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US scientists have successfully predicted the outcome in treating breast tumours in a pre-clinical study of a so-called nano drug. Their research could help determine which patients will respond best to these and other drugs. Efstathios Karathanasis, Ravi Bellamkonda, Sri Balusu, and Kathleen McNeeley of the Wallace H. Coulter Department of Biomedical Engineering, at Georgia Institute of Technology, Sankararaman Suryanarayanan, Ioannis Sechopoulos, Andrew Karellas of the Department of Radiology and Winship Cancer Institute, at Emory University, Atlanta, and Ananth Annapragada of the School of Health Informatics, at the University of Texas Health Science Center, in Houston, publish details in the February issue of the journal Radiology. The researchers encapsulated an X-ray contrast agent, based on iodine, in 100-nanometre liposomes, materials akin to a microscopic soap bubble. The team then determined that a dose of 455 mg of iodine per kilogram of body mass was adequate to produce an undetectable signal in the blood while achieving enough accumulation in the tumour to produce a detectable signal at that site. Their hope was that they would be able to determine whether or not these drug carriers could enter rodent breast tumour cells following intravenous injection and to see what factors affected susceptibility. When they examined the rodents by X-ray digital mammography, they obtained good images of porous breast tumours which had absorbed the contrast agents. A poor image was indicative of contrast agents having failed to penetrate the tumour. Those animals that displayed superior images were associated with a better therapeutic response when the contrast agent was swapped for the anticancer drug doxorubicin. "We could tell in advance if the animals are good candidates for the treatment or not," explains team leader, Ananth Annapragada, an associate professor in health information sciences at Houston. With a liposome acting as a drug smuggler, the drug can enter leaky tumours through pores that are up to eight times the size of the liposome. "We found that different tumours light up differently," explains Annapragada, "The tumours that light up well take up the agent. Consequently, these are the tumours most likely to respond to liposomal doxorubicin." The team explains that higher uptake of the contrast agent by the tumour, suggests that the tumour has a more leaky system of blood vessels, which is associated with slower tumour growth. Slower growth rate, in turn, is usually associated with a better therapeutic outcome for administration of liposomal doxorubicin, the authors explain. Given that liposomal doxorubicin is designed to increase the amount of drug reaching a tumour it is important to know in advance of prescribing this expensive therapeutic whether it will ultimately benefit a patient. Currently, when an intravenous cancer drug is administered, very little reaches its intended target. The remaining drug circulates in the bloodstream and generally causes side-effects. The current clinical protocols for liposomal doxorubicin consist of a standard dose every three to four weeks, but with no prior knowledge of tumour vessel status, especially leakiness, dose scheduling could be misguided in some patients who are destined not to respond well but to suffer side-effects nevertheless. Moreover, the degree of tumour vasculature leakiness differs not only among tumours of the same type in different patients, but within a single tumour in the same patient. The contrast agent imaging of the tumour could thus provide insights into how best to dose the patient based on the exact structure of the tumour. "This new information could help personalize the treatment of cancer with liposomal doxorubicin," Annapragada adds. In addition to predicting the outcome of liposomal doxorubicin on breast tumours, liposomes might also be used to monitor the effects of an anticancer agent as it does its job. For such monitoring, the liposomes would be loaded not only with doxorubicin but also with a contrast agent. Tumour leakiness and drug uptake could then be observed simultaneously. The team published pre-clinical work on multifunctional liposomes in the journal Biomaterials in December 2008. Annapragada and fellow senior author Bellamkonda of GATech and Emory University are now involved with Houston start-up company Marval Biosciences working to translate these discoveries into patient diagnostics and prognostics. Related links:
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Assessing potential for success in doxorubicin chemotherapy |
