Investigation of the Mechanisms of Radio-Dynamic Therapy

Purpose: Photodynamic therapy (PDT) uses light-activated drugs to treat diseases ranging from cancer to age-related macular degeneration and antibiotic-resistant infections.The fini e penetration depth of light has limited the clinical application of PDT.This work investigates the substitution of light in PDT using Cerenkov light induced by 45MV photon beams from the LA45 therapy accelerator.This new treatment technique has been named radio-dynamic therapy (RDT) and this paper investigates the dosimetric requirement of RDT.Method: Cerenkov light and its spectrum induced by 45MV x-ray beams from a LA45 therapy accelerator, was simulated with the Monte Carlo method.The excitation efficie y of Cerenkov light in RDT was theoretically studied and compared with the excitation efficie y of external laser light in PDT.Experiments were carried out to enhance the excitation efficie y for singlet oxygen production with specific coenzymes as substrates.These results were compared with previous experimental work reported in the literature.Results: Our Monte Carlo results showed that the intensity of Cerenkov light induced by 45MV photons from a LA45 accelerator was 5-8 times of that induced by 6MV photons from conventional radiotherapy accelerators.The excitation effect for the homogeneous internal Cerenkov light distribution induced by 3DCRT was over 10 times of that by external laser light that is nearly exponentially attenuated in conventional PDT.According to the Soret-Band resonance absorption theory, Cerenkov light induced by 45MV X-rays, which is peaked at 370 -430nm, can be 10-20 times more effective in activating PpIX to produce singlet oxygen than the 630nm laser light used in conventional PDT.Finally, the specific coenzyme enhanced excitation efficie y by 3 times.Furthermore, RDT is delivered with 3DCRT using 45MV photons from LA45 accelerators (3-6Gy/fraction, 1fraction/ week, 4~6weeks).This fractionated radiotherapy had a synergetic effect on the outcome of Cerenkov-induced PDT. Conclusion:Our results indicated that the light dose and fluen e rate of RDT using Cerenkov light from 45MV x-rays was comparable to that in conventional PDT using the 630nm laser light.Combining the therapeutic effect of Cerenkov-induced PDT and the deep penetration and conformity of high-energy x-ray RT, RDT may be developed into a potential treatment modality for a wide range of cancers at various stages as well as for other diseases.