Molecular imaging and related novel technologies

# 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)
- 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)
- Inaccessible molecules
- Low-abundance (DNA, RNA, poorly expressed proteins)

# Imaging modalities
- Nuclear
Positron emission tomography (PET)
Single-photon emission computed tomography (SPECT)
- Positron emission tomography (PET)
- Single-photon emission computed tomography (SPECT)
- Magnetic resonance imaging (MRI)
- Optical
Near-infrared fluorescence (NIRF)
Fluorescence-mediated tomography
- 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, t12 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 V3
- 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 T2weighted images
- Characteristics: 3 nm size

### Paramagnetic nanoparticles
- Identify: Angiogenesis
- Target: Integrin V3

### 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.