Abstract 4341: A novel injectable polymer liquid that self-assembles into radioactive “seeds” for brachytherapy.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Brachytherapy seeds are made by sealing radionuclides in metal or other non-degradable material (resin or glass) and surgically implanted into the tumor tissue. Brachytherapy has shown some efficacy in the clinic for the treatment of solid tumors. However, its application and efficacy is limited due to the side effects caused by seed migration locally and systemically, limited antitumor efficacy because of spatial heterogeneity of the dose distribution, and complicated surgical procedure for implantation and seed removal. In an attempt to overcome these drawbacks, using thermally sensitive elastin-like polypeptide (ELPs), we have developed an injectable polymer that is attached to a radioactive isotope, and that upon injection as a liquid into a tumor spontaneously assembles into a radioactive seed and destroys the tumor by radiation from the inside-out. To do so, we designed and synthesized an ELP for this study that is soluble at room temperature but rapidly collapses into a viscous coacervate upon warming to body temperature. Our latest study results revealed the following advantages of this ELP radionuclide seeds for an alternative formula for brachytherapy. 1) The fluorescence imaging of ELP seeds in tumors exhibited a uniform distribution of ELP seeds in the tumor interstitium and showed that all the ELP seeds were limited within the tumor mass when ratio of the tumor to injection volume was not more than 2.5. This result indicates that the tumor coverage or leakage of ELP seeds is partially dependent on the injection volume; 2) there is no less than 50% of the injection 131I radioactivity in this ELP seeds retained in tumor one week after infusion; 3) the brachytherapy of the ELP radionuclide seeds achieved a significant tumor efficacy in both FaDu and PC-3 human tumor in nude mice, leading to > 67 % tumor cure, even when the initial tumor size was up to 500 mm3 when a bolus intratumoral administration of 131I-ELP seeds at a dose of 2000 μCi/150mm3; 4) it had minimal toxicity, because no animal body weight lost >15% of the initial; 5) it showed no evidence of either systemic or local leakage of the seeds or seed migration, because no any important organ or skin or muscle surrounding tumor had > 0.5% ID/g 24 hr. post-infusion in biodistribution study. In addition, in an orthotopic prostate model, the ELP seeds achieved markedly antitumor efficacy and had no evidence showing severe toxicity. In summary, these ELP seeds are injectable as a radioactive liquid that self-assemble in vivo into viscous ‘seeds’ that remain within the tumor mass, irradiate the tumor from the inside-out with good efficacy in multiple tumor models, and biodegrade within a week to a month with non-toxic amino acid by-products that are resorbed. These features suggest them as a compelling alternative to current approaches to brachytherapy. Citation Format: Wenge Liu, Jonathan R. McDaniel, Xinghai Li, Jeffery Schaal, Jayanta Bhattacharyya, Michael R. Zalutsky, Ashutosh Chilkoti. A novel injectable polymer liquid that self-assembles into radioactive “seeds” for brachytherapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4341. doi:10.1158/1538-7445.AM2013-4341