USPIO MRI in protate cancer: Vascular imaging and lymph node staging
The aim of the project is to investigate the diagnostic accuracy of simultaneous 18F-FACBC PET and iron nanoparticle (USPIO) enhanced MRI for detection of lymph node metastases in prostate cancer patients.Patients with advanced prostate cancer often present with spread of the cancer to the lymph nodes. It is important to identify patients with malignant lymph nodes, because knowing the extent of the cancer helps to choose the best treatment option, thereby reducing potential side effects. The aim of the project is to improve the sensitivity and specificity of the detection of malignant lymph nodes in prostate cancer patients using a combination of MRI using iron oxide nanoparticles (USPIOs) as contrast agent and 18F-FACBC-PET. The project is at the planning stage and no patients have been recruited to the study yet. The project has been extended until the end of 2018 due to and increase of the costs for the USPIO contrast agent purchase. USPIO contrast agents are currently not clinically available. The commercial venture SPL Medical in Nijmegen, Netherlands, is re-introducing the USPIO Combidex® (ferumoxtran-10) to the market. We are in contact with the company to discuss the purchase of the contrast agent. Currently, the company is only producing Combidex® for research purposes and has not yet started large scale productions. This means that we can only buy a whole production batch and have to upscale our project. This results in higher costs, and our available funds are not sufficient to purchase the contrast agent and start the project. We have applied for additional funding from other sources and can start the study once we have sufficient funding to purchase a batch of Combidex®.
This project is an addition to a Post-Doc project, funded by Helse-Midt Norge. The project aims to improve diagnostic imaging in prostate cancer. Prostate cancer patients are a heterogeneous population and it is essential to perform an individual assessment of the aggressiveness and spread of the cancer to select an optimal treatment strategy.One challenge in prostate cancer is the detection of lymph node metastases. We are currently in the process of planning a clinical feasibility study to investigate whether a combination of positron emission tomography (PET) and magnetic resonance imaging (MRI) with iron oxide contrast agents can improve the detection metastatic lymph nodes. PET contrast agents have been shown to accumulate both in primary prostate cancer and in metastatic lymph nodes, making PET a promising tool to aid lymph node characterization. Ultrasmall superparamagnetic iron oxide (USPIO) contrast agents have also shown great potential in the detection of metastatic lymph nodes. These contrast agents are taken up by immune cells (macrophages), which are highly concentrated in healthy lymph nodes but not in cancerous nodes. In this study, we will investigate if PET and USPIO-MRI can improve current procedures for lymph node detection. This will improve patient care, because extensive removal of lymph nodes may be avoided, which would reduce side effects caused by prostate cancer treatment. Currently, we are obtaining approval from the regional committee for medical and health research ethics for this clinical study. The FFU funding will be used for this clinical part of the project. In addition to the lymph node staging study, we want to improve characterization of the primary prostate cancer. In mouse models of prostate cancer, we will investigate if MRI with USPIOs can be used to help characterize prostate cancer. We will test if this method could replace dynamic contrast-enhanced (DCE)-MRI with gadolinium based contrast agents, which is part of the standard multiparametric MRI examination of prostate cancer patients. If MRI with USPIOs shows good results for primary prostate cancer characterization, it would be possible to combine it with lymph node imaging, which would require only a single contrast agent dose. For this preclinical study we have obtained preliminary results. We have used mice that spontaneously develop prostate cancer and used MRI to monitor the development of the cancer. We used the same imaging protocol that is currently recommended for prostate cancer patients: T2w imaging, diffusion-weighted imaging and dynamic contrast-enhanced imaging with a clinical gadolinium-based contrast agent. In addition, we performed USPIO-MRI. After MRI, we confirmed the location of cancerous prostate regions with histology. Preliminary results indicate that the clinical MRI protocol is also useful to detect prostate cancer in mice. Iron-oxide based imaging seemed to be less helpful in detecting cancer, but further analysis has to be performed to show conclusive results. An abstract based on these preliminary preclinical results was sent to the International Society for Magnetic Resonance in Medicine to be considered for presentation at the annual conference in 2017.