Clinical Translation of Hyperpolarized 13C Interstitial pH Imaging for Better Risk Stratification of Prostate Cancer
Abstract
Rationale: Prostate cancer is a disease with a notoriously variable course. Some prostate cancers are slow-growing, indolent tumors that will never progress or threaten the lives of the people who carry them. However, other prostate tumors are very aggressive, lead to widespread disease, and ultimately prove fatal. Treatment of these different types of cancer is also variable. For example, patients with the indolent tumors may undergo active surveillance, in which they do not undergo treatment. Instead, they will have blood tests and periodic imaging and biopsy to track whether their tumor is growing. In contrast, patients with the aggressive tumor types should undergo definitive treatment of their tumor, either with surgery or radiation. Unfortunately, differentiating between these types of disease is a major challenge in oncology, and some patients with low-grade tumors undergo unnecessary surgery or radiation (exposing themselves to potential side effects such as incontinence and impotence), while some patients who are on active surveillance have hidden aggressive tumors that will ultimately become life-threatening. The goal of this proposal is to develop new imaging methods to enable physicians to know whether their patients carry aggressive or indolent tumors. The new imaging method, which we term HP pH magnetic resonance imaging (MRI), tests the presence of acid in the tumors, which is known to be associated with aggressive tumors in animal models. We have optimized these methods in the laboratory and applied them in mouse models of prostate cancer, with the finding that the HP pH MRI exam is able to detect the presence of high-grade, potentially lethal prostate cancer. These preliminary data strongly suggest that this method would be feasible for detecting potentially lethal prostate cancer in men. The goal of this application is to test this new imaging method in men with prostate cancer. Objective: The hypothesis of this proposal is that the HP pH MRI exam is able to detect the presence of high-grade, potentially lethal prostate cancer. In order to test this, the exam will be performed in patients who are about to undergo prostatectomy. Following surgery, the gold standard pathology outcome will be compared against the imaging findings. Specific Aims: In Specific aim 1, we optimize the HP pH MRI method by refining the underlying chemistry, methodology, and image acquisition parameters. The net goal of these experiments is to develop a method that enables high-resolution, accurate, and nontoxic imaging in a manner that could be shared with other institutions. These experiments will be used to develop an application to allow regulatory approvals from the U.S. Food and Drug Administration in the form of an Investigational New Drug Application. In Specific Aim 2, we will apply this optimized imaging exam in 10 patients with newly diagnosed prostate cancer who are planning for radical prostatectomy. After prostatectomy, the imaging studies will be compared against the resulting gold standard pathology. We will then test whether the pH measured in the tumor correlates with the disease grade, as measured by the Gleason score. When completed, these experiments will demonstrate that the HP pH MRI method is capable of detecting high grade, potentially lethal prostate cancer, and therefore could be used in clinical protocols to help therapeutic planning. Ultimate Applicability of the Approach: What Type of Patients Will This help and How Will It Help Them? This method is designed to help patients with prostate cancer who have not yet undergone definitive therapy. The goal of this method is to detect clinically significant, potentially lethal disease, which would help a patient and physician select appropriate therapy. What Are the Potential Clinical Applications, Benefits, and Risks? The immediate clinical application is in men with newly diagnosed prostate cancer who are deciding betwe
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910866
Entities
People
- Robert R Flavell
Organizations
- United States Army
- University of California, San Francisco