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Efficacy of ELP as an Intratumoral Depot for Radionuclide Therapy of PC-3 Prostate Cancer in an Orthotopic, Nude Mouse Model

dc.contributor.advisor Chilkoti, Ashutosh
dc.contributor.author Schaal, Jeffrey Laurence
dc.date.accessioned 2012-05-25T20:18:16Z
dc.date.available 2012-05-25T20:18:16Z
dc.date.issued 2012
dc.identifier.uri https://hdl.handle.net/10161/5534
dc.description.abstract <p>Brachytherapy has emerged as one of the pre-eminent radiotherapy modalities for the treatment of prostate cancer. Current clinical methods utilize titanium encased radioactive seeds that are fixated within the prostate and permanently implanted. A novel brachytherapy alternative that has been developed to improve the delivery of radionuclide intratumorally is the synthetically designed elastin-like polypeptide (ELP). ELP can be injected in fluid form and undergoes an inverse phase transition to a biocompatible coascervate capable of serving as a biocompatible, intratumoral depot. Utilizing a previously developed ELP with a 7 tyrosine C-terminus tail, the therapeutic efficacy of ELP as a radioactive depot for treating prostate cancer was examined in a preclinical, orthotopic model. The orthotopic prostate model was first established by xenografting Bioware® PC-3M-luc-C6 cells into immunoincompetent, Balb/c nude mice. A non-invasive method for tracking tumor progression in vivo was developed using a correlation model comparing quantitative luminescent flux emitted from the cell line against the actual tumor size. The correlation between flux and tumor volume was determined to as Volume = 7.234x10-9x - 18.54, (±21.7%), where x is the supine photon flux measured from a 10 second exposure taken 18 minutes after D-luciferin injection. Radionuclide conjugation of 131I to ELP was conducted using the established IODO-GEN reaction methodology and mice were administered a therapeutic dose of 2mCi / 40µl ELP / 150 mm3 prostate tumor. Intratumoral deposition resulted in tumor regression in 90.9% of treated mice (n=11); 63.6% of which achieved tumor size reduction by over 60%. Radioactivity measurements demonstrate an 89.9% ELP depot retention over 2 weeks. Survival rates of the test group (64%) compared with controls (100%, n=14) indicate further testing is required to optimize radionuclide dosimetry.</p>
dc.subject Biomedical engineering
dc.subject Brachytherapy
dc.subject Elastin-like polypeptide
dc.subject Intratumoral Depot
dc.subject Phase transition
dc.subject Prostate Cancer
dc.subject Thermal sensitivity
dc.title Efficacy of ELP as an Intratumoral Depot for Radionuclide Therapy of PC-3 Prostate Cancer in an Orthotopic, Nude Mouse Model
dc.type Master's thesis
dc.department Biomedical Engineering


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