Molecular imaging and related novel technologies

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.

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

• 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

• 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)

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

• 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)

• Identify: Apoptosis/macrophages/intraplaque hemorrhage
• Target: Annexin
• Mechanism: Radioisotope decay

• Identify: Sites of inflammation
• Target: Lymphocytes
• Mechanism: Radioisotope decay

• Identify: Thrombosis
• Target: Platelet glycoprotein IIb/IIIa receptor
• Mechanism: Radioisotope decay

• Identify: Angiogenesis
• Target: Integrin α_Vβ₃
• Mechanism: Radioisotope decay

• Target: Stem cells
• Mechanism: Radioisotope decay

• Receptor targeting of specific cells/proteins
• High molecular weight to limit extracellular diffusion
• Albumin-bound to remain intraluminal
• Lipophilic agents (gadofluorine)

• 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

• Identify: Angiogenesis
• Target: Integrin α_Vβ₃

• Identify: Thrombosis
• Target: Fibrin

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

• USPIOs
• ¹⁸FDG
• ^99mTc-annexin
• ^99mTc-interleukin-2
• Prosense
• Paramagnetic nanoparticles

• ^99mTc-apcitide
• EP-2104R

• ^99mTc-NC100692
• ¹¹¹indium-oxine
• Magnetized nanoparticles (MNP)

• Academy of Molecular Imaging.

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