This project will develop new radiopharmaceutical probes and new applications for established imaging agents to maintain a pipeline of new PET imaging strategies for assessing cancer and its response to therapy These are four projects that could complement our overall goal of imaging important characteristics of the tumor phenotype and move toward translation to human studies within five years. Our first objective is to develop imaging of HER2/neu, an important target for therapy of breast cancer. W( will compare two approaches. The first involves labeling of trastuzumab, the antibody that has therapeutic value in some patients with breast cancer, with a long-lived positron emitter, [89]Zr. We will also label a low M Antibody to the same target with [18]F following two methods and compare these imaging agents in human cell lines and mouse models that express HER2, including some control studies. One the challenges of imaging androgen receptor (AR) expression through its ligands Is the enzymatic metabolism and catabolism of these steroids.
This aim will combine the pre-clinical expertise and animal models of prostate researchers at UW and chemistry expertise of J Katzenellenbogen to develop and test better imaging agents for testing of AR activity in the prostate. [64]Cu]ATSM is an alternative hypoxia imaging agent that we will compare with FMISO through chemistry cell culture and animal studies designed to distinguish the copper reduction reaction in tissues from the basic coordination chemistry of copper with ATSM. The literature mechanism is incomplete in that it fails to account for variability of uptake with tumor type and does not reconcile an observed paradoxical increase in CuATSM uptake as PO2 is returned to normal after an episode of hypoxia;FMISO appropriately decreases when PO2 i normal. We will test the hypothesis that CuATSM retention is reflecting thiol redox and, as such, is complementary to FMISO. This project will also evaluate a brain PET radiopharmaceuticals from the literature that might be applied to unique cancer studies locally. The Prostate SPORE is interested in a new therapy directed at monoamine oxidase A for which there is a known imaging agent, [11]C]clorgyline. We will use cellular and small animal studies to evaluate its potential for imaging prostate cancer to eventually test whether inhibiting this enzyme will synergize with chemotherapy.

Public Health Relevance

This research project is important to replenish the pipeline of new imaging agents selected in collaboration with our cancer colleagues for their potential to answer important clinical questions. PET agents for imaging HER2, an important target in breast cancer, will be developed and tested. Another collaboration will provide a unique opportunity to develop better AR imaging agents. Some critical tests comparing two potential hypoxia imaging agents are planned and an established PET agent for imaging the brain will be evaluated for selecting subjects for a new targeted therapy for prostate cancer. All of these radiopharmaceuticals would provide valuable imaging tools to support translational cancer research

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA042045-24
Application #
8566992
Study Section
Special Emphasis Panel (ZCA1-RPRB-K)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
24
Fiscal Year
2013
Total Cost
$235,725
Indirect Cost
$70,494
Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Fowler, Amy M; Clark, Amy S; Katzenellenbogen, John A et al. (2016) Imaging Diagnostic and Therapeutic Targets: Steroid Receptors in Breast Cancer. J Nucl Med 57 Suppl 1:75S-80S
Kurland, Brenda F; Muzi, Mark; Peterson, Lanell M et al. (2016) Multicenter Clinical Trials Using 18F-FDG PET to Measure Early Response to Oncologic Therapy: Effects of Injection-to-Acquisition Time Variability on Required Sample Size. J Nucl Med 57:226-30
Muzi, Mark; Krohn, Kenneth A (2016) Imaging Hypoxia with ¹⁸F-Fluoromisonidazole: Challenges in Moving to a More Complicated Analysis. J Nucl Med 57:497-8
Currin, Erin; Peterson, Lanell M; Schubert, Erin K et al. (2016) Temporal Heterogeneity of Estrogen Receptor Expression in Bone-Dominant Breast Cancer: 18F-Fluoroestradiol PET Imaging Shows Return of ER Expression. J Natl Compr Canc Netw 14:144-7
Kurland, Brenda F; Peterson, Lanell M; Lee, Jean H et al. (2016) Estrogen Receptor Binding (18F-FES PET) and Glycolytic Activity (18F-FDG PET) Predict Progression-Free Survival on Endocrine Therapy in Patients with ER+ Breast Cancer. Clin Cancer Res :
Wolsztynski, E; O'Sullivan, F; O'Sullivan, J et al. (2016) Statistical assessment of treatment response in a cancer patient based on pre-therapy and post-therapy FDG-PET scans. Stat Med :
Link, Jeanne M (2015) Publish or perish…but where? What is the value of impact factors? Nucl Med Biol 42:426-7
Peck, M; Pollack, H A; Friesen, A et al. (2015) Applications of PET imaging with the proliferation marker [18F]-FLT. Q J Nucl Med Mol Imaging 59:95-104
Wangerin, Kristen A; Muzi, Mark; Peterson, Lanell M et al. (2015) Effect of (18)F-FDG uptake time on lesion detectability in PET imaging of early stage breast cancer. Tomography 1:53-60
Rockne, Russell C; Trister, Andrew D; Jacobs, Joshua et al. (2015) A patient-specific computational model of hypoxia-modulated radiation resistance in glioblastoma using 18F-FMISO-PET. J R Soc Interface 12:

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