Etienne Croteau

Cardiac Metabolism Imaging and Chemotherapy Cardiotoxicity

Cardiac oncology is a field that will become increasingly important in clinical practice as we become more effective in treating cancer and those treated with chemotherapy live longer. Potential cardiac toxicity associated with some chemotherapy treatments can cause significant morbidity. Molecular positron emission tomography (PET) to assess cardiac metabolism is a promising technology that could increase our knowledge of chemotherapy-related toxicity in the heart. We review the utility of PET cardiac imaging to evaluate the toxic effects of chemotherapy on metabolism. Free fatty acids, glucose and ketone bodies are major substrates for cardiac energy consumption, and adaptations to their use can occur under differing conditions. Cardiovascular complications of chemotherapy can include direct effects on metabolism as well as injury to myocardial tissue by effects on endothelial function, hypertension or ischemia. Even novel chemotherapies that are designed to be more specific in their actions continue to be associated with cardiotoxicity. Further study is required to understand the effects of cardiotoxicity related to chemotherapy, and to develop techniques for its detection as well as prevention. PET cardiac imaging could be used to assist in the early detection of cardiotoxicity and help guide management clinically. It may offer insights to assist in the development of novel treatments and methods for cardioprotection.

Treatment with enalapril and not diltiazem ameliorated progression of chronic kidney disease in rats, and normalized renal AT1 receptor expression as measured with PET imaging

ACE inhibitors are considered first line of treatment in patients with many forms of chronic kidney disease (CKD). Other antihypertensives such as calcium channel blockers achieve similar therapeutic effectiveness in attenuating hypertension-related renal damage progression. Our objective was to explore the value of positron emission tomography (PET) imaging of renal AT1 receptor (AT1R) to guide therapy in the 5/6 subtotal-nephrectomy (Nx) rat model of CKD. Ten weeks after Nx, Sprague-Dawley rats were administered 10mg/kg/d enalapril (NxE), 30mg/kg/d diltiazem (NxD) or left untreated (Nx) for an additional 8–10 weeks. Kidney AT1R expression was assessed using in vivo [18F]fluoropyridine-losartan PET and in vitro autoradiography. Compared to shams, Nx rats exhibited higher systolic blood pressure that was reduced by both enalapril and diltiazem. At 18–20 weeks, plasma creatinine and albuminuria were significantly increased in Nx, reduced to sham levels in NxE, but enhanced in NxD rats. Enalapril treatment decreased kidney angiotensin II whereas diltiazem induced significant elevations in plasma and kidney levels. Reduced PET renal AT1R levels in Nx were normalized by enalapril but not diltiazem, and results were supported by autoradiography. Reduction of renal blood flow in Nx was restored by enalapril, while no difference was observed in myocardial blood flow amongst groups. Enhanced left ventricle mass in Nx was not reversed by enalapril but was augmented with diltiazem. Stroke volume was diminished in untreated Nx compared to shams and restored with both therapies. [18F]Fluoropyridine-Losartan PET allowed in vivo quantification of kidney AT1R changes associated with progression of CKD and with various pharmacotherapies.

Cardiac Micro-PET-CT

Molecular imaging is a rapidly emerging field, with the use of multi-modality or hybrid technology scanners for in vivo investigations covering a broad spectrum of disease. Cardiac micro-PET-CT is one such promising multimodality. Standalone imaging technologies such as PET and CT have existed for several decades, however, they have only recently been utilized in concert, mainly for clinical cancer imaging. Cardiovascular events are responsible for nearly one-third of deaths in North America every year. Atherosclerosis, coronary artery disease (CAD), and heart failure are the most common types of heart disease. Cardiac imaging-related research into their prevention and treatment has contributed to a decrease in mortality. This review outlines the recent progress in the development and application of advanced cardiac micro-PET-CT technology. Current development of novel PET radiotracers focusing on diagnosis and characterization of different stages of atherosclerosis is discussed, as well as myocardial perfusion radiotracers mimicking previously established SPECT tracers and others. Small animal (mouse and rat) models of disease investigated with cardiac imaging are becoming more common, and will facilitate rapid translation to clinical studies with improvement in micro-PET-CT technology. Also, increasingly popular animal models for cardiovascular disease research such as mini-pigs and rabbits are used with interventional therapies, including catheterization due to larger artery sizes. The emergence of cardiac CT will be discussed with comparison between preclinical and clinical approaches, including consideration of radiation doses.