A Cover Subject On Radioactivity
Radioactive Element
Radioactive elements are in an unstable, high-energy state and emit radiation to return to a stable, low-energy state.
Pollution, Soil
Thomas E. McKone, in Encyclopedia of Toxicology (Second Edition), 2005
Transformation
The transformation of toxic substances in soil can have a profound effect on their potential for human exposure and accumulation by biota. Transformation processes in soil include physical processes such as radioactive decay; chemical processes such as photolysis, hydrolysis, and oxidation/reduction; and biological processes such as microbial transformations. All of these processes can significantly reduce the concentration of a substance or alter its structure in such a way as to enhance or diminish its toxicity.
Radioactive Decay
Radioactive elements are made up of atoms whose nuclei are unstable and give off atomic radiation as part of a process of attaining stability. The emission of radiation transforms radioactive atoms into another chemical element, which may be stable or may be radioactive such that it undergoes further decay.
Photolysis
Most organic contaminants are capable of undergoing photolytic decomposition. Such decompositions can be partial, resulting in the formation of stable by-products, or complete, resulting in the destruction of the compound or organism. Although the atmosphere attenuates solar radiation before it reaches the earth's surface, the solar radiation generally sufficient to break bonds in many compounds at this surface. Phototransformation in soil impacts only those contaminants on the soil surface. However, in agricultural lands that are tilled, contaminants in the tilling horizon (∼15–20 cm) can be brought to the surface where phototransformation occurs. Phototransformations can result in relatively short half-lives (e.g., hours to days) for contaminants such as pesticides that are applied directly to crops or surface soils.
Hydrolysis
Hydrolytic transformation of organic chemicals can be a significant destructive process for toxic compounds that are present in the aqueous phase of soils. Hydrolysis is most important for chemicals that have functional groups (e.g., amides, esters, carbamates, organophosphates), which can be rapidly altered (e.g., minutes to days) in the presence of water. For amides and carbamates, hydrolytic cleavage yields aromatic and aliphatic amines with increased likelihood of toxic activity. Conversely, hydrolytic degradation of compounds that contain stable constituents (e.g., halogenated compounds such as carbon tetrachloride) can have half-lives of several thousand years. Because hydrolytic reactions are driven by the availability of hydrogen and hydroxide ions, the pH of the soil can have a dramatic influence on the rate of hydrolysis for any given compound.
Oxidation and Reduction
Many inorganic and organic chemicals can undergo oxidation or reduction reactions in soil. An indicator of a compound's ability to be oxidized or reduced is provided by its oxidation potential (Eo), which is the voltage at which it is transformed to its reduced state. A similar measure of a soil's ability to reduce a compound is provided by the redox potential (pE), which is a measure of electron activity. Redox potentials are relatively high and positive in oxidized environments (e.g., surface waters), and low and negative in reduced environments (e.g., aquatic sediments and the subsurface soil layers). These environmental conditions are especially important for inorganic chemicals that are rarely present in their elemental form in the environment. Arsenic, for example, exists primarily in its oxidized form (arsenate) in the atmosphere and in surface waters and in its reduced form (arsenite) in sediments.
Microbial Transformation
Due to their broad range of enzymatic capabilities, microorganisms are capable destroying other microorganisms and transforming many inorganic and organic compounds. The chemical transformations can result in the partial degradation of a compound (e.g., conversion of trinitrotoluene to dinitrotoluene), mineralization (i.e., complete transformation to carbon dioxide and water), or synthesis of a stable product (e.g., formation of methyl arsenicals from arsenate). While these processes generally result in the detoxification of the parent compound, toxic products may also be formed. For example, the microbial metabolism of aromatic amines can result in the formation of toxic by-products.
RADIOCHEMICAL METHODS | Natural and Artificial Radioactivity
J. Tölgyessy, M. Harangozó, in Encyclopedia of Analytical Science (Second Edition), 2005
Determination of Natural Radioactive Elements
Naturally occurring radioactive elements can be determined by measuring the activity of the appropriate radioisotopes. These measurements are particularly suitable for radioactive elements with short half-lives. The use of radioisotopes with long half-lives is less suitable, particularly as regards accuracy and sensitivity; even in this case, however, radiometric methods are usually simpler and more rapid than conventional procedures. The basic assumption is that a radioelement has at least one isotope that can be measured; hence the isotopic composition must be known. If an element is known to have a constant isotopic composition, measurements and calculations are relatively straightforward (e.g., potassium, rubidium, samarium, lutetium, rhenium, and francium).
When an element has more than one radioisotope, determinations and data analysis are generally more complex because the isotopes may differ in half-life, especially when a series is involved, e.g., radium, thorium, polonium, radon, actinium, protactinium, and uranium. One possibility is to make measurements after the decay of the short-lived radionuclides, but this may require long waiting times. In favorable cases, it is more convenient to measure the activity of decay products (e.g., radon, thoron (220Rn), actinon (219Rn)), or correct the measurements of the short-lived radioisotopes after determination of the isotopic composition.
Emanometric methods are radioanalytical methods that use measurement of radioactive isotopes of inert gases for the determination of appropriate elements. A good example is the use of the radon isotopes 226Rn, 222Rn, and 219Rn to determine radon, thorium, radium, and actinium. Indirect determinations (e.g., use of radon to determine radium) require both components to be in equilibrium, or present in a known ratio.
In general, these methods require the removal of the inert gas from the sample; the gas is then transferred to a suitable detector. Solid samples must be converted into liquid form such as a solution or a melt (by fusion with sodium carbonate or borax). Once the sample is in liquid form, the gas may be swept out by bubbling air through the solution into an evacuated ionization chamber, by passing a continuous stream of air through the sample and detector, by spraying the liquid using a small air-screw, or by shaking the liquid sample with air. An example of emanation equipment for the determination of thoron is shown in Figure 4. Alternatively, an α-scintillation cell coupled to a photomultiplier can be used.
Radioactive materials
PK Gupta, in Illustrated Toxicology, 2018
Exercise 2
- Q.1
How do radioactive elements produce other radioactive elements?
When atoms undergo radioactive decay, they change into new substances, because they have lost something of themselves. These by-products of radioactive decay are called “decay products” or “progeny.” In many cases, the decay products are also radioactive. If so, they too will disintegrate, producing even more decay products and giving off even more atomic radiation.
- Q.2
What is the difference between ionizing radiation and radioactivity?
A radioactive atom is unstable because its nucleus contains extra energy. When this atom decays to a more stable atom, it releases this extra energy as ionizing radiation.
- Q.3
Is there more than one kind of radiation?
Yes, in addition to x-rays, three are common: the alpha, beta, and gamma radiations. Alpha rays (the nuclei of helium atom) may be stopped by paper, beta rays (high-speed electrons) are stopped less easily, and gamma rays (such as x-rays) may need lead or concrete to stop them.
- Q.4
Will these ionizing radiations make me radioactive?
No, just as light will not make you glow in the dark, a chest x-ray will not make you radioactive.
- Q.5
If ionizing radiation does not make a thing radioactive, how do items become radioactive in a nuclear reactor?
In a nuclear reactor there are billions of free nuclear projectiles called neutrons. When absorbed in a material, they make it radioactive, i.e., it emits its own radiation. This is how radioisotopes are made. There are very few free neutrons in the environment.
- Q.6
Will radiation build up in the body until it gets to a point where it kills you?
No, ionizing radiation does not build up in the body. All radiation will eventually disperse. However, radiation effect may appear, after exposure to a high intensity of radiation, just as you may get sunburn from overexposure to sunlight.
- Q.7
When radiation does not build up in the body, how does it harm a person?
All radiation carries energy that may damage living cells. This damage may cause cells either to die or to change their structure and function.
- Q.8
If anyone gets a dose of radiation, will he die?
Very unlikely, because it would take a very large dose to kill sufficient numbers of your cells to cause death.
- Q.9
Where does natural radiation dose come from?
The major part derives from the decay of natural radioactivity in the earth, most of it from uranium and thorium: they give rise to a radioactive gas called radon in the air we breathe. Radon is present in all buildings. Smaller, and roughly equal, parts of everyday radiation come from cosmic rays and from the natural radioactivity of our food and drink. Some other radiations are man-made.
- Q.10
What are the man-made sources of radiation?
Medical uses of ionizing radiation are the major sources. These include the use of x-rays for radiography and computer tomography, and radiopharmaceuticals in nuclear medicine.
RADIOCHEMICAL METHODS | Uranium
M. Keith-Roach, E.P. Achterberg, in Encyclopedia of Analytical Science (Second Edition), 2005
Introduction
Uranium is a radioactive element that is ubiquitous in the environment, with typical crustal and seawater concentrations of 2.7 mg kg−1 and 3.0 μg l−1, respectively. Uranium-238 and 235U are primordial isotopes and their decay leads to the formation of series of daughter radioisotopes, amongst which is 234U (Figure 1). The natural isotopic ratio of 238U:235U:234U is 99.2745:0.7200:0.0055, and other isotopes (Table 1) are produced by nuclear processes.
| Element | Isotope | t1/2 (years) | Main alpha energies/MeVa |
|---|---|---|---|
| Uranium | 239U | 4.47×10−5 | Beta |
| 238U | 4.47×109 | 4.15 (0.23) | |
| 4.20 (0.77) | |||
| 236U | 2.34×107 | 4.45 (0.22) | |
| 4.50 (0.78) | |||
| 235U | 7.04×108 | 4.37 (0.16) | |
| 4.40 (0.58) | |||
| 234U | 2.46×105 | 4.77 (0.71) | |
| 4.72 (0.28) | |||
| 233U | 1.59×105 | 4.78 (0.15) | |
| 4.82 (0.83) | |||
| 232U | 69.8 | 5.26 (0.31) | |
| 5.32 (0.69) | |||
| Plutonium | 238Pu | 87.7 | 5.46 (0.29) |
| 5.50 (0.71) | |||
| 239Pu | 2.41×104 | 5.14 (0.15) | |
| 5.16 (0.73) | |||
| 240Pu | 6.56×103 | 5.12 (0.27) | |
| 5.17 (0.73) | |||
| Neptunium | 237Np | 2.14×106 | 4.77 (0.25) |
| 4.78 (0.48) | |||
| Thorium | 232Th | 1.41×1010 | 3.95 (0.23) |
| 4.01 (0.77) | |||
| 230Th | 7.54×104 | 4.62 (0.23) | |
| 4.69 (0.76) | |||
| 229Th | 7.34×103 | 4.85 (0.56) | |
| 4.90 (0.10) | |||
| 228Th | 1.9 | 5.34 (0.28) | |
| 5.42 (0.72) | |||
| Radium | 226Ra | 1.6×103 | 4.60 (0.06) |
| 4.78 (0.94) | |||
| Polonium | 210Po | 0.38 | 5.30 (1.0) |
- a
- Values in parentheses correspond to emission probabilities.
Uranium displays multiple oxidation states from +3 to +6, with +4 and +6 being the most common. Uranium(IV) is largely insoluble, as it reacts readily with particle surfaces. Uranium(VI), on the other hand, exists as a di-oxo cation, in solution, which forms stable complexes with oxygen-containing ligands, such as carbonate. This is seen in the high solubility of as anionic carbonate complexes in seawater (e.g., ).
The main use of uranium is as nuclear fuel, with a lesser role in nuclear weapons, and its by-product, depleted uranium, is used in conventional weapon heads. Uranium oxides containing 235U enriched to ∼4% are the most common type of nuclear fuel, although metallic uranium with the natural isotopic ratio of uranium is also used in older technologies (e.g., Magnox). The fuel is bombarded with neutrons to induce fission but, as this process is not 100% efficient and high-energy neutrons result in neutron capture, 236U is also produced. The production and use of nuclear fuel results in significant changes to the natural isotope ratio, and the isotope ratio is therefore an important tool in identifying anthropogenic enhancement of uranium in the environment over variable natural concentrations. Isotope ratio measurements of natural uranium can also be used to examine environmental processes, for example, by using solubility differences between uranium and thorium, which is a precursor of 234U (Figure 1).
The study of uranium covers a wide range of interests, from natural systems with low anthropogenic inputs, to mining spoil heaps and contaminated environments, to quality control of fuel production and waste management. Analytical requirements are therefore highly varied with the need to measure uranium in different phases, from ultra-trace to high concentrations, from total uranium concentrations to high precision isotope ratios. The cost of analysis and availability of instrumentation must also be taken into consideration when selecting the appropriate analytical technique.
A range of sample types require radiochemical separation of uranium from the sample matrix and removal of elements that interfere with accurate measurement. A number of radiochemical separation techniques exist, notably co-precipitation, ion exchange, and solvent extraction. The application of measurement techniques to uranium will be described after a discussion of the sample preparation and radiochemical methods.
Radioembolization for liver tumors
Ahmed Gabr, ... Riad Salem, in Blumgart's Surgery of the Liver, Biliary Tract and Pancreas, 2-Volume Set (Sixth Edition), 2017
Yttrium-90 Microspheres
Overview
90Y is the radioactive element most commonly used for radioembolization. It is a pure β-emitter with a half-life of 64.2 hours, and it decays into the stable element zirconium-90. Tissue penetration of the emissions ranges from 2.5 to 11 mm.
Pretreatment Evaluation
Clinical Evaluation
Clinical evaluation is required to stratify patients according to the Eastern Cooperative Oncology Group (ECOG) performance status, and those with a score greater than two are not considered ideal candidates for this treatment.
Laboratory Workup
The laboratory workup is important to assess the pretreatment functional status of the liver. This should include assessment of liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase), bilirubin, albumin, and tumor markers such as α-fetoprotein (AFP).
Pretreatment Angiography and Coil Embolization
Radioembolization requires pretreatment diagnostic mesenteric angiography (see Chapter 21). The aortogram, superior mesenteric angiogram, and celiac trunk angiogram allow the interventional radiologist an opportunity to study the vascular anatomy of the liver and its surrounding structures in detail. The patency of the portal vein and the presence of arterioportal shunting are assessed. The inadvertent spread of the microspheres is prevented by a meticulous study of the vascular anatomy of the liver and collateral nontarget flow (Covey et al, 2002). Coil embolization of nontarget vessels may be necessary to decrease the unintended deposition of microspheres. Some examples of vessels that may need to be embolized are inferior esophageal, left inferior phrenic, accessory left gastric, supraduodenal, and retroduodenal arteries. The minimal incidence of complications following coil embolization and the grave clinical consequences associated with the inadvertent deposition of microspheres in the stomach, duodenum, or pancreas favor prophylactic coil embolization before radioembolization in select cases.
Technetium-99m Macroaggregated Albumin Scan (See Chapter 17)
The 99mTc-MAA scan is used to assess splanchnic and pulmonary shunting. This pretreatment nuclear scan is important to prevent certain complications associated with the treatment. The proximity of the duodenum and stomach to the liver may make it difficult to assess shunting to these portions of the GI tract by using nuclear medicine scans alone. Thus it is important to correlate the findings of angiography to the findings of the 99mTc-MAA scan. The lung shunt fraction (LSF) is used to calculate the dose delivered to the lungs, and adjustment for this parameter minimizes the risk of radiation pneumonitis that may be seen after radioembolization.
All hepatic vessels are assessed during the angiogram, and the arteries feeding the tumor are studied in detail. As the tumor may parasitize blood flow from surrounding vessels, it is necessary to study its vascular supply in detail. Failure to recognize a vessel supplying the tumor may lead to the incomplete targeting of the lesion and treatment failure. The preprocedure angiogram, 99mTc-MAA scan, and radioembolization can all be performed on the same day in an outpatient setting (Gates et al, 2014).
Available Devices
TheraSphere
TheraSphere (MDS Nordion, Ottawa, ON, Canada) consists of nonbiodegradable glass microspheres with diameters ranging from 20 to 30 µm. It was approved by the Food and Drug Administration (FDA) in 1999 and recently has been approved for use in hepatocellular carcinoma (HCC) patients with portal vein thrombosis (PVT). Vials of six different activities are available; the only difference in the vials is the number of spheres; 1.2 million microspheres are present in a vial with an activity of 3 gigabecquerels (GBq). Each microsphere has an activity of 2500 Bq at the time of calibration. The activity of the vial varies inversely with the time elapsed after calibration.
Dose Calculation for Therasphere.
The calculation of the dose requires the use of three-dimensional reconstruction of the target site to calculate the volume of the liver to be infused. The volume in cubic centimeters is then used to calculate the mass in grams by multiplying it by a factor of 1.03.
The activity (A) in GBq administered to the target area of the liver, assuming uniform distribution of microspheres (Fig. 96B.1A), is calculated using the following formula:
D is the dose administered in Grays, and m is the mass in kilograms. Using this formula, it can be said that a dose of 50 Gy will be administered to 1 kg of tissue if 1 GBq of 90Y is given.
The dose given to the treated mass also depends on the percent residual activity (R) in the vial after treatment and the LSF, which is calculated beforehand. These factors are accounted for in the following formula:
SIR-Spheres
SIR-Spheres (Sirtex Medical, Woburn, MA) consist of biodegradable resin microspheres that have a slightly increased diameter and lower specific gravity per microsphere than TheraSphere. The use of SIR-Spheres was approved by the FDA for metastatic colorectal cancer to the liver in 2002. One vial of 3 GBq is available with 40 to 80 million microspheres, with each microsphere measuring from 20 to 60 µm.
As suggested by the small particle size, the embolic effect of the available microscopic spheres is minimal. They are known to lodge in the precapillary arterioles, but their small size also allows deep penetration into the tumor with minimal changes in the vascular supply to the tumor. It has been suggested that hypoxia of the tumors induced by embolization, instead of anoxia, may lead to the release of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1, which may lead to neovascularization of the tumor and subsequent incomplete necrosis and tumor recurrence.
Dose Calculation for SIR-Spheres.
Three methods for dosimetry of SIR-Spheres are recommended by the manufacturers. The partition method is seldom used, because it is applicable only in special circumstances. The empiric method is outlined in Table 96B.2.
The model of dosimetry for SIR-Spheres is based on whole-liver infusion. The calculated GBq of the whole liver are multiplied by the percentage of the target site as a proportion of the whole liver. The most widely used body surface area (BSA) method is as follows:
A is the activity in GBq, BSA is the body surface area in meters squared, and % tumor burden is the percentage of the liver involved by tumor.
New Concepts
Radiation Segmentectomy
Recently, the concept of radiation segmentectomy has been discussed. This is schematically shown in Figure 96B.1B. The current dosimetry models assume lobar infusion; however, if the tumor is localized to two or fewer liver segments, the interventional radiologist can infuse the dose at the segmental level. This maximizes the dose delivery to the tumor and minimizes delivery of radioactive microspheres to the normal parenchyma (Riaz et al, 2011), an approach that has proven to be a safe and effective method of treatment delivery.
Extended–Shelf-Life Microspheres
Lewandowski and colleagues (2009b) recently published a report on the concept of extended–shelf-life microspheres, which can be used for large or multifocal tumors. As stated above, the difference in vials of different activities is the number of microspheres. If the vials of high activities (more microspheres) are allowed to stay on the shelf longer, the activity per microsphere will decrease. This allows the delivery of a higher number of microspheres to larger volumes of the liver with minimal radiotoxicity to the normal parenchyma (Lewandowski et al, 2009b).
Radiation Lobectomy
An animal study concluded that portal fibrosis was seen after the use of radioactive microspheres (Wollner et al, 1988). Gaba and colleagues (2009) recently published a comprehensive analysis on the concept of radiation lobectomy, whereby infusion at the lobar level was used to treat the tumors. Because of fibrosis of the normal parenchyma, decreases in volumes of the treated lobe were seen. Furthermore, compensatory increases in the volumes of the untreated lobes were also observed. Vouche and colleagues (2013) showed that radiation lobectomy via 90Y is a safe and effective technique to hypertrophy the liver, thus making it more amenable to later resection.
New Concepts
Blood Flow Patterns for Dose Calculation
Kennedy and colleagues (2010) have recently published their analysis on computer modeling of 90Y resin microsphere transport in the hepatic arterial tree. They conclude that computer simulations of both blood flow patterns and microsphere dynamics have the potential to provide insight on methods to optimize microsphere implantation into hepatic tumors while sparing normal tissue.
Transcatheter Yttrium-90 Radioembolization
Radioembolization is a transcatheter therapy performed by interventional radiologists. The tumor is approached by using its arterial supply, and the vial is injected into the vessel feeding the tumor. The distribution of the tumor is the factor that allows the treatment to be selective, allowing delivery to one lobe, or superselective, allowing delivery to one segment. The apparatus for the administration of 90Y is designed to minimize the radiation exposure to those involved in the procedure, but a physicist should be present throughout the case to ensure that proper protocols are followed to minimize accidental radiation exposure. The procedure is performed on an outpatient basis, and the patient is discharged on the same day (Salem et al, 2002).
Americium
I. Malátová, V. Bečková, in Encyclopedia of Toxicology (Third Edition), 2014
Mechanism of Toxicity
The mechanism of action of radioactive elements is usually described by their radiotoxicity rather than their chemical toxicity. Exposure of internal human tissues to americium-241 occurs only after 241Am enters human body, as the range of effects of alpha radiation in tissue is only about a few tens of micrometers. In such cases, cells could be damaged by absorption of energy of alpha particles. When the dose is great enough, cells are damaged to such extent that they cannot repair themselves. When too great a cell population is affected, then adverse effects occur in that tissue. 241Am stays in human and other mammalian organisms for a very long time, so occurrence of stochastic (late) effects is much more probable.
Uranium☆
R.M. Sofield, C. Kantar, in Reference Module in Earth Systems and Environmental Sciences, 2013
Uranium Sources
Uranium is a naturally occurring radioactive element with an atomic number of 92 and is considered a heavy metal. Uranium makes up c. 2–4 mg kg− 1 of the Earth’s crust and can occur as a significant constituent in numerous minerals such as uraninite, pitchblende, carnotite, autunite, torbernite, schoepite, uranophane, and coffinite. Uranium has been mined both for nuclear power and for nuclear weapons and so is present in the ecosphere naturally as a mineral as well as a waste product of the mining and nuclear industries. It can be found at low levels in soils, rocks, and water in nature.
There are 21 different known isotopes of uranium, with half-lives ranging from 1 μs ( 222U) to 4.47 × 10 9years (238U) and atomic masses ranging from 217 to 242 g mol− 1. Table 1 includes the radioactive properties of key U isotopes. Natural uranium has three isotopes: 238U (half-life 4.47 × 109years, energy 4.196 MeV), 235U (half-life 7.038 × 108years, energy 4.598 MeV), and 234U (half-life 2.446 × 105years, energy 4.777 MeV), with abundances of approximately 99.275%, 0.72%, and 0.054%, respectively. The natural uranium isotopes undergo radioactive decay by releasing alpha (α) particles accompanied by weak beta (β) and gamma (γ) radiation. The decay process terminates with the release of stable, nonradioactive isotopes such as 206Pb and 207Pb. The isotopes such as 232, 233, 236 U are the artificial isotopes of uranium that can be produced in reactors by a simple neutron capture by a nucleus of 235U and thorium (e.g., 232Th).
| U isotope | Half-lives (yr) | Natural abundance (%) | Specific activity (Ci/g) | Decay mode | Decay energy (MeV) |
|---|---|---|---|---|---|
| 232 | 68.9 | 0 | 22 | α | 5.3α |
| 233 | 1.59 × 105 | 0 | 9.8 × 10− 3 | α | 4.8α |
| 234 | 2.44 × 105 | 0.054 | 6.2 × 10− 3 | α | 4.777α |
| 235 | 7.08 × 108 | 0.72 | 2.2 × 10− 6 | α | 4.598α 0.21γ |
| 236 | 2.34 × 107 | 0 | 6.5 × 10− 5 | α | 4.572α |
| 238 | 4.47 × 109 | 99.275 | 3.3 × 10− 7 | α | 4.196α |
Uranium in ores can be extracted and chemically converted to uranium dioxide (UO2) or other chemical forms that are usable in the nuclear industry. Enriched uranium (increased 234U and 235U), used as a fuel in nuclear reactors, typically contains 2–4% 235U, and > 90% 235U in nuclear weapons and nuclear submarines. The uranium that remains after the enrichment process is known as depleted uranium (DU), and has less 235U and 234U than the isotopic composition of naturally occurring U. These changes to isotope ratios result in less radioactivity in the DU, but the chemical properties are similar to natural uranium. Depleted uranium is generally used in military armor and armor penetrators due to its high density. It is also used as counterweights on certain wing parts in airplane and helicopter construction, shields for irradiation units in hospitals, and containers for transport of radioactive materials.
Isotopic Labeling Techniques
Greg T. Hermanson, in Bioconjugate Techniques (Third Edition), 2013
1.5 Use of Thiolation Reagents for Direct Labeling to Sulfhydryl Groups
Proteins containing sulfhydryl residues can be labeled with a radioactive element by direct coordination to the SH group through a dative bond (Chapter 3, Section 2.8), avoiding entirely the use of a bifunctional chelating agent. Particularly, reduced sulfhydryls in antibody molecules can be coupled with 99mTc to yield thiol–metal derivatives (Thakur and DeFulvio, 1991; Rhodes, 1991). However, cleavage of disulfide linkages within the antibody can lead to activity losses and fragmentation (Pimm et al., 1991). The required sulfhydryl groups can be introduced into antibodies without disulfide reduction through the use of a thiolation reagent that modifies amine residues within the antibody (Joiris, 1991). Thiolating agents such as 2-iminothiolane or SATA provide efficient ways of introducing multiple sulfhydryl groups for this type of radiopharmaceutical preparation (Chapter 2, Section 4.1).
Site-directed thiolation at carbohydrate residues within the Fc region of antibody molecules may prove to be the best choice for SH group introduction while maintain antigen-binding activity. Ranadive and co-workers (1993) used the heterobifunctional crosslinking agent PDPH (3-(2-pyridyldithio)propionyl hydrazide) (Chapter 6, Section 2.3) to react specifically with oxidized polysaccharide components of monoclonals. The polysaccharide chains are treated first with sodium periodate (Chapter 2, Section 4.4) to generate reactive aldehyde residues. PDPH then is coupled to these aldehydes via its hydrazide end to create stable hydrazone linkages. The other end of the crosslinker, containing a pyridyl disulfide group, is reduced with DTT under mild conditions (25-mM DTT, pH 4.5, 30 min) to produce the free sulfhydryl groups. Since the thiolation occurs only at carbohydrate locations within the antibody, the modification has a better chance of being away from the antigen binding sites, thus preserving immunoglobulin activity. Subsequent treatment with sodium pertechnatate yields the 99mTc derivative on the sulfhydryl groups (Figure 12.3).
Interventional Imaging in the Oncologic Patient
Rony Avritscher M.D., Michael J. Wallace M.D., in Oncologic Imaging: A Multidisciplinary Approach, 2012
Technical Background
Radioembolotherapy consists in the TACE delivery of microspheres loaded with radioactive elements, most commonly yttrium-90 (90Y). Using the same principle as other locoregional liver therapies, radioembolization relies on the preferential arterial supply to liver tumors.26,27 Conventional radiation therapy does not have a central role in the management of patients with liver tumors, primarily because of the low tolerance of the whole liver to external beam radiation.45 The risk of radiation-induced liver disease (RILD) after whole liver radiation therapy delivering between 28 gray (Gy) and 35 Gy over 3 weeks is approximately 5%,46,47 and these doses are far less than those needed to adequately treat these lesions. Hence, delivery of the microspheres into the hepatic artery allows deposition of the particles predominantly within the tumor vascularity leading to tissue damage, while preserving the surrounding liver parenchyma. Hence, this critical feature allows delivery of substantially higher radiation doses than what can be safely accomplished by external beam radiotherapy. 90Y is a beta emitter with a 64.1-hr half-life. The beta radiation travels an average of 2.5 mm (maximum 11 mm), a desirable feature because it helps minimize untoward damage.
Currently, two radioembolotherapy devices are approved for use in the United States. TheraSpheres (glass microspheres) are U.S. Food and Drug Administration (FDA) approved for neoadjuvant treatment of unresectable HCC in patients with portal vein thrombosis or as a bridge to transplantation. SIR-Spheres (resin microspheres) are approved for the treatment of metastatic colorectal cancer to the liver with concomitant use of floxuridine. Individual resin microspheres measure approximately 30 µm in diameter with 50 Bq of activity. A whole liver resin microsphere treatment averages an activity of 2 GBq. Glass microspheres have a diameter of 25 µm with an activity of 2500 Bq per sphere. Single-dose whole liver treatment using TheraSpheres have an activity of 5 GBq. Therefore, a treatment using resin microspheres requires a much greater number of particles, which leads to vessel embolization.
Terrorism: Nuclear and Biological Terrorism
Anil Aggrawal, in Encyclopedia of Forensic and Legal Medicine (Second Edition), 2016
Radioactive Contamination
This is another simple terrorist scenario involving nuclear terrorism. Today radioactive elements are used for a number of legitimate purposes. These include nuclear power and engineering, metallurgy, geology, mining, meteorology, chemical and petroleum industries, medicine, and agriculture. Among others, 60Co is used to irradiate food to kill pathogens and in cancer treatment, 137Ce in medical and scientific equipment, 241Am in smoke detectors and engineering gauges that measure moisture content in asphalt, tritium for emergency-exit signs that glow in the dark, 192Ir in cameras that detect flaws in concrete and welding, and 63Ni for chemical analysis. Almost all countries have these radioactive elements and these can potentially be acquired very easily. Once radioactive material is acquired, it could be used to contaminate a number of commodities, such as public drinking water and foodstuffs. It could also be placed at public places, agricultural land, apartment houses, production facilities, storehouses, and transport communications. Such a device is called a ‘simple radiologic device’ (SRD).
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