Molecular imaging and related novel technologies

Editors-in-Chief: Eric A. Osborn, M.D., Ph.D. [mailto:eosborn@bidmc.harvard.edu] and Eli V. Gelfand, M.D. [mailto:egelfand@bidmc.harvard.edu] (Beth Israel Deaconess Medical Center, Harvard Medical School)

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

 * Imaging system with detectors able to localize the desired probe
 * High-affinity ligand that recognizes the intended molecular or cellular target

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

 * Nuclear
 * Positron emission tomography (PET)
 * Single-photon emission computed tomography (SPECT)
 * Magnetic resonance imaging (MRI)
 * Optical
 * Near-infrared fluorescence (NIRF)
 * Fluorescence-mediated tomography
 * Ultrasound

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)

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

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

Prosense

 * Identify: Sites of inflammation
 * Target: Cysteine protease activity
 * Mechanism: Fluorescence activated by substrate cleavage

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)

Further online resources

 * Academy of Molecular Imaging.