| A significant obstacle to improving the effectiveness of breast cancer chemotherapy has been that prediction models designed to test chemotherapy agents against tumor cell lines or biopsy specimens in the laboratory have been unsuccessful in identifying many cases of resistance to those agents that occur inside the body. Accurate predictors of early response to chemotherapy compounds may prove valuable in determining optional clinical management of patients with breast cancer. To that end, we have used positron emission tomography (PET) to visualize three chemotherapy agents (cyclophosphamide, paclitaxel, and 5-fluorouracil) labeled with radioactive fluorine (18 F) to non-invasively assess the distribution pattern and timing of how much of each chemotherapy agent goes into tumors and normal organs, how quickly, and for how long. The PET tracers had distribution patterns comparable to the unlabeled chemotherapy agents in analyzed tissues, and PET imaging measurements corresponded well with those analyses. We have also used the tracers in tumor-bearing animals, in conjunction with PET, to perform studies aimed at predicting chemotherapy response. The data suggest that PET measures of the tracers can be used to accurately reflect the fate of their corresponding chemotherapy agents. These tracers are thus promising agents for non-invasively predicting the relative amounts of the chemotherapy drug in the tumor and each organ at doses given for treatment, thereby helping to guide oncologists' selection, to individualize the optimal regimen for each patient. |
