Radiation is extensively used for the treatment of cancer and other diseased cells and tissues. Radiation therapy consists of exposing part or all of the body to a field of ionizing electromagnetic radiation. Often performed at 1 MeV or higher, the goal is to damage diseased cells. Although healthy cells frequently receive high radiation doses during such treatment, the healthy cells, ideally, are better able to repair the damage and remain viable while the diseased cells die.
The effectiveness of conventional radiation therapy is limited by insufficient radiation dosing due to the need to reduce radiation to normal cells and tissues. In many cases, the radiation dose to a tumor is the same as the dose to other tissues, especially surrounding tissues. This leads to significant toxicity in healthy cells. In order to increase the ratio of the dose to the intended target versus normal tissue (non target), radiation is often introduced to the tumor from different angles to reduce injury to skin and overlying tissue. However the x-rays also spread beyond the tumor and overshoot the target. The result is significant toxicity to an organism due to dosing of normal tissues.
Contrast agents are used to enhance the effect of x-rays for treatment of aberrant tissue. (U.S. Pat. Nos. 6,125,295 and 6,366,801). For example, a contrast agent is normally delivered to a tumor mass prior to delivering the radiation dose. These contrast agents have, as a component, an element with a high atomic number (Z), such as iodine or gold. The interaction between the ionizing radiation and the greater cross-section of the high Z material creates additional ionizations that result in greater cell toxicity at the site of the tumor.
Contrast agents also improve the accuracy of assessing a disease state. To be useful, the contrast material must be delivered to the area where a suspected abnormality may be present for radiation exposure to result in high enough contrast for a successful diagnosis
However, conventional contrast agents have the disadvantage that they lack affinity for the cells and tissues to be treated so that the residence time of the agent in the targeted tissue is short. The poor uptake of the conventional contrast agent by a tumor means that the agent needs to be applied directly into the tumor. Furthermore, the contrast agents migrate out of the tumor quickly and delivery of the radiation is required very soon after administering the contrast agent, often within one hour. If delivered by intravenous administration, common contrast agents often require relatively large volumes of contrast agent solution to be administered within a short period of time e.g., 100 ml within one minute. This creates a risk of rapid allergic reaction and can cause discomfort to the patient.
To achieve more specific cellular and tissue targeting with these agents, they are typically modified using a biological carrier such as a protein, or a monoclonal antibody, or fragments thereof. Thus a monoclonal antibody combined with a payload of iodine or other heavy element can be used to more selectively deliver high Z atoms to a tumor. These agents have been shown to be useful for the treatment (when the elements themselves are radioactive isotopes) and diagnosis of cancers. However, the biodistribution of these systems is unfavorable to enhance radiation therapy when the elements are not radioactive. In addition, the retention time of the dose in blood when radioactive elements are used is long, and usually only a small portion of the dose is observed at the site of the tumor. Unfortunately, the density of antigen sites that the tumor can present is low and so the potential amount of high Z material that can be delivered is relatively low. Better agents are needed to enhance the effect of radiation at tumor sites.