This item is under embargo and not available online per the author's request. For access information, please visit http://libanswers.wustl.edu/faq/5640.
Date of Award
Doctor of Philosophy (PhD)
The goal of this dissertation is to evaluate the feasibility of applying 64Cu radiopharmaceuticals in diagnosis and therapy of cancers. 64Cu (T1/2 = 12.7 h) decays by both Ã¢+ (656 keV, 17.4%) and Ã¢- (573 keV, 17.4%) particles, which enable simultaneous diagnostic positron emission tomography (PET) imaging and radiotherapy. A new cross-bridged macrocyclic bifunctional chelator for64Cu, CB-TE1A1P, was conjugated to the somatostatin analogue Y3-TATE and the epidermal grow factor receptor (EGFR)-targeting mAb cetuximab. CB-TE1A1P-Y3-TATE was radiolabeled with64Cu in high purity and high specific activity using mild conditions. The biological behavior of64Cu-CB-TE1A1P-Y3-TATE is compared to64Cu-CB-TE2A-Y3-TATE in SSTr2-positive rat pancreatic AR42J cells and tumor-bearing rats.64Cu-CB-TE1A1P-Y3-TATE boasted improved blood clearance than 64Cu-CB-TE2A-Y3-TATE, as well as lower accumulation in other non-target organs such as liver, lung and bone.64Cu-CB-TE1A1P-cetuximab was evaluated as a targeted radiopharmaceutical for PET imaging and potentially radioimmunotherapy of tumors overexpressing EGFR in human colorectal tumor HCT116 cells and tumor bearing mice. As the first cross-bridged bifunctional chelator developed for labeling antibody with64Cu, CB-TE1A1P enabled radiolabeling cetuximab at mild conditions and demonstrated great improvement over the traditional chelator DOTA due to the higher tumor to non-targeting organ ratios.64Cu labeled DOTA-cetuximab demonstrated great survival benefit in p53 wild-type human colorectal tumors.64Cu specifically delivered to EGFR-positive tumor by cetuximab can suppress tumor growth despite of the KRAS status. These data together provide insight into applications of64Cu radiopharmaceuticals for oncologic imaging and therapy.
Chair and Committee
Carolyn J Anderson
John-Stephen Taylor, Joseph Ackerman, Liviu Mirica, Buck E Rogers, Gary Patti
Guo, Yunjun, "Copper-64 Radiopharmaceuticals for Oncologic Imaging and Therapy" (2012). Arts & Sciences Electronic Theses and Dissertations. 160.
Available for download on Sunday, May 15, 2112