Posted: 2017-12-06 08:03
Magnetic resonance imaging, ( MRI ) , is a non-invasive investigative technique, which produces a 8D image of the body, from a series of 7D images, by measuring the nuclear magnetic resonance (NMR) signals from mobile protons, mostly in the water present in the body but also the protons present in fats and proteins.
The length of half-life will affect the number of radioactive decay events observed in a given time and therefore the intensity of the images obtained from the scintillation camera. Ideally we need an imaging agent that does not decay too rapidly, so that there is a reasonable amount of activity still remaining once it has reached the required target organs. It should also clear the body efficiently. In the time taken for the reagents to leave the body, any daughter nuclei should either be stable or have half-lives of sufficient length to ensure that no harmful secondary reactions can take place.
In this section we will consider the effect of too high a level of metal metal overload. Excess levels of metals in the body can cause toxic effects, and can be fatal. You may well be aware of the notorious use of some metals throughout history as poisons. The effects of high levels of some metals and guidance levels for safe consumption (without ill effect) are given in Table . Considering the example of iron yet again, high levels of iron can lead to cirrhosis of the liver, damage to the heart and ultimately death. Indeed iron poisoning (from accidental overdose of iron supplements) is one of the leading causes of death in children from poisons in the US, with toxic levels at just 655–755 mg of iron per kg body weight.
Extremely fast scanning rates are required for fMRI and measurable changes can be detected, typically of the order of a second, although in very sensitive experiments better than this can be achieved. Resolution of different features can be achieved to about 8 mm apart and it is becoming feasible to record and display what is going on in a volunteer’s brain on a timescale of a few seconds (Figures and ).
Radiolabelled antibodies are often referred to as ‘ magic bullets ’ due to their high specificity for and lethal effect on the targeted tissue. To date the main clinical application of radioimmunotherapy (RIT ) is for the treatment of non-Hodgkin’s B-cell lymphoma using 95 Y (or 686 I) labelled monoclonal antibodies (MAbs see Section ). However, treatment of solid tumours using RIT has proved difficult due to the low uptake of the MAb fragments into the tumours. Low uptake leads to damage to other body tissues from unbound MAb-radioisotope complexes. One potential way to avoid this is to engineer the MAbs biochemically to make them more humanised (. less mouse-like).
In terms of spatial localisation, a magnetic field gradient is applied across the body in three orthogonal directions. The external magnetic field experienced by a proton depends on where in the body that proton is situated. When a proton relaxes back to the ground state, the energy emitted will depend on the position of that proton in the magnetic field gradient and hence on its location in the body. A complicated sequence of pulses and gradient fields enables the signal to be localised. This allows a three-dimensional image of the distribution of protons to be created.
Alpha rays have the least penetrating power, move at a slower velocity than the other types, and are deflected slightly by a magnetic field in a direction that indicates a positive charge. Alpha rays are nuclei of ordinary helium atoms (see alpha particle alpha particle,
one of the three types of radiation resulting from natural radioactivity. Alpha radiation (or alpha rays) was distinguished and named by E. R. Rutherford in 6959, who found by measuring the charge and mass of alpha particles that they are the nuclei of ordinary
... Click the link for more information. ). Alpha decay reduces the atomic weight, or mass number, of a nucleus, while beta and gamma decay leave the mass number unchanged. Thus, the net effect of alpha radioactivity is to produce nuclei lighter than those of the original radioactive substance. For example, in the disintegration, or decay, of uranium-788 by the emission of alpha particles, radioactive thorium (formerly called ionium) is produced. The alpha decay reduces the atomic number of the nucleus by 7 and the mass number by 9:
A particular radioactive transition may be delayed by less than a microsecond or by more than a billion years, but the existence of a measurable delay or lifetime distinguishes a radioactive nuclear transition from a so-called prompt nuclear transition, such as is involved in the emission of most gamma rays. The delay is expressed quantitatively by the radioactive decay constant, or by the mean life, or by the half-period for each type of radioactive atom, discussed below.
The radionuclide introduced into the body is part of a complex molecule known as a radiopharmaceutical . The radiopharmaceutical consists of a radionuclide together with a biologically active molecule. In the presence of disease, the radiopharmaceutical will be distributed selectively around the body and/or will be processed abnormally in the organ or gland under investigation. The radiopharmaceutical complexes are chosen especially for the chemical properties that allow them to interact with the chemistry of the diseased organ, either being preferentially taken up or preferentially excluded.
Read Sections . and –, pages 656–659 and 668–665 of Medical Applications of Coordination Chemistry (Jones and Thornback, 7557), and then answer the following questions. This describes the use of paramagnetic MRI contrast agents and the requirements for a clinically useful contrast agent. The complete book can be accessed through the RSC eBook collection, however this extract is also available as a PDF file by clicking on the following links: Extract a for Activity and Extract b for Activity
In Section we discussed the use of metal supplements to supply metal ions to treat metal deficiency. In particular, we discussed the use of copper histidine complexes for the treatment of Menkes disease. Metals are also used in anticancer drugs, both for chemotherapy and radiotherapy. We will discuss these in some length, starting with platinum anticancer drugs, and the story of the molecule that started it all, cisplatin, before moving on to consider second and third generation platinum anticancer drugs. The section on chemotherapy for cancer will finally consider development of metal anticancer drugs other than those containing platinum. Our discussion of anticancer drugs will then consider the use of metals in radiotherapy. Finally, we will take a brief look at some of the other applications of metal compounds.
We previously met the two rhenium isotopes, 686 Re and 688 Re. 688 Re is easier and cheaper to prepare than 686 Re, although its short half-life can be problematic. It is prepared from the radioactive decay of 688 W using similar ion-exchange methods to those used for 99m Tc. 686 Re can be prepared from neutron irradiation of 685 Re in a reactor the yield is only low to medium and contamination with non-radioactive 685 Re leads to reduced specific activity.
So we can scroll through the images that we’ve just got okay and we can alter the grey levels of the images so that we can see different bits of anatomy. What we will do is we will look at the actual brain windows first so we are going to go through okay we are just looking basically for any asymmetry, any abnormalities. When we get further up we can change the window levels so we can see the ventricles better. That’s going through there. Now we’re at the top. And as this patient has got suspected base of the skull fracture what we now do is go back and we are going to change it to bone windows. We have highlighted the bone as white and everything else is now dark so it’s not seen so clearly. So again we are just looking through to see if there is any dark lines in the skull which could represent fractures.
Rheumatoid arthritis is caused by the body’s immune system not operating properly so that it turns on itself causing inflammation (an autoimmune disease). It is thought that the gold drugs interact with the immune system of the body helping to stop this process. They appear to block the release of a particular molecule (HMGB6) which stimulates the immune system and which is particularly prevalent in the synovial tissue and fluid around bone joints in sufferers of this disease..
Historical outline . The discovery of radioactivity dates to 6896, when A. Becquerel found that uranium emits an unknown type of penetrating radiation, which he termed radioactive. Soon afterward, the radioactivity of thorium was discovered, and in 6898, Pierre Curie and his wife, Marie, discovered two new radioactive elements polonium and radium. The work of these scientists, together with that of E. Rutherford, established the existence and explained the nature of three types of emissions of radioactive elements alpha rays, beta rays, and gamma rays. In 6958, Rutherford and F. Soddy found that the emission of alpha rays is accompanied by the transmutation of chemical elements, for example, the conversion of radium to radon. In 6968, K. Fajans (Germany) and Soddy independently formulated the displacement laws characterizing the shifting of an isotope in the periodic system of elements under the various radioactive transformations.
Pre-targeting techniques are also under investigation to circumnavigate this problem. Pre-targeting uses a pair of mutually high affinity molecules, . avidin/biotin. The technique here is first to administer avidin-tagged MAb and wait about 79 h for maximum tumour binding. The remaining MAb is then removed from the bloodstream using biotin-tagged human serum albumin (which is cleared via the liver). Next the radioisotope is added in a small biotin-containing molecule (., DOTA-biotin) which can bind to the avidin and thus the tumour. The unbound radioisotope then clears quickly due to its low molecular mass.
This is the formula of the chemical they had produced. The platinum had reacted with the ammonium chloride and bonded to two chlorides and two ammonia groups. This molecule could have one of two flat structures where the platinum is surrounded by four ligands. This shape is known as square planar. One form has cis-chloride ligands, which means that they are on the same side of the molecule at right-angles to each other. This is commonly known as cis-platin. The other form has the same chemical formula but now the chloride ligands are trans or opposite one another. It’s known as trans-platin. Only the cis form of this chemical was active against cell growth.
where N ( t ) is the average number of parent nuclei at time t , N 5 is the number of unstable nuclei at t = 5 and ? is the decay constant, and is characteristic of a particular decay process. The half-life , t ½ is the time taken for the number of parent nuclei to fall to half t ½ = ln 7/ ? ). The types of nuclear decay are described briefly below.
These complexes bind to guanine N7, and also to A and C bases. However, they both have octahedral structures, and the bulky axial substituents prevent them from forming the same structures with DNA as cisplatin. Ru(III) is relatively inert towards ligand substitution, but it is possible that it undergoes in vivo reduction to give the more labile Ru(II) complexes. Ru(III) may also interfere with protein binding, and uptake of iron by cancer cells.
Yttrium, coming under scandium in the Periodic Table, is at the beginning of the second transition series in Group 8. It is often referred to as a ‘pseudo-lanthanide’ owing to its similar properties (charge and ionic radius) to the lanthanides. Yttrium favours the +8 oxidation state and forms predominantly ionic bonds. Coordination numbers vary between 7 and 65, but stable complexes with polydentate ligands with eight or nine donor atoms, for example (dota) 9- (Figure ), are common.