In Vivo Imaging of Rat Vascularity with FDG-Labeled Erythrocytes

Abstract

Microvascular disease is frequently found in major pathologies affecting vital organs, such as the brain, heart, and kidneys. While imaging modalities, such as ultrasound, computed tomography, single photon emission computed tomography, and magnetic resonance imaging, are widely used to visualize vascular abnormalities, the ability to non-invasively assess an organ’s total vasculature, including microvasculature, is often limited or cumbersome. Previously, we have demonstrated proof of concept that non-invasive imaging of the total mouse vasculature can be achieved with 18F-fluorodeoxyglucose (18F-FDG)-labeled human erythrocytes and positron emission tomography/computerized tomography (PET/CT). In this work, we demonstrate that changes in the total vascular volume of the brain and left ventricular myocardium of normal rats can be seen after pharmacological vasodilation using 18F-FDG-labeled rat red blood cells (FDG RBCs) and microPET/CT imaging. FDG RBC PET imaging was also used to approximate the location of myocardial injury in a surgical myocardial infarction rat model. Finally, we show that FDG RBC PET imaging can detect relative differences in the degree of drug-induced intra-myocardial vasodilation between diabetic rats and normal controls. This FDG-labeled RBC PET imaging technique may thus be useful for assessing microvascular disease pathologies and characterizing pharmacological responses in the vascular bed of interest.

Design of erythrocyte-derived carriers for bioimaging applications

“…To date, the imaging function of ECs has been documented in diagnosing and monitoring various physiological conditions that involve abnormalities or alterations in the vasculature, for example, myocardial changes in response to injury and drug action. FDG-labelled erythrocytes combined with PET/CT were used to detect differences in the degree of druginduced intramyocardial vasodilation between diabetic rats and normal controls [59], and to locate the area of myocar-dial injury in a surgical myocardial infarction rat model [59].…”

Red Blood Cells as Drug Delivery and Imaging Agents: An Update

“…Matsusaka et al showed that heat-damaged red blood cells labeled with FDG could be used to image the splenic tissue in a rat model with PET [56]. Wang et al showed that FDG labeled red blood cells could be used to indirectly detect changes in myocardial and cerebrovascular perfusion in normal rats with PET imaging after exposure to pharmacologic vasodilators [57]. In addition, Wang showed that changes in myocardial perfusion in rat models of myocardial infarction and diabetic cardiomyopathy could also be detected by PET imaging with FDG-labeled red blood cells.…”

Special Issue “In Vivo Nuclear Molecular Imaging in Drug Development and Pharmacological Research”

“…The results correlate with metabolic 18 F-FDG positron emission tomography (PET) imaging and were further validated by tissue staining. Furthermore, 18 F-FDG RBC PET can map drug-induced intra-myocardial vasodilation in diabetic rats and normal controls [ 10 ]. This technique is operationally simple and may be promising in the non-invasive detection of whole-body microvascular pathologies and evaluation of treatment response with therapeutics targeting microvascular diseases.…”