmitter was first completed. The miniature light device was placed into a hamster pouch, where existed oral pre-cancer. It was then powered by the RF transmitter to perform the 5-ALA/PDT study. Treatment responses such as complete response and partial response and the course of treatment (7 days per treatment cycle) were defined as the outcome indexes to examine the study performance. The tasks studied in this work included (1) the fluence rate from the light device versus the voltage applied in the RF transmitter, (2) the limitation of the vertical and lateral displacements between the light device and the RF transmitter, (3) the confirmation of the wavelength (635±5 nm) from the light devices, (4) the determination of optimal time period to perform the PDT after the 5-ALA administration, (5) thermal increasing in performing the study, and (6) the comparison of the oral pre-cancer response in the hamsters treated by the 5-ALA/PDT procedures among the modes of FLLD, SHLD, and single low light dose (SLLD). The results show that a light fluence rate of 20-mW/cm2 by the implantable light device can be driven by a voltage of 2.1 V from the RF transmitter. To be able to properly utilize the lighting system, the lateral and vertical displacements must limit within 1.0 and 0.5 cm, respectively. The wavelengths outputted from the light devices were all in compliance with the demand. The most appropriate time to illuminate light for the hamster PDT study was 2.5 hours after the 5-ALA administration. During the period of performing the animal study, the oral temperature increase was 5.1±2.8℃ on average. The study results show that the treatment response and the course of treatment by the FLLD mode (2.2 cycles) were all superior to that by the SLLD (2.7 cycles) mode. Though applying the SHLD (3.6 cycles) mode in this study shows the treatment effectiveness, its performance from the point of view of complete response as well as inhibiting pre-cancer re-occurrence was no better than the SLLD mode. In conclusion, the developed RF lighting system facilitating the 5-ALA/PDT treatment for the oral pre-cancer with the FLLD mode shows promising results. It has a great potential to be utilized in the clinical applications.