{"id":86,"date":"2017-03-17T14:50:33","date_gmt":"2017-03-17T18:50:33","guid":{"rendered":"http:\/\/sites.williams.edu\/cec5\/?page_id=86"},"modified":"2017-04-14T23:04:23","modified_gmt":"2017-04-15T03:04:23","slug":"technetium-complexes-for-medical-diagnostics","status":"publish","type":"page","link":"https:\/\/sites.williams.edu\/bigchem\/topics\/metals-in-medicine\/technetium-complexes-for-medical-diagnostics\/","title":{"rendered":"Technetium Complexes for Medical Diagnostics"},"content":{"rendered":"

Summary<\/h1>\n

The radioactive properties of\u00a099m<\/sup>Tc, such as its\u00a0short half life, low toxicity, and emission energy make it an ideal element for radioimaging.99m<\/sup>Tc radioimaging could be a promising diagonstic tool for diseases such as Alzheimer’s, that require a non-invasive method of diagnosis.\u00a0By complexing\u00a099m<\/sup>Tc with targeting ligands, the compound can be made specific for\u00a0Alzheimer’s disease, and hopefully lead to a radiodiagnostic tool.\u00a0<\/span><\/p>\n

Table of Contents<\/b><\/h1>\n

Radiodiagnostics<\/a>
\nTechnetium: Properties and Coordination<\/a><\/span>
\nCase Study: SPECT Imaging for Alzheimer\u2019s<\/a><\/span>
\n<\/a><\/p>\n

Radiodiagnostics<\/h1>\n

Radiodiagnostics are a powerful way to noninvasively look inside a patient\u2019s body. They rely on imaging agents that contain a radioactive nuclide, such as 18<\/sup>F (in fluorodeoxyglucose, which is used for positron emission tomography (PET) scans), or 99m<\/sup>Tc, used in SPECT imaging. The radiolabeled imaging agent localizes to a specific part of the body, where it emits radiation that can be measured by an external instrument. Typically, radiopharmaceuticals used for imaging emit either gamma rays or positrons (while radiopharmaceuticals used for therapy emit particles such as \u03b1 or \u03b2<\/span>– <\/span>particles) (Alberto).\u00a0<\/span><\/p>\n

There are two main types of radioimaging: PET (positron emission tomography) and SPECT (single photon emission computed tomography). PET reads the emission of positrons, while SPECT reads the emission of gamma rays. PET scans are higher in resolution and sensitivity. SPECT, on the other hand, relies on longer-lived radioisotopes and has lower direct costs. SPECT imaging has a variety of uses: numerous cardiac, bone, lung, kidney, liver, and gall bladder SPECT scans are performed every year. Both PET and SPECT can be combined with CT scans to give more precise positional information (Jaffer).<\/span><\/p>\n

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Figure 1.<\/strong> Diagram of SPECT imaging of the brain<\/span><\/p>\n

SPECT works by converting gamma rays into electrical signals that can be read by a computer. The basic components of the instrument (shown in Figure 1<\/span>) are as follows: gamma rays exit the body and encounter a collimator, usually made of lead, which improves the resolution of the imaging. The lead blocks the progress of rays traveling at an oblique angle, while small holes let through rays traveling in the correct direction. The rays then interact with scintillation crystals, such as NaI, which luminesce when excited by gamma rays. The luminescence then hits the photomultiplier tubes (PMTs), which amplify the signal and convert it to an electrical charge, which is sent to the computer. This process is performed from many angles around the body, allowing the computer to create a 3D reconstruction.<\/span><\/p>\n

Some important considerations for choosing an appropriate radionuclide for imaging include radiation emission energy, half life, and stability of the daughter nuclide. The radiation must penetrate the body so that it can be measured by an external instrument, and the ideal range is between 100keV and 200 keV. Furthermore, the ideal radionuclide has a short enough short half-life. However, the half-life has to be long enough so that the radiopharmaceutical can be synthesized, injected into the patient, and used for imaging (a process lasting about the duration of an afternoon). Upon decay, the radionuclide must have a stable daughter nuclide so that there is no further radiation exposure for the patient (Alberto).<\/span><\/p>\n

<\/a>Technetium: Properties and Coordination<\/b><\/h1>\n

99m<\/sup>Tc, a metastable isotope of technetium,<\/span> is a good fit for radioimaging. 99m<\/sup>Tc\u00a0<\/span>decays to 99<\/sup>Tc<\/span>, releasing gamma photons (Equation 1) with an energy of 140 keV and a half-life of six hours. Furthermore, the daughter nuclide 99<\/sup>Tc<\/span> is very stable, with a half-life of 212,000 years, and has low toxicity (Bartholoma).<\/span><\/p>\n

99m<\/sup><\/span>Tc \u2192 <\/span>99<\/sup><\/span>Tc + \u03b3<\/span>\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0\u00a0\u00a0\u00a0\u00a0 (Equation 1)<\/span><\/p>\n

In addition, 99m<\/sup>Tc<\/span>\u00a0is readily available through a generator system: immobile 99<\/sup><\/span>Mo loaded onto an aluminum oxide column will decay to 99m<\/sup>Tc\u00a0<\/span>through <\/span>\u03b2<\/span>– <\/span>and \u03b3 emission (Figure 2). The daughter nuclide has a lower affinity for the column and can be continuously eluted in the form of [99m<\/sup>TcO4<\/sub><\/span>]–<\/sup>\u00a0while 99<\/sup>Mo<\/span>\u00a0remains bound to the column. The generator system makes 99m<\/sup>Tc\u00a0<\/span>readily available and cost effective (Bartholoma).<\/span><\/p>\n

<\/p>\n

Figure 2.<\/strong> 99m<\/sup><\/span>Tc is formed from <\/span>98<\/sup><\/span>Mo (Bartholoma).<\/a><\/span><\/p>\n

Located in Group 7, Tc is a second row transition element that has many oxidation states, from Tc(I) to Tc(VII). The most common oxidation states are VII (the oxidation state of technetium in [99m<\/sup>TcO4<\/sub>]–<\/sup><\/span>), V, III, and I. Oxidation states V and I are most often used in imaging.<\/span><\/p>\n

Due to its variety of oxidation states, Tc can bind a large variety of ligands. Higher oxidation states are harder acids, and therefore bind hard bases. The high charge of the higher oxidation states can be stabilized by \u03c0-donor ligands (such as O2-<\/sup><\/span>), while the lower oxidation states have higher electron density, which can be stabilized through backbonding with \u03c0-acceptor ligands (such as CO) (Alberto).<\/span><\/p>\n

The oxidation states have different coordination geometries: Tc(I) complexes are octahedral; Tc(III) often has distorted octahedral complexes but can expand its coordination number to seven; and Tc(V) complexes are often square pyramidal. Most Tc(V) compounds contain either the [Tc=O]<\/span>3+\u00a0<\/sup>or [Tc\u2261N]2+<\/sup><\/span>\u00a0core, since O2-<\/sup><\/span>\u00a0and N3-<\/sup><\/span>\u00a0are \u03c0-donors and stabilize its high oxidation state. As a \u03c0-donor ligand, O2-<\/sup><\/span>\u00a0exerts a strong trans influence, weakening the strength of the trans bond such that most complexes containing the[Tc=O]3+<\/sup><\/span>\u00a0core have a coordination number of five with a square pyramidal geometry (Alberto).<\/span>
\n<\/a><\/p>\n

Case Study: SPECT Imaging for Alzheimer\u2019s Disease<\/b><\/h1>\n

Alzheimer\u2019s disease (AD) is a serious neurodegenerative disease, and it is the most prevalent form of dementia, affecting more than five million Americans. However, it is very hard to diagnose definitively, and currently, the only way to definitively diagnose AD is post mortem. Radioimaging provides a potential solution to the need for effective, noninvasive ways to diagnose AD while the patient is still alive (Zhang). For a brief introduction for Alzheimer’s disease, see the video below.\u00a0<\/span><\/p>\n