Most techniques used to treat cancer (other than chemotherapy) are directed against a defined tumor site in an organ, such as a brain tumor, or a tumor in the breast. When the mass of abnormal cells is consolidated and sufficiently large, either surgical removal, destruction of the tumor mass using either heat or cold, or radiation therapy becomes possible because the target is readily identifiable and localizable. However, it is not uncommon for a cancer that has initially occurred at a primary site to metastasize and spread into adjacent organs as diffuse clusters of abnormal cells. These small clusters of cells, which are more properly referred to as microscopic diffuse metastatic deposits, are not localizable and are virtually impossible to treat other than by chemotherapy. However, because of the diverse nature of cancer cells, only a portion of the metastatic abnormal cells will likely be susceptible to chemotherapy, leaving abnormal cells that are resistant to the therapy to multiply until the patient dies from the concomitant effects of the malignant cells.
This problem can arise, for example, when colorectal cancer occurs in a patient. Although the treatment applied to a cancerous tumor in the colon may be effective to destroy the tumor at that primary site, metastatic cancer cells often spread from this primary site into the liver (and into other organs of the body). Ultimately, because none of the conventional techniques for treating cancer are truly effective in destroying the microscopic metastasized cells, the patient will die when the liver ceases functioning due to the spread of the abnormal cells. Clearly, a new and more effective approach is required to destroy such microscopic diffuse non-localizable metastatic deposits in an organ that cannot be fully destroyed by any conventional treatment.
Recently, a new method for treating breast cancer has been developed by Eric Wachter et al. at Oak Ridge National Laboratory, and this method appears to be useful for treating other types of cancer. The technique employs a Ti:sapphire laser to administer PDT with light in the near infrared, i.e., relatively long, wavelength light. In conventional PDT, a light-activatable photoreactive agent is administered to a treatment site in or on a patient's body and is preferentially absorbed by abnormal cells at the site. When light from a laser or other source having a waveband corresponding to the absorption waveband of the photoreactive agent is applied to the abnormal cells, the photoreactive agent absorbs the light. The resulting photodynamic reaction then destroys the abnormal cells comprising the tumor.
The new technique developed by the Oak Ridge research group differs from conventional PDT in several respects. In contrast to conventional PDT, the near infrared light produced by the Ti:sapphire laser is at a wavelength substantially longer than the characteristic absorption waveband of the photoreactive agent employed. Instead of the single photon absorption process involved in a conventional photodynamic reaction, a two photon process occurs when a pulse of the 700-1000 nm light is focused on the tumor being treated. Due to its relatively long wavelength, the near infrared light emitted by a mode-locked Ti:sapphire laser can penetrate into tissue up to 8 cm. or more, making it possible to pinpoint tumors that are relatively deep within the patient's body, well below the dermal layer. The two photon process is able to activate a photoreactive agent such as psoralen, which is normally activated during PDT by ultraviolet light having a much shorter wavelength. Since light having a shorter wavelength penetrates a shorter distance into tissue, the long wavelength light is preferable. In addition, the longer wavelength light causes less damage to tissue than the shorter wavelength ultraviolet light normally used to activate psoralen.
In a paper entitled "Two-Photon Excitation of 4'-Hydroxymethyl-4,5', 8-Trimethylpsoralen," by Dennis H. Oh et al., Photochemistry and Photobiology, 1997, 65(1): 91-95, the magnitude of the emission spectrum of this specific psoralen when excited by two photon absorption is reported to depend quadratically on the intensity of the laser excitation. Based on this article, it appears that to be effective in causing an acceptable level of two photon absorption, a focused, high intensity light source must be used. Thus, it appears that although the technique developed by the Oak Ridge research group is useful in destroying cancer cells well below the surface of the patient's skin, a high power laser is required for producing the near infrared light and the laser must be aimed at a pinpoint location in an organ where a tumor is known to exist. It would therefore appear that this technique is not applicable to destroying diffuse, microscopic metastatic cells that have invaded an organ.
A different approach therefore seems to be required to achieve long wavelength, two photon excitation of an appropriate photoreactive agent to destroy abnormal cells that are randomly dispersed throughout an organ. Instead of using a high power light source, it will likely be possible to use a plurality of lower power light sources and to administer the light therapy for a long period of time. Preferably, if this PDT must be applied for an extended period of time, the patient should remain mobile during the treatment. A Ti:sapphire laser source clearly cannot be used for this purpose due to its expense, and the requirement that the patient remain motionless during the treatment with such a laser.