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Molecular imaging is the visualization, characterization, and measurement of biologic processes at the molecular and cellular levels in humans and other living systems. It is essentially a noninvasive means to study in vivo biochemistry and cell biology and is useful to optimize diagnosis and therapy of disease in individualized patients. Nuclear medicine techniques and optical imaging techniques are most commonly used to perform molecular imaging, the former predominantly in humans and the latter predominantly in small animals for preclinical research.
A radioactive compound (i.e., a radiotracer) that targets a molecular process, cellular process, or disease of interest is administered to a patient. Photons are emitted from the radiotracer in the patient, and an imaging detector is used to detect the distribution of the radiotracer. Images are then created by a computer system. The main nuclear medicine imaging techniques include planar scintigraphy, single photon emission computed tomography (SPECT), and positron emission tomography (PET). Nuclear medicine techniques are used not only for diagnostic purposes, but also less commonly to treat cancer, in which case the radiotracers used accumulate in tumor sites and also emit charged particles that promote cancer cell death.
Molecular imaging allows for the noninvasive functional and molecular characterization of normal tissues and disease processes of interest, even when morphologic changes in tissues have not yet occurred. Structural imaging (such as with radiography, computed tomography [CT], magnetic resonance imaging [MRI], and ultrasonography [US]) allows for the noninvasive anatomic assessment of normal tissues and disease conditions based on morphologic and gross functional alterations that occur. Molecular imaging techniques typically have higher contrast resolution (i.e., the ability to distinguish between differences in image intensity) and lower spatial resolution (i.e., the ability to distinguish two adjacent structures as being separate) compared to structural imaging techniques. As such, molecular imaging and structural imaging techniques are complementary.
X-rays and gamma rays are both types of ionizing electromagnetic radiation (i.e., they are photons that are energetic enough to remove electrons from other atoms or molecules) with wavelengths shorter than those of visible light. X-rays are emitted by electrons located outside of the nucleus of an atom, whereas gamma rays are emitted by unstable nuclei within atoms and have higher energies than x-rays. Diagnostic x-ray imaging is referred to as transmission imaging, since images are formed by the transmission of x-ray photons from an external source (outside the patient) through the patient to external detectors. Nuclear medicine imaging is referred to as emission imaging because images are formed by the emission of gamma ray photons from an internal source (inside the patient) through the patient to external detectors.
Radioactivity (i.e., radioactive decay) is the process by which unstable atoms that do not have sufficient binding energy to hold their nuclei together emit ionizing radiation, and it occurs in exponential fashion. Alpha decay occurs when an alpha particle (identical to a helium nucleus) is emitted. Beta decay occurs when a beta particle (such as a positron) is emitted. Gamma decay occurs when a gamma ray is emitted during transition of an atomic nucleus to a lower energy state. Henri Becquerel discovered spontaneous radioactivity from uranium in 1896, and Pierre and Marie Curie discovered radium and polonium in 1898. As a result, all three received the Nobel Prize in Physics in 1903.
Carl Anderson discovered the positron (the “positive electron”) in 1932 and subsequently received the Nobel Prize in Physics in 1936. Positron emission by certain radioisotopes makes PET imaging feasible.
Generators are devices that contain a radioactive parent radioisotope with a relatively long half-life that decays to a short-lived daughter radioisotope, which is then used for diagnostic imaging or therapy. The most commonly used one is the technetium-99m ( 99m Tc) generator, which has molybdenum-99 ( 99 Mo) as the parent radioisotope. As decay of 99 Mo occurs, 99m Tc is formed and can then be eluted for use with various molecules to obtain scans of different physiologic processes. Cyclotrons are circular devices in which charged particles are accelerated and deflected into a target to create radioisotopes such as carbon-11 ( 11 C) and fluorine-18 ( 18 F). Medical grade nuclear reactors are sometimes used to create other isotopes.
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