In 2011, approximately 33,720 American men will die of prostate cancer. Clearly, there is an urgent need for new treatment options, as well as new methods for selecting the right treatment for each patient, and new ways to determine quickly if a patient is going to thrive after therapy, or if he will eventually succumb to disease relapse. Non-invasive imaging methods, in particular positron emission tomography (PET) which is now widely used in clinical oncology, are especially valuable because they avoid difficult and often expensive procedures that require direct manipulation of the cancer in the prostate. Because cancer is difficult to cure, the chance of success can be higher when patients are given two or more anti-cancer agents at the same time. However, this approach has not worked (well) for prostate cancer patients. We suggest a new approach for treating prostate cancer patients, because we believe two commonly used anti-cancer drugs (one that restricts tumor blood supply, and one that inhibits cancer cell growth) interfere with each other when given simultaneously. We believe this problem can be solved, and a new and better treatment found, simply by giving the two drugs one after the other (i.e., sequentially). We predict that this approach will do a much better job in killing prostate cancer cells (without killing non-cancerous cells). The experiments in our proposal will test this idea in mice. To make our studies more efficient, we have developed new ways to image cancer growth with PET, which will be used to determine whether our new therapy succeeds or fails in each individual tumor-bearing mouse. Thus, we feel we can make a unique and important contribution which can lead to better treatment options for prostate cancer patients. To test our hypothesis in small animal tumor models, we will first optimize the chemistry and select the best imaging agent and tumor model for subsequent experiments. Next, we will determine whether treatment shrinks or stops growth of prostate cancer cells injected under the mouse skin. Then, we will determine whether treatment shrinks or stops growth of prostate cancer cells injected into the bone of mice. These experiments are critical, because they address the most common and most serious scenario in human prostate cancer, when aggressive late stage prostate cancer invades human bone. This is known as metastatic prostate cancer and is lethal. In the last part of our study, we will compare cancer growth and measure treatment success when two anti-cancer drugs are given sequentially or concurrently. Non-invasive imaging will be used before, during and after treatment. Tissue samples will also be examined directly under the microscope, to confirm the results obtain by non-invasive imaging. If successful, this work will provide information that can be immediately applied to guide future clinical trials in prostate cancer, which can quickly lead t a paradigm shift in prostate cancer patient management. The same approach and our novel imaging agents can also help patients with other solid tumor types.

Public Health Relevance

The proposed work will test a new combination therapy strategy for treating metastatic prostate cancer. If successful, this work will provide critical information that can be immediately applied to guide future clinical trials in prostate cancer, which can quickly lead to a paradigm shift in prostate cancer patient management. Similar therapeutic approach, as well as the novel imaging agents developed here, can also be applicable to many other solid tumors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA169365-01A1
Application #
8454068
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Menkens, Anne E
Project Start
2013-04-12
Project End
2016-03-31
Budget Start
2013-04-12
Budget End
2014-03-31
Support Year
1
Fiscal Year
2013
Total Cost
$301,809
Indirect Cost
$94,309
Name
University of Wisconsin Madison
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Chen, Feng; Goel, Shreya; Hernandez, Reinier et al. (2016) Dynamic Positron Emission Tomography Imaging of Renal Clearable Gold Nanoparticles. Small 12:2775-82
Im, Hyung-Jun; England, Christopher G; Feng, Liangzhu et al. (2016) Accelerated Blood Clearance Phenomenon Reduces the Passive Targeting of PEGylated Nanoparticles in Peripheral Arterial Disease. ACS Appl Mater Interfaces 8:17955-63
Huang, Haoyuan; Hernandez, Reinier; Geng, Jumin et al. (2016) A porphyrin-PEG polymer with rapid renal clearance. Biomaterials 76:25-32
England, Christopher G; Kamkaew, Anyanee; Im, Hyung-Jun et al. (2016) ImmunoPET Imaging of Insulin-Like Growth Factor 1 Receptor in a Subcutaneous Mouse Model of Pancreatic Cancer. Mol Pharm 13:1958-66
England, Christopher G; Ehlerding, Emily B; Cai, Weibo (2016) Imaging the Biodistribution and Performance of Transplanted Stem Cells with PET. J Nucl Med 57:1331-2
England, Christopher G; Rui, Lixin; Cai, Weibo (2016) Lymphoma: current status of clinical and preclinical imaging with radiolabeled antibodies. Eur J Nucl Med Mol Imaging :
Ehlerding, Emily B; Cai, Weibo (2016) Smaller Agents for Larger Therapeutic Indices: Nanoscale Brachytherapy with 177Lu-Labeled Gold Nanoparticles. J Nucl Med 57:834-5
Cheng, Liang; Shen, Sida; Shi, Sixiang et al. (2016) FeSe2-Decorated Bi2Se3 Nanosheets Fabricated via Cation Exchange for Chelator-Free (64)Cu-labeling and Multimodal Image-Guided Photothermal-Radiation Therapy. Adv Funct Mater 26:2185-2197
England, Christopher G; Im, Hyung-Jun; Feng, Liangzhu et al. (2016) Re-assessing the enhanced permeability and retention effect in peripheral arterial disease using radiolabeled long circulating nanoparticles. Biomaterials 100:101-9
Kamkaew, Anyanee; Sun, Haiyan; England, Christopher G et al. (2016) Quantum dot-NanoLuc bioluminescence resonance energy transfer enables tumor imaging and lymph node mapping in vivo. Chem Commun (Camb) 52:6997-7000

Showing the most recent 10 out of 93 publications