A promising new approach to treating solid tumors with radiation was highly efficacious and minimally toxic to healthy tissue in a mouse model of cancer, according to data published in November 15, 2012 issue of Cancer Research, a journal of the American Association for Cancer Research.

Patients with solid tumors, including prostate cancer, are often treated using a clinical technique called brachytherapy. Brachytherapy involves the surgical implantation of radioactive ?seeds? within a patient?s tumor to expose the tumor cells to high levels of radiation while minimizing systemic toxicity, the negative side effects of radiation on the rest of the body. ?The use of brachytherapy is limited by several factors,? Lui said ?The most prominent factor is the need for surgical implantation and removal of the seeds. We set out to develop an alternative approach to brachytherapy that would eliminate the need for surgery.?

To mitigate the disadvantages associated with complex surgical implantation and subsequent device removal procedures, Wenge Liu, M.D., Ph.D., associate research professor of biomedical engineering atDuke University in Durham, N.Cand his colleagues generated an injectable substance, called a polymer, attached to a source of radioactivity that spontaneously assembled into a radioactive seed after being injected into a tumor. Thisalternative approach using a genetically encoded peptide polymer solution composed of a thermally responsive elastin-like polypeptide (ELP) radiolabeled with (131)I that self-assembles into radionuclide seeds upon intratumoral injection.

The formation of these nontoxic and biodegradable polymer seeds led to prolonged intratumoral retention (?85% ID/tumor 7 days postinjection) of the radionuclide, elicited a tumor growth delay in 100% of the tumors in two human xenografts (FaDu and PC-3), and cured more than 67% of tumor-bearing animals after a single administration of labeled ELP. These results suggest that in situ self-assembly of biodegradable and injectable radionuclide-containing polypeptide seeds could be a promising therapeutic alternative to conventional brachytherapy

In all mice transplanted with either a human head and neck cancer cell line or a human prostate cancer cell line, injection of the radioactive polymers into the growing tumors substantially delayed tumor growth. In more than 67% of the animals, the tumors were eradicated by a single injection. Further analysis indicated no signs that cells outside the tumor had been exposed to significant amounts of radiation in any of the animals injected with the radioactive polymers.

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?We believe that this approach provides a useful alternative to existing brachytherapy, which requires a complicated surgical procedure to implant the radioactive seeds,? Liu said. ?Moreover, these injectable seeds degrade after the radiation is exhausted, so they do not need to be surgically removed.?

For more information:

Liu W, McDaniel J, Li X, Asai D, Quiroz FG, Schaal J, Park JS, Zalutsky M, Chilkoti A. Brachytherapy using injectable seeds that are self-assembled from genetically encoded polypeptides in situ. Cancer Res. 2012 Nov 15;72(22):5956-65. doi: 10.1158/0008-5472.CAN-12-2127. [Abstract]

Photo: Wenge Lui, MD, PhD associate research professor of biomedical engineering. Photo credit: Duke University.

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