Techniques for Molecular Imaging

Project Leader

Zhonglin Liu, M.D.

Project Summary

The overall objective of Core Project V is to translate the advances in biomedical imaging developed in the other Core Projects into specific investigations of important biomedical topics. To do so, we will apply SPECT imaging techniques in small-animal models for basic investigations in cardiology, oncology, and neurology. Investigations will emphasize quantitative dynamic imaging. These methods will serve as a test bed for the other Core Projects, and they will also provide a platform for collaborative research and ultimately for clinical translation.

Current Projects

Implement and validate small-animal models of ischemia-reperfusion injury and use selected radiotracers to detect and quantify the injury and its development.

• Myocardial perfusion imaging in rat/mouse heart models.

• Detection of myocardial necrosis and apoptosis in rat hearts with ischemia-reperfusion injury.

• Inflammation imaging in rat hearts with ischemia-reperfusion injury.

Determine the effects of cardioprotective strategies using the imaging methods and small-animal models.

• Imaging study of protective role of ischemic preconditioning in rat hearts with ischemia-reperfusion.

• Investigation of the short-term and long-term cardioprotective effects of melatonin (N-acetyl-5-methoxytryptamine) in ischemia-reperfused rat hearts with using noninvasive SPECT imaging.

• Assessment of the cardioprotective effects of different anesthetic agents using rat heart models and SPECT imaging.

• In vivo tracking of transplanted rat Mesenchymal Stem Cells (MSCs) by SPECT imaging.

Explore the tumor-targeting properties of novel-imaging agents in animal models of human cancer and characterize the properties of these agents for evaluating tumor response to chemotherapy.

• ^99mTc-glucarate imaging of xenografted human breast cancer and lung cancer.

• Tumor targeting using ^99mTc-labeled vasoactive intestinal peptide (VIP).

• Investigation of tumor glucose metabolism using ^99mTc-ethylenedicysteineglucosamine (ECDG).

• Characterization of radiolabeled bi-specific ligands targeting tumor growth factors.

• Evaluation of tumor response to chemotherapy using radiolabeled biomarkers for apoptosis.

Click here for an overview of some animal imaging research.

Animal Imaging Studies at the CGRI

Successive 1 mm coronal slices of FastSPECT II images of apoptosis in the infarcted region of a heart.  The tracer was the C2A domain of synaptotagmin  labelled with ^99mTc.  Significant uptake is seen in liver but almost none in normal heart

1 mm sagittal slices of ¹¹¹In –oxine labeled MSCs 48 hrs after intracoronary injection

Illustrations of the dorsal window chamber

Dynamic image sequence showing the positron emission from FDG from an implanted breast tumor in the window chamber.  Exposure time of 2 minutes per image

SPECT imaging of ischemia-reperfused hearts

Left panel: ^99mTc-C2A dynamic images in a rat heart with ischemia-reperfusion. Cardiac blood pool is evident on the 1-min image (top left). A hot spot in the left ventricular wall was achieved 10-30 minutes post-injection. The arrow at 120-min indicates the site of the infarct (bottom right). Right panel: ^99mTc-C2A time-activity curves from infarcted myocardium, viable zone, and lungs.

^99mTc-labeled TNFR2-Fc-IL-1ra images 3 hours post-injection in two ischemic and reperfused rat hearts, showing radioactive “hot spots” in the ischemic area.

^99mTc-TNFR2-Fc-IL-1ra dynamic images. Times in minutes are at lower right of each frame. Uptake is evident in infarcted myocardium and in the liver.

FastSPECT II MIBI images (transverse slices, 1 mm per slice) from a control (left panel) and DOX-treated rat heart (right panel) 2 hours post-injection. Reduced left ventricular wall thickness and inhomogeneous radiotracer distribution were found in the DOX-treated heart.

SPECT imaging of atherosclerosis and vascular restenosis

^99mTc-IL-18bp-Fc-IL-1ra SPECT images of carotid arteries 3 hours post-injection. Increased radioactive uptake was observed in the injured side

Tracking ¹¹¹In-MSCs-GFP after IV injection. Left panel: SPECT images (three transverse slices, 1 mm) show high activity in the lungs at 1 hr post-injection, but not in the heart. Lung activity disappeared 5 days later and activity in the heart (arrow) became detectable. Right panel: Tissue autoradiograph (AR) in selected 10 mm and 10 μm slice shows activity in the ischemic area; microscopic (MS) image shows GFP green light signals (bright white spots on the picture) from where radioactivity accumulated.

Tumor imaging

Tumor chamber and dynamic imaging of HCT116 tumor using ¹⁸F-FDG and  electron imager.

FastSPECT images (coronal slices, 1 mm perslice) show high uptake (dashed mark) of ^99mTc-labeled polypeptide in a peritoneal tumor seeding model with human ovarian cancer.

^99mTc-IL-18bp-Fc-IL-1ra images in HCT116 cancer. Increasing tracer uptake (dashed marks) was shown up to 24 hours post-injection.

Neuro imaging

TTC staining of brain slices from a rat MCAO model (90-minute ischemia followed by 5-hour reperfusion), demonstrating infarctions (TTC-unstained areas) in the left hemisphere.

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