Anthracycline based therapy is a mainstay for many patients with solid tumor cancers. However, many of these tumors have variable levels of multiple drug resistance (MDR) transporters that reduce treatment effectiveness. The P-glycoprotein (Pgp) system specifically acts as a membrane pump to exclude anthracyclines and other common chemo therapeutics from intracellular accumulation. The activity of this transporter system can be up-regulated after exposure to anthracycline treatment and this is a suspected variable in treatment resistance and failure. In this project, we will quantify Pgp activity using a known transporter substrate, [[11]C]-verapamil, for tumor imaging. The uptake kinetics of this imaging agent can be used to quantify tissue Pgp activity when the tumor area under the curve from 0 to 20 min (AUC{0-20}) is normalized to the same AUC for blood. Imaging in sarcoma patients showed a range of [

Public Health Relevance

Many tumors have variable levels of multiple drug resistance (MDR) transporters: that reduce treatment effectiveness for some chemotherapy protocols. The P-glycoprotein (Pgp) system specifically acts as a membrane pump to exclude drugs from intracellular accumulation. In this project, we will quantify Pgp activity using a known transporter substrate, [[11]C]-verapamil, for tumor imaging. The uptake kinetics of this imaging agent can be used to quantify tissue Pgp activity as an important resistance factor. Imaging before treatment and after exposure to chemotherapy will measure the extent of acquired MDR and should be useful to modify chemotherapy

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA042045-23
Application #
8555450
Study Section
Special Emphasis Panel (ZCA1-RPRB-K (M1))
Project Start
1998-05-12
Project End
2016-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
23
Fiscal Year
2012
Total Cost
$118,254
Indirect Cost
$35,328
Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Link, Jeanne M; Krohn, Kenneth A; O'Hara, Matthew J (2017) A simple thick target for production of 89Zr using an 11MeV cyclotron. Appl Radiat Isot 122:211-214
Kurland, Brenda F; Peterson, Lanell M; Lee, Jean H et al. (2017) 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 23:407-415
Wangerin, Kristen A; Muzi, Mark; Peterson, Lanell M et al. (2017) A virtual clinical trial comparing static versus dynamic PET imaging in measuring response to breast cancer therapy. Phys Med Biol 62:3639-3655
Wolsztynski, E; O'Sullivan, F; O'Sullivan, J et al. (2017) Statistical assessment of treatment response in a cancer patient based on pre-therapy and post-therapy FDG-PET scans. Stat Med 36:1172-1200
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
Muzi, Mark; Krohn, Kenneth A (2016) Imaging Hypoxia with ยน?F-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; 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
Jackson, Pamela R; Juliano, Joseph; Hawkins-Daarud, Andrea et al. (2015) Patient-specific mathematical neuro-oncology: using a simple proliferation and invasion tumor model to inform clinical practice. Bull Math Biol 77:846-56
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

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