Radioisotope diagnostics of urological diseases

Modern medical disciplines are impossible without interaction with related specialties, especially diagnostic ones. Successful treatment and its prognosis depend to a large extent on the quality and accuracy of the diagnostic tests. Medical radiology - one of the most important disciplines, occupying from the second half of the twentieth century, a solid place in the diagnosis of a variety of diseases and lesions of internal organs.

Medical radiology is the science of using ionizing radiation for the recognition and treatment of human diseases. It is divided into diagnostic and therapeutic.

High informativeness of the results obtained in combination with ease of implementation and atraumaticity of the study are not the only advantages of diagnostic radiology. Obtaining not only additional information about the functional and structural state of the urogenital system, but also the original diagnostic information, raises the methods of radioisotope indication to one of the main places in the complex of modern urological examination.

The beginning of the use of radioactive indicators in clinical practice falls on the 40s of the XX century, when a strict pattern was established for the distribution of radioactive iodine in various pathological conditions of the thyroid gland. At the same time, diagnostic tests were developed containing radioactive iron for the determination of erythrocytes in various blood diseases, radioactive phosphorus for the purpose of studying malignant growth, and radioactive sodium for the investigation of general and local blood flow in cardiovascular diseases. Since the mid-1950s, when industrial production in a sufficient number of various radioactive nuclides became possible and reliable radiometric devices appeared in circulation, radioisotope methods of research have been introduced into clinical practice in urology. Since then, radioactive methods of research have gained a solid place in the diagnosis of various diseases and lesions of internal organs and have formed into an independent discipline, called nuclear medicine. At the same time, the essence of nuclear medicine was formed, and certain traditions of using specific research methods that formed four main groups were formed.

• Radiography (renography, cardiography, hepatography).
• Scanning organs.
• Clinical radiometry (the study of the volume of various elements by the method of counting the entire body).
• Laboratory radiometry (study of RFP concentrations in the biological environment of the body).

In the 70s of the last century rapid development of new methods of radioisotope research - scintigraphy and radioimmunological methods in vitro - began. They became the main ones and account for about 80% of the total volume of radioisotope diagnostics in modern clinical practice. To carry out a functional radioisotope study, radiopharmaceuticals and radiometric techniques are needed.

Radiopharmaceutical preparations

RFPs are chemical compounds that contain in their molecule a certain radionuclide that is permitted for administration to a person with a diagnostic or therapeutic purpose. The RFP is administered to a patient only in accordance with the "Norms of Radiation Safety".

Biological behavior of radiopharmaceuticals or so-called tropicity - the time of accumulation, passage and excretion from the organ being examined - is determined by their chemical nature. In modern urological practice, several RFPs are used to assess the functional state of the kidney in the studies of cancenae secretion and glomerular filtration. In the first case, the sodium salt of orthoiodohippuronic acid-sodium iodopipurate is used. Despite the relative radio-toxicity of iodine-hippurate sodium, the optimal diagnostic parameters of its transfer in the system of labeled tubules make it possible to use it widely in radioisotope renography and dynamic nephroscintigraphy. Glomerulotropic preparations of pentatech 99mTc are successfully used to determine glomerular filtration. In recent years, thanks to the synthesis of new labeled compounds - tehnemages and sodium iodoppurate, it became possible to reduce the radiation load on the patient, which is especially important in the examination of young children.

Tagged with technetium colloidal solutions are used in the diagnosis of the bone system (osteoscintigraphy), lymphatic system (indirect radioactive lymphography). (indirect radioisotope angio- and venography).

Methods of radioisotope diagnosis

The methods of radioisotope diagnostics used in urology are divided into static and dynamic. To statistical carry:

• static nephroscintigraphy;
• Hepatography: 
• lymphoscintigraphy; 
• osteoscintigraphy. 

The first two methods are currently not used often, since the methods of ultrasound diagnostics are not inferior to the informativeness of radioisotope static methods of studying the kidneys or the liver.

Indirect lymphoscintigraphy is used to detect lymph node involvement by the metastatic process and to assess its prevalence. The low traumaticity for the patient and the simplicity of the method make it possible to perform it on an outpatient basis.

Osteoscintigraphy is used to diagnose metastases of malignant tumors of the genitourinary system. High sensitivity of the method (more than 90%). The probability of false positive results, not exceeding 5-6%, and the ability to detect osteoblastic metastases 6-8 months earlier than radiography, make radioisotope osteoscintigraphy a popular method. The principle of the method is based on the active absorption of a number of RFPs by metastatic foci of the skeleton. RFP is concentrated in structures that are in the process of bone formation (osteoblasts). When carrying out osteoscintigraphy, phosphorus-containing RFPs are used. The level of accumulation of which in different parts of the skeleton is determined by the magnitude of the blood flow, the state of microcirculation. Degree of mineralization and osteoblastic activity. Uneven distribution of RFP. Which goes beyond the usual anatomical and physiological features of its inclusion, is the main sign of pathological changes in the bone system.

A variant of the study is the so-called three-phase osteoscintigraphy, which involves obtaining a series of images and assessing the amount of radioactivity in the lesion in the first 10-30 s (blood flow), 1-2 min (perfusion) and 2-3 h (congestion). However, low specificity leads to false-positive results, especially in elderly patients with osteodystrophic age-related changes.

Dynamic methods mean:

• radioisotope renography;
• dynamic nephroscintigraphy.

To obtain information on the functional anatomical state of the kidneys using special RFPs that actively participate in the physiological processes of the body during the time of redistribution, dynamic methods of radioisotope diagnostics are carried out.

Radioisotope renography since 1956 has been introduced into clinical practice. The study is a method of primary screening for patients with suspected genitourinary system diseases. However, reliably reveals separate violations of the function of each kidney, only if the difference between them exceeds 15% and if the study is conducted in the correct technical conditions. The method is based on the investigation of the process of active canal secretion of the labeled drug by the kidneys and its removal through the bladder into the bladder. The technique consists in the intravenous administration of RFP and continuous recording during 15-20 min of the level of radioactivity above the kidneys with the help of radiocirculation sensors (renograf). The resulting curve is the rhenogram. Consists of three sections:

• vascular, reflecting the distribution of RFP in the vascular bed of the kidney: 
• secretory, process of selective and active accumulation of RFP in renal structures:
• evacuation, representing the process of removing RFP from the kidneys into the bladder.

To determine the true physiological parameters, the patient is in a sitting position during the study.

However, radioisotope renography has certain disadvantages.

• The installation of the detector above the renal area during renography is performed approximately in accordance with known anatomical landmarks, which in some patients (suffering from nephroptosis, having a dystopic kidney, etc.) can lead to incorrect centering and obtaining inaccurate data.
• When registering the dynamics of passing RFP through the kidney, it is not possible to clearly distinguish the contribution to the renogram of the secretory and excretory stages, and therefore the division of the renogram into conventional segments is conditional.
• Registration of radiation over the kidney area includes not only the registration of the drug. Directly passing through the kidney, but also RFP, located in soft tissues, pre-and subject to the body, which also introduces a certain error in the results of the study.
• The clearance curve obtained during registration over the heart area does not provide clear information about the true cleansing of the body from the RFP, since a significant part of the drug is distributed in the intercellular space. Causing the formation of the so-called Hippuran space (especially in patients with chronic renal insufficiency).
• The study of the rate of accumulation of RFP in the bladder, usually performed without an appropriate calibration of the detector in terms of the amount of injected activity on the phantom, gives only an approximate idea of the total renal function.

The principle of the method of dynamic nephroscintigraphy is based on the study of the functional state of the kidneys by recording the active accumulation of the labeled parenchyma of labeled compounds and their removal by VMP. The research is performed on modern single- or multiple-detector gamma cameras with the choice of zones of interest. In the future, a computer visualization of the body is performed to assess the anatomical state and to plot the curves with the calculation of the functional state.

The method consists in the intravenous administration of tubutropic or glomerulotropic RFP and continuous recording of radioactivity for 15-20 min over the renal region. The information is recorded in the memory of a specialized computer and output to the screen, reproducing the phased passage of the RFP through the organ. The dynamics of RFP passing after special computer processing can be reproduced in the form of computer-generated renograms that have segments - vascular, secretory and evacuation, and also in terms of separate regional renal clearance. Only with the help of dynamic nephroscintigraphy is it possible to study the functional activity of various parts of the renal parenchyma.

The method of dynamic nephroscintigraphy in comparison with radioisotope renography has a number of undoubted advantages.

• The performance of dynamic nephroscintigrams is not associated with an error due to improper centering of detectors, since in the field of vision of a gamma camera crystal there is, with rare exception, the entire region of possible location of the kidneys.
• With scintigraphy, it is possible to register the drug in the zone of the perineal tissues, in a form corresponding to each kidney, allowing one to take into account the contribution of hippuran radiation located in the pre- and underlying tissues and to correct the scintigraphic curve.
• With dynamic scintigraphy, it is possible, along with general information on transport of RFP through the kidney, to obtain data on the separate secretory and excretory functions and to differentiate the level of ureteral obstruction.
• Nephroscintigraphy makes it possible to obtain an image of the kidneys sufficient to assess their anatomical-topographical state, in particular for evaluation of the kidneys by segments.
• Renographic curves are free from errors caused by inaccurate calibration of channels, which occurs when using standard renografs, which allows a more accurate quantitative analysis of the status of each kidney function.

The listed advantages of dynamic nephroscintigraphy, in comparison with renography, make it possible to increase the reliability and sensitivity of the study, and a reliable estimate of the function of each kidney is achieved with a difference of 5%.

In specialized urological hospitals equipped with modern equipment, radioisotope renography can be used only in clinical situations not associated with the possibility of severe kidney damage, when an in-depth study of its functional and topographic-anatomical state is required. Urologic diseases, in which it is possible to confine themselves to carrying out isotope renography as an additional method of examination, conditionally include chronic pyelonephritis (without wrinkling of the kidney), ICD (without significant impairment of the excretory function of the kidneys according to excretory urography), hydronephrosis of stage 1, and a number of other diseases, at which anomalies of development or arrangement of kidneys are not revealed.

Absolute indications for dynamic scintigraphy:

• significant violations of the excretory function of the kidney (according to excretory urography)
• all anomalies in the development of the VMP
• changes in the anatomical and topographic location of the kidneys
• hydronephrosis 2 and 3 stages
• hypertonic disease
• large single and multiple cysts of the kidneys, as well as examination of children and patients and after kidney transplantation.

Dynamic nephroscintigraphy helps clinicians in solving a number of questions about the nature of the course of the disease, the prevalence of lesions of the kidney tissue, the specification of the diagnosis, the prognosis, the evaluation of the results of therapy. Features of the pathological process. Even in the absence of other clinical and laboratory manifestations of renal failure, dynamic nephroscintigraphy is able to detect partial impairment of the functional state of secretory and evacuation functions of the kidneys. The greatest value it has for determining the localization of the side of the disease, as well as the level of damage to the kidney tissue - a violation of tubular secretion or glomerular filtration.

In the excretory function of the organism, an important place belongs to the secretion of the near-canalic liquid into the lumen of the tubule of a number of organic compounds. Tuberculosis secretion is an active transport, in which a certain number of carrier proteins takes part that ensure the capture of organic substances and transport them through the proximal tubule to the apical membrane. The appearance in the blood of any inhibitors of the secretory process reduces the number of carrier proteins, and the tubular secretion process slows down. The process of glomerular filtration is passive and occurs under the influence of pressure created by the work of the heart. The glomerular filtration in each nephron is determined by the effective filtration pressure and the glomerular permeability state. And it in turn depends on the total area of the capillary surface through which the filtration takes place, and the hydraulic permeability of each part of the capillary. The glomerular filtration rate (GFR) is not a constant. It is subject to the influence of the daily rhythm and in the daytime it can be 30% higher than at night. On the other hand, the kidney has the ability to regulate the constancy of glomerular filtration, and only with severe glomerular lesions irreversible processes occur. From the point of view of physiology, secretion and filtration are two different processes. That is why conducting dynamic studies with different drugs reflects each of them. In addition, in the initial stages of most urological diseases, the function of the tubular apparatus is affected. Therefore the most informative method of determination will be dynamic nephroscintigraphy with tubulotropic drugs.

The analysis of a large number of results of a combined examination of urological patients allowed the development of a so-called general functional classification of renal and vestibular lesions, based on the main non-specific variants of changes in the system of paired organs.

By type:

• unilateral and bilateral;
• acute and chronic.

According to the form of primary lesion:

• renal circulation
• a tubular apparatus
• glomerular apparatus
• urodynamics of the VMP
• combined disorders of all renal parameters.

By stages:

• initial; 
• intermediate; 
• the final one. 

With unilateral lesion, the contralateral healthy kidney takes on the main functional load. With bilateral damage, other organs are included in the process of cleansing the body, in particular the liver. In patients with chronic organic renal impairment, three forms of pathological changes are identified. The first is characterized by complete intralesional compensation of the cleansing function. The second is characterized by a decrease in the purification capacity of various departments of nephrons. The third is accompanied by a sharp decrease in all renal parameters. It is noteworthy that the second and third forms are equally observed in adults and children. Explanations to this fact are given by morphological studies, which in the first case show significant sclerotic and atrophic processes in the parenchyma of the organ, and in the second - a combination of obstruction of the ureter with congenital disorders of renal tissue differentiation. In the initial stages of development of pathological changes in the kidneys, own mechanisms of compensation are included within the body, the perfusion of the parenchyma increases or the reserve capabilities of the nephrons are mobilized. Decrease in the purifying capacity of the tubular apparatus is compensated by increased glomerular filtration. In the intermediate stage, the compensation of renal function is due to the work of the contralateral kidney. In the final stage of the lesion, the mechanisms of the extrarenal factor of cleansing the organism are connected.

In each specific group of patients, in addition to these nonspecific signs, specific forms of impaired functional renal parameters can be identified. Disorders of urodynamics of VMP are the leading link in the pathogenesis of many urological diseases and the target for diagnostic and therapeutic measures. The problem of the interrelation between the chronic disturbance of the urodynamics of the VMP and the functional state of the kidneys, as well as the prediction of the functional results of surgical treatment is always very urgent. In this regard, the methods of radioisotope diagnostics, which allow non-invasive and relatively simple quantification of the degree of damage of each kidney separately, are widely used in the diagnosis of a functional condition. To determine the degree of functional and organic changes in the renal circulation system, as well as to identify the functional reserves of the affected kidney, radioisotope pharmacological tests with preparations that reduce peripheral vascular resistance and significantly increase renal blood circulation are used. These include preparations of the theophylline group, xanthinal nicotinate (theonikol), pentoxifylline (trental).

Functional parameters of the kidneys are compared before and after the administration of the drug. There are three types of nonspecific reactions to the pharmacological test of pathologically altered kidneys - positive, partially positive and negative.

In obstructive disorders in the urinary system, pharmacological tests are used with diuretics - drugs that block the process of water reabsorption in the distal tubules of the nephron and do not affect the central and peripheral hemodynamics, but only increase the outflow of urine. This group of drugs includes aminophylline (euphyllin). In patients with ICD, three main forms of functional disorders are distinguished.

The first occurs in patients with kidney or ureteral stones, is characterized by a distinct decrease in the intrarenal transit of the labeled drug in combination with a moderate delay in the process of excretion from the kidney. At the second one, a significant decrease in the purifying capacity of the tubular apparatus is observed with a sharp slowing down of the excretion process. The third type is revealed in patients with coral stones, which is manifested by the violation of the drug transit through the vascular bed of the kidney in combination with the predominant disruption of the function of the tubular or glomerular apparatus. When patients are administered radiopharmacological tests with eufillinoy in the presence of reserve capabilities, they establish a positive dynamics of the functional state of the kidney. In the absence of reserve capacities, the deficit of purification, in comparison with the original one, does not change. For this sample two types of nonspecific reaction are characteristic: positive and no reaction.

With lesion of the renal artery and the vasorenal origin of arterial hypertension (AH), a typical functional symptom complex is observed - a distinct decrease in the blood flow and cleansing parameters on the side of the lesion in combination with the lengthening of the time of the intrarenal drug transport. Only the degree of these changes varies. Such functional semiotics is extremely important for the clinical picture of the disease, especially at the stage of screening examination of patients with arterial hypertension. For differential diagnosis in such patients it is necessary to carry out a radiopharmacological test with captopril (kapoten). Comparison of exercise and control studies clearly records the reserve capacity of the vascular bed of the kidneys and renal parenchyma and facilitates the diagnosis of the vasorenal and nephrogenic origin of hypertension.

Modern capabilities of dynamic nephroscintigraphy allow quantitative assessment of the severity of disorders not only secretory. But also the evacuation function of VMP in patients with obstructive uropathies. A close correlation between the severity of urinary passage in the urinary tract and the degree of impaired renal function was confirmed. As in the period of the formation of disturbances in urodynamics, and after the operative restoration of the urine passage through the VMP, the degree of preservation of the evacuation function as a whole determines the severity of renal dysfunction. The most informative indicator is the deficit of blood purification from hippuran. The filtration function of the kidney is not directly related to the state of urodynamics.

The secretory function of the renal tubules is disrupted in proportion to the degree of hemodynamic disorders and is only partially restored depending on the severity of the initial disturbances. When the urodynamics of the VMP disturbed, a reliable correlation was found between the degree of urinary passage disorder and the decrease in the function of the renal tubules. However, the severity of the initial kidney function deficiency does not affect the effectiveness of the reconstructive operation, and the degree of disruption of the evacuation function in the preoperative period is of significant importance for the postoperative operation. If the cause of the pronounced disturbance of urodynamics lies not so much in the mechanical occlusion of the lumen of the VMP, as in the changes that have occurred in the wall of the pelvis and ureter that have led to a significant loss of contractile activity, the elimination of obstruction can not lead to the desired therapeutic effect. On the other hand, with an adequate improvement in urodynamics, the operation gives a positive result, even with an initially significant deficit of purification.

The results of dynamic nephroscintigraphy in patients with vesicoureteral reflux are represented by two forms of functional disorders. In the first case, there is a slight decrease in the purifying function of the tubular kidney apparatus while maintaining the normal values of the remaining functional parameters. The second form differs mainly in violation of the process of excretion from the kidney.

Basically, the problems of physiology and pathophysiology of hormones - the object of research of endocrinologists. Hormones produced by the kidneys, and the kidney effects of other hormones are increasingly interested in urologists and nephrologists. There is an increasing interest in tissue regulators (tissue hormones), such as prostaglandins and histamines produced by the kidneys. Kidneys play a major role in catabolism and excretion of renal and adrenal hormones and thereby participate in the regulation of the hormonal status of the whole organism.

At the end of XX century. A highly effective method for determining the level of hormones in biological fluids was developed and implemented - radioimmunoassay. It consists in the competition between the labeled and unlabeled analogs of the substance under study for a limited number of binding sites in a specific sensing system before the chemical equilibrium of all components of the reaction mixture is reached. Antibodies are used as a specific receptor system, and antigens labeled with a radioactive isotope are used as a labeled analogue. The label does not change the specific immunological specificity and reactivity of the antigen. Depending on the percentage of labeled and unlabeled antigens in the solution, two antigen-antibody complexes are formed. Due to its specificity, high sensitivity, accuracy and simplicity of analysis, the method of radioimmunoassay has replaced many biochemical methods for determining the concentration in biological fluids of hormones, tumor antigens, enzymes, immunoglobulins, tissue and placental polypeptides, etc.

MKB and coral nephrolithiasis is a polyethiologic disease. Violation of calcium-phosphorus metabolism in the body with a certain frequency leads to the formation of kidney stones. The parathyroid hormone produced by parathyroid glands has a huge effect on the maintenance of calcium homeostasis in the body. Parathyroid hormone is metabolized in the liver and kidneys and affects the functional structure of the kidney - it reduces the reabsorption of inorganic phosphates in the proximal tubules. It has an active effect on redox processes in the cells of the renal tubules, stimulates the synthesis of the active metabolite of vitamin D, which is the main regulator of calcium absorption in the intestine. With hyperfunction of para-thyroid gland, the concentration of parathyroid hormone in the blood increases significantly. Nephrolithiasis is the most frequent clinical sign of primary hyperparathyroidism (in 5-10% of ICD patients). The determination of the concentration of parathyroid hormone and calcitonin in the blood is the most accurate method of diagnosing hyperparathyroidism. Since immediately after entering the blood, the parathyroid hormone molecule breaks up into two fragments with different biochemical activity and half-life, in order to reliably determine the level of plasma concentration of its active fragment, it is necessary to take blood for research in the immediate vicinity of its secretion site - from the veins of the thyroid gland. This also allows you to determine the location of the parathyroid gland with increased functional activity. For differential diagnosis of primary and secondary hyperparathyroidism, a gradient of the concentration of parathyroid hormone and calcitonin is determined. The biological effect of the latter is to enhance the excretion of calcium, phosphorus, sodium and potassium by the kidneys and inhibit the resorptive processes in the bone tissue. With primary hyperparathyroidism, the concentration of parathyroid hormone in the blood rises, and calcitonin remains within normal figures or slightly below normal. With secondary hyperparathyroidism, the concentrations of both parathyroid hormone and calcitonin in the blood are increased.

In a complex examination of patients with hypertension, radioimmunoassays in the blood plasma of renin, aldosterone and adrenocorticotropic hormone are mandatory. Renal tissue under conditions of ischemia secretes renin, belonging to the group of proteolytic enzymes, which, when interacting with angiotensinogen, forms a pressor polypeptide-angiotensin. Blood samples for determining renin concentration by radioimmunoassay are taken directly from the renal veins and inferior vena cava before and after the orthostatic load, which makes it possible to reliably detect asymmetry in renin secretion.

No less significant is the role of the adrenal glands producing aldosterone in response to increasing angiotensin stimulation. With prolonged course of vasorenal hypertension (VRG), secondary aldosteronism develops, based on water-electrolyte disturbances, consisting of water retention in the body, increased urinary potassium excretion, arteriolar wall swelling, increased sensitivity to various pressor agents, and an increase in total peripheral resistance . The most potent stimulant of aldosterone secretion is adrenocorticotropin hormone, which also increases the secretion of corticosteroids, in particular cortisol. Increased concentration of cortisol in the blood increases diuresis, has hypokalemic and hypernatremic effects. Consequently, patients with VRH need a thorough radioimmunoassay study of the concentration in the blood of the above substances.

Hypothalamus, pituitary gland and male genital glands form a single structural and functional complex, in the interaction of which there are both direct and inverse connections. The need to determine the concentration of the corresponding hormones in the blood in patients with impaired sexual function and fertility is obvious. Radioimmunological analysis in this area is the most accurate method at present.

The use of radioisotope diagnostic methods in urology is expedient and promising. The possibilities of nuclear medicine for obtaining an objective assessment of anatomical and functional changes occurring in the organs of the genitourinary system are rather multifaceted. However, with the modernization of diagnostic equipment, the release of new RFP preparations, the possibilities of radioisotope methods will be improved, and along with them, diagnostics.

[1], [2], [3], [4], [5], [6], [7], [8]