Contrast agents

Currently, X-rays, magnetic resonance phenomena and ultrasound are used for radiological diagnosis of various diseases of internal organs. The possibilities of any of these types of diagnostics are multiplied by the use of contrast agents, which can be divided into 3 groups:
1) X-ray contrast agents (RKS);
2) magnetic resonance imaging contrast agents (MRKS);
3) ultrasound contrast agents (USS).
While the history of the RCS development began almost immediately after the discovery of V.K. X-ray X-rays in 1895, MRCS and USS have been used in medicine for only a few decades. However, it is precisely among the drugs of these groups of contrast media that the greatest progress has been noticeable in recent years, although new drugs continue to appear in the series of RCCs, which remain the most used means for radiation diagnostics.
According to the classification of P.V. Sergeeva, RCCs are divided into two groups: X-ray negative, transmitting X-rays, and X-ray positive, delaying them. The first group includes carbon dioxide, nitrogen, oxygen, xenon and other gases, the second – iodine-substituted and iodine-free substances.
X-ray positive drugs have a higher density than soft tissue and bone. Density is determined by molecular weight. An increase in the atomic mass of the elements that make up the RCS leads to an increase in the contrasting of the internal organs. The density of soft tissues is approximately equal to the density of water (0.92-1.06 g / cm3), iodine density – 4.94 g / cm3 and barium – 3.51 g / cm3.
Iodine and barium turned out to be the most acceptable elements to be included in the RCC. Barium preparations (sulfate) have been used for contrasting the gastrointestinal tract for half a century, their main advantage is pharmacological inertness, but they are not applicable for contrasting closed cavities or vascular formations.
For the purposes of angiography, urography, cholecystography, myelography and other varieties of these methods, since the 50s, organic iodine-containing RCS are increasingly used.
Among them, ionic and non-ionic monomeric and dimeric iodine-containing PKCs are currently distinguished. According to the results of existing preclinical and clinical studies, non-ionic RCSs, in comparison with ionic ones, have greater safety and better tolerance.
Introduced into medical practice before 1969, iodine-containing organic RCCs are salts that dissociate in aqueous solutions. Their ionic nature and, consequently, hyperosmolarity (5 times higher than blood osmoticity) causes a number of side effects: hypotension, nephropathy, increased capillary permeability, vascular soreness, nausea, vomiting, etc. Therefore, the creation of non-ionic drugs, the osmoticity of which is 2–3 times lower in comparison with ionic RCS. The first such drug was metrizamide (amipak), which was not widely used due to instability. Since the 80s of the last century, stable triiodinated monomeric non-ionic RCCs (iohexol, iopromide, etc.) have been created and introduced, which give the best guarantees to radiologists in terms of diagnostic efficacy and safety. Despite the lower toxicity and better tolerance, non-ionic RCSs, due to their high cost in Russia and a number of other countries, have not yet completely replaced ionic RCSs.
All triiodo-substituted organic RCCs are classified as follows:
I. Ionic.
1. Monomeric
– derivatives of benzoic acid (diatrizoate, ioxitalamate, iothalamate, metrizoate, iodamide),
2. Dimeric
– derivatives of arylaminoacetylaminoiodobenzoic acid (yoxaglate),
– triiodobenzoic acid polymethylene dimers (iodipamide, iodoxamate, iotroxate).
II. Nonionic.
1. Monomeric (iopamidol, iopromide, iohexol).
2. Dimeric (iotrolan, iodixanol).
RCS used for cholegraphy and angiography differ in pharmacokinetics and are administered either orally, intravenously, or intraarterially.
Intravenous cholecystographic substances penetrate cell membranes, are actively secreted by the liver and diffuse into the bile ducts. They are excreted by the liver unchanged.
A certain part of the cholegraphic iodine-containing RCS is excreted from the body in the urine, which must be taken into account when X-ray examination of patients with pathological conditions of the kidneys.
A feature of the pharmacokinetics of angiourographic agents is the circulation in the vascular bed without connection with proteins and the high (partly because of this) rate of their excretion by the kidneys (subject to the normal functioning of the urinary system). They are excreted by the kidneys, usually unchanged.
Based on the study of the mechanisms of transport of PKC, their interaction with plasma proteins, blood corpuscles, membrane structures of the liver and kidneys, the theory of organotropy of PKC was formulated, the essence of which is the existence of transport systems for cholecystographic PKC in cell membranes, functioning according to the principle of molecular “recognition”, and for urographic RCS – special mechanisms of secretion and concentration in the renal tubules.
Adverse reactions to intravascular administration of ionic angiourographic RCS occur in about 12% of cases, and some of them require emergency resuscitation measures. Despite the creation in recent decades of new, less toxic RCS, the problem of the safety of their use remains very urgent.
All side effects caused by PKC are divided into chemotoxic and atopic (anaphylactoid and allergic).
Atopic reactions induced by PKC are due to the release of histamine and other mediators. They are more common in patients prone to allergic diseases and represent the main danger in the clinical use of RCCs. Chemotoxic effects are almost always present and are explained by the osmotic activity of PKC (a decrease in hematocrit due to the release of tissue fluid and water from blood cells into the vascular bed; osmotic diuresis after PKC molecules enter the lumen of the renal tubules), their lipophilicity, electric charge, ability to interact with biomacromolecules, etc. In some parts of the central nervous system there is no BBB, for example, in the postrema area, in which the trigger zones that determine the occurrence of nausea and vomiting are located. The direct effect of contrast agents on these areas (it is the higher, the higher the osmolality of the RCC) and may be the cause of these side effects.
To reduce the risk of developing anaphylactoid reactions, premedication (antihistamines, glucocorticoids, adrenomimetics, etc.) should be used, and chemotoxic reactions (especially important for ionic highly osmotic PKCs) – antiemetics (metoclopramide).
A number of tools are used in magnetic resonance and ultrasound examinations. For example, some gadolinium-containing compounds (Magnevist) increase the contrast of the image of tissues and foci of pathology in the central nervous system and other internal organs during MRI, micronized D-galactose (Levovist) increases (indirectly) the intensity of the reflected echo signal during ultrasound diagnostics.