Health Dictionary
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Molecular imaging and related novel technologies
Introduction
Editors-in-Chief: Eric A. Osborn, M.D., Ph.D. [1] and Eli V. Gelfand, M.D. [2] (Beth Israel Deaconess Medical Center, Harvard Medical School)
Introduction
Introduction
Molecular imaging utilizes specialized probes and non-invasive imaging techniques to identify biological processes in vivo by targeting specific molecules or cell types. Probes are being developed to detect a wide range of cardiovascular disease states including atherosclerosis, thrombosis, and myocardial infarction. Advancements in molecular biology, chemistry, bioengineering, and nanotechnology are stimulating a rapid growth in molecular imaging research and clinical trials.
Requirements
Requirements
- Imaging system with detectors able to localize the desired probe
- High-affinity ligand that recognizes the intended molecular or cellular target
General principles
General principles
Ideal ligand properties
- High sensitivity and specificity for the target
- Kinetics that allow rapid detection
- Utilize amplification strategies to boost the signal
- Ability to be easily conjugated to signal detection compounds and maintains functionality
- Biocompatible and non-toxic
Choice of ligand
- Pro:
- Involved in processes with a strong clinical or biological interest
- Molecules with signal amplification potential (internalizing receptors, enzymes, multivalency)
- Small size (antibody fragments, peptides, carbohydrates, nanoparticles)
- Con:
- Inaccessible molecules
- Low-abundance (DNA, RNA, poorly expressed proteins)
Imaging modalities
Imaging modalities
- Nuclear
- Positron emission tomography (PET)
- Single-photon emission computed tomography (SPECT)
- Magnetic resonance imaging (MRI)
- Optical
- Near-infrared fluorescence (NIRF)
- Fluorescence-mediated tomography
- Ultrasound
Probes
Probes
PET
18FDG
- Identify: Sites of glucose metabolism
- Target molecule: Glucose transporter-1, hexokinase
- Target cell: Predominately macrophages (atherosclerotic lesions)
- Mechanism: Radioisotope decay (positron emitter, t½ 110 minutes)
SPECT
99mTc-annexin
- Identify: Apoptosis/macrophages/intraplaque hemorrhage
- Target: Annexin
- Mechanism: Radioisotope decay
99mTc-interleukin-2
- Identify: Sites of inflammation
- Target: Lymphocytes
- Mechanism: Radioisotope decay
99mTc-apcitide
- Identify: Thrombosis
- Target: Platelet glycoprotein IIb/IIIa receptor
- Mechanism: Radioisotope decay
99mTc-NC100692
- Identify: Angiogenesis
- Target: Integrin αVβ3
- Mechanism: Radioisotope decay
111indium-oxine
- Target: Stem cells
- Mechanism: Radioisotope decay
MRI
Gadolinium-based
- Receptor targeting of specific cells/proteins
- High molecular weight to limit extracellular diffusion
- Albumin-bound to remain intraluminal
- Lipophilic agents (gadofluorine)
Ultrasmall particles of superparamagnetic iron oxide (USPIOs)
- Identify: Sites of inflammation
- Target: Macrophages (also some interaction with smooth muscle and endothelial cells)
- Mechanism: Induce signal reductions via susceptibility effects on T2- and T2*-weighted images
- Characteristics: 3 nm size
Paramagnetic nanoparticles
- Identify: Angiogenesis
- Target: Integrin αVβ3
EP-2104R
- Identify: Thrombosis
- Target: Fibrin
NIRF
Prosense
- Identify: Sites of inflammation
- Target: Cysteine protease activity
- Mechanism: Fluorescence activated by substrate cleavage
Clinical applications
Clinical applications
Atherosclerosis
- USPIOs
- 18FDG
- 99mTc-annexin
- 99mTc-interleukin-2
- Prosense
- Paramagnetic nanoparticles
Thrombosis
- 99mTc-apcitide
- EP-2104R
Myocardial infarction
- 99mTc-NC100692
- 111indium-oxine
- Magnetized nanoparticles (MNP)