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| Fig. 1: Trapping of radiolabels in the cell for imaging. 18FDG used in PET is shown along with 111In for SPECT. (Source: Wikimedia Commons ) |
Nuclear medicine is a field that includes imaging for diagnostics and therapy. The nuclear aspect comes from the use of radiolabels to either obtain a signal for imaging or to combat cancer through the energy release of the radiolabels. Two main imaging techniques exist for use with radiolabels: positron emission tomography (PET) and single photon emission computed tomography (SPECT). [1] Each of these technologies has benefits in determining detection of cancer or abnormalities in the body, but the use of multiple radiolabels is possible in SPECT which allows detection of multiple objects or diseases in the body. Both PET and SPCET rely on gamma-rays which are detected by scintillator crystals, whose quality dictates the resolution of the image. [2] In this report the focus will be on the radiolabels used in these technologies for imaging and also as therapeutics.
Radiolabels can be distinguished by their half lives and their amount of energy release, and their type of emission. The measure of the radiolabel's nuclear activity, measured in curie (Ci) is 3.7 × 1010 disintegrations per second; the alternative unit is the Becquerel (Bq) which corresponds to one disintegration per second. [1] A half-life determines the decay characteristics of the radiolabel. The decay profile follows an Arrhenius relation
where A0 is the initial activity at time zero and Tp is the physical half life. [2] The other measure of half life is a biological half life, which refers to the time for half of the administered radiolabel to be cleared from the body. Physical and biological half life are combined to give an effective half life
| Te | = | Tp Tb
Tp+Tb |
where Tb is the biological half life and Te is the effective half life. [1] Half life is an important characteristic of the radiolabel since a physical and effective half time greater than the time required to prepare the injection is needed to obtain a proper measurement.
Another figure of merit is the amount of energy release from the radiolabel. The amount of energy release comes from the type of decay that they undergo. As mentioned, for PET and SPECT gamma-ray photons are required for detection, therefore the radiolabels must either undergo decay by gamma-ray emission or positron emission followed by annihilation with an electron, resulting in a gamma-ray photon. [1] The decay needs to conserve energy, momentum, and electrical charge after the annihilation and therefore which results in two gamma-rays with 511 keV traveling in opposite direction. [2] For proper detection of the gamma-rays energy of 50-500 keV is required. [1] Apart from the energy and half-life considerations, toxicity needs to be accounted for. Any type of prolonged exposure to the radiation should also be minimized.
Two main ways for the production of medical radiolabels exist: from a generator system or cyclotron. Both of these require a radioactive nucleotide, typically produced in a nuclear reactor by fission reactions. [2] These fission reactions can produce 99Mo which can be used in generator systems. [3] The most common generator system is 99Mo-99mTc, where the parent isotope (Mo) decays to the daughter isotope which has a smaller half-life and therefore provides less exposure of radiation to the patient. The generator system produces short lived isotopes that only emit gamma rays. [1] In the cyclotron nuclear reactions take place by bombardment of charged particles to target elements, where typically neutrons are emitted resulting in a neutron deficient atom. This neutron deficient atom results in positron emission followed by gamma ray emission. [1] Either of these systems (generator or cyclotron) need to be present at a nuclear imaging facility due to the rapid decay of the radiolabels used in the body. In the production of these radiolabels quality control for purity is highly regulated. [3]
Approximately 95% of radiolabels used in medicine are used for imaging with few applications to therapeutics in treating cancer patients. [3] Various body parts can be imaged based on the type of radiolabel used. A radiolabel becomes a radiopharmaceutical when it is chemically modified to target specific areas of the body. [3] For example 18F produced by a cyclotron decays with positron emission and is chemically modified to be a part of a precursor of glucose and it is used at 18FDG. [1] This molecules then goes to metabolically active parts of the body, which makes it a good imaging agent for the brain. [3] 99mTc produced by generators is modified to be part of diphosphonate which targets bone and therefore it is a good imaging agent for bone. It can also be modified to be part of other compounds for the targeting of other biological systems such as thyroid, infection, and myocardial perfusion. [1] Fig. 1 shows the trapping of the radiolabel in the cell for signaling in imaging.
Therapy radiopharmaceuticals are used due to their energy release in the site of metastases. The radiation dose is difficult to predict, though the use 131I for the treatment of thyroid cancer or hyperthyroidism is considered safe. [3] Typical radiation doses are 5,000 to 30,000 rad for 131I. Another technique for cancer treatment uses monoclonal antibodies for targeting of the radiolabel to the area of the tumor. This type of technique lacks specificity and healthy tissue suffers from unnecessary exposure to radiation. This is also a true concern with any of the therapeutic uses of radiolabels.
Radiolabels have great use in imaging techniques for PET and SPET technologies. Their half life make it so that an cyclotron or nuclear generator exist within a close distance to the nuclear imaging facility. Since there are many options for radiolabels and they can be chemically modified to be part of many molecules in the body, they can serve to target different body parts and therefore image different parts of interest.
© Gabriela Bernal. The author grants permission to copy, distribute and display this work in unaltered form, with attribution to the author, for noncommercial purposes only. All other rights, including commercial rights, are reserved to the author.
[1] F. A. Mettler and M. J. Guiberteau, Essentials of Nuclear Medicine Imaging, 6th Ed. (Saunders, (2012).
[2] E. E. Kim et al., Handbook of Nuclear Medicine and Molecular Imaging- Principles and Clinical Applications (World, 2012).
[3] G. B. Saha, Fundamentals of Nuclear Pharmacy, 6th Ed. (Springer, 2009).
