Molecular imaging and related novel technologies

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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

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

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

• 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

PET

¹⁸FDG

• Identify: Sites of glucose metabolism
• Target molecule: Glucose transporter-1, hexokinase
• Target cell: Predominately macrophages (atherosclerotic lesions)
• Mechanism: Radioisotope decay (positron emitter, t_½ 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 α_Vβ₃
• 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 α_Vβ₃

EP-2104R

• Identify: Thrombosis
• Target: Fibrin

NIRF

Prosense

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

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)

Further online resources

• Academy of Molecular Imaging.

References

<biblio> #ref1 pmid=17724271 </biblio>