The Smarter Imaging Program includes a mix of projects that are relatively advanced and those that are at an earlier stage.
Smarter Imaging of Breast Cancer
Currently, the most widely used tool for detection of breast cancer is screening mammography. Mammography has demonstrated contribution to an approximately 30 per cent reduction in breast cancer mortality for women screened between the ages of 40 and 74. Typically, mammography has a sensitivity of over 80 per cent and a specificity between 86 per cent and 96 per cent. However, for women with dense breasts the sensitivity can be as low as 60 per cent and for young, high risk women (e.g., BRCA mutation carriers) it call fall as low as 40 per cent. Digital mammography provides improved sensitivity in the dense breast, but for the high-risk population, a combination of contrast-enhanced breast MRI and mammography is recommended as it can boost sensitivity to about 90 per cent, but specificity can be lower than desirable. While some consideration is being given to development of more sensitive screening methods, such as an MRI technique that could be used without an injected contrast agent or radionuclide approaches, the ideal screening method is probably one that would make use of a circulating tumour marker (yet to be identified). One of the sub-projects in SIP addresses opportunities to improve the specificity of breast cancer detection with MRI by designing specialized computer-assisted detection tools.
More immediate benefits would come at the diagnostic stage by being able to distinguish cancers destined to progress and become lethal from those that were not. Such prognostic markers would be of great benefit in helping to reduce overtreatment of a disease, a problem that is known to exist. Currently, without such markers, treatment tends to be “one size fits all” and in many cases is likely delivered less effectively and certainly less efficiently than optimal.
In one of the SIP sub-projects, we attempt to use vascular and morphological features of ductal carcinoma in-situ to differentiate between aggressive and more indolent cancers and use radiolabeleld targeted probes to interrogate the HER2 receptor to assess response to Herceptin.
The Prostate Cancer Project
Unlike as in breast cancer, currently we do not have imaging screening techniques of equivalent sensitivity and specificity for prostate cancer, although the PSA test can achieve high sensitivity (95 per cent), but at very low specificity (20 per cent). However, it is known that not all prostate cancers will become lethal and that some can safely remain untreated. But again, as in breast cancer, it is not known which cancers are of this type.
The major roles for imaging in prostate cancer are in detection, characterizing the aggressiveness of disease to select patients for treatment or watchful waiting, and in guidance of therapy. In the initial phase of this project, a hybrid optic/radionuclide PSMA probe will be developed for detection and biopsy guidance. In addition, several candidate approaches will be refined for the purposes of more accurately defining the extent of disease and characterizing prostate cancers. These include hyperpolarized 13C MRI, MRI to quantify changes in sodium concentration, and FCH PET imaging of tumour proliferation. The most promising of these ideas will be supported through further validation and, ultimately, application.
Smarter Imaging of the Body
In the Smarter Imaging of the Body Project (cancers of the liver and pancreas), we will address specific challenges associated with cancers in these sites. Pancreatic cancer has been a daunting problem because the disease typically surfaces clinically when it is at an advanced state. We currently have no reliable technique for early detection, although there is some evidence that MRI could be helpful. In an attempt to make some inroads on this problem, we propose to improve the image quality of MRI for screening high-risk individuals. Liver metastases are a common ultimate cause of death from cancer, and hepatocellular carcinoma is an increasing problem internationally. We will improve ultrasound imaging techniques for the guidance of ablative therapy for primary or metastatic liver tumours. We will also explore the use of an ultrasound system for earlier detection of HCC based on nanodroplets targeted to the surface protein, Glypican3.
Novel Imaging Probes Project
The Novel Imaging Probes Project is focused on development of new imaging tracers and technologies for specific cancer sites and, should they be successful, can be applied clinically in a fairly short time frame. OICR also has a mandate to explore potentially high-impact ideas at an earlier (and therefore, riskier) stage of development. Some of these are specific to a single cancer site or modality, while others might provide platforms with wider applicability.
In this project three sub-projects focus on determination of tumour aggressiveness. One employs a new MRI imaging method together with commercially available molecular probes to characterize breast cancers, while the second exploits overexpression of urokinase plasminogen activator and targeted SPECT or PET probes to identify aggressive breast or pancreatic tumours. The third extends previous OICR probe activity to use porphysomes as contrast agents for PET imaging to characterize prostate cancers and eventually as a potential platform for targeted treatment.
Probes can also be used to evaluate tumour responsiveness to therapy. One sub-project assesses intracellular pH though a MR phenomenon referred to as chemical exchange saturation transfer (CEST) and extracellular pH through a paramagnetic CEST technique to evaluate lung tumours with work carried out in a mouse model. Another uses MRI to track the delivery of vaccine-carrying dendritic cells to lymph nodes, potentially for the immunotherapy of prostate cancer.