Matrix metallo-proteinases (MMPs) are often present in high levels in cancer such as tumors of the skin, breast, thyroid, cervix, lung, colon and prostate, but absent in normal tissues. MMPs are enzymes that are capable of chewing through the protein barriers that hold the primary tumor in its place. Once these barriers are degraded, the tumor can spread, or metastasize, throughout the body. We are designing a probe, to administer to the patient, that will remain invisible until it is degraded by the MMPs. After it is chewed in half, the probe will light up. We will capture and measure the light with optical imaging equipment and know that the tumor contains high levels of MMPs. The major pharmaceutical companies are currently developing drugs that will inhibit the action of the MMPs, thus slowing metastasis or stopping it altogether. If we are successful, the probe could be used to decide whether to initiate MMP inhibitor therapy and to monitor the therapy once it has begun. It could also be used to identify which tumors are likely to metastasize. The equipment used for optical imaging is relatively inexpensive and uncomplicated. A patient would likely be scanned at the office of their doctor. To test whether the probes will be effective in lighting up tumors we will perform the following Aims.
Aim 1 : The probes will be prepared from commercially available starting materials, separated from the starting materials if necessary, and tested for their purity Aim 2: Before testing in animal models, the probes will be tested in a variety of ways to show that they will indeed be chewed in half by MMPs and release the quantity of light needed to visualize a tumor growing in a living being. The stability and toxicity of the probes will be tested as well.
Aim 3 : Finally the probes will be tested in an animal model to see whether the tumors light up to an extent that the light is significant enough to be quantified. A variety of experiments (controls) will be used to make sure that the light observed is indeed due to MMP action and not from another source.
The goal of this research is to develop pharmaceuticals that are optically invisible until they encounter a tumor and light up in its presence. Ultimately, these agents will allow for rapid and non-invasive or minimally invasive diagnosis of cancer. ? ? ?
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