Accumulation Of Radiopharmaceutical Research Articles

Responsive and traceless assembly of iron nanoparticles and 131I labeled radiopharmaceuticals for ferroptosis enhanced radio-immunotherapy

Ferroptosis is an iron-dependent form of programmed cell death with the potential to reverse traditional cancer therapy resistance. The combination of ferroptosis with chemotherapy, photodynamic therapy and X-ray therapy has demonstrated remarkably improved therapeutic efficiency. Radiopharmaceutical therapy (RPT) is an emerging approach that achieves precise radiation to diseased tissues via radionuclide delivery. However, insufficient accumulation and retention of therapeutic radiopharmaceuticals in tumor region as well as cancer radioresistance impact treatment efficacy. Here, a nanoassembly of renal clearable ultrasmall iron nanoparticles (USINPs) and 131I-aPD-L1 is prepared via the affinity of fluorophenylboronic acid modified on the USINPs with 131I-aPD-L1. The 150 nm USINAs(131I-aPD-L1) nanoassembly is stable in blood circulation, effectively targets to the tumor and disassembles in the presence of ATP in the tumor microenvironment. Both in vitro and in vivo experiments prove that USINPs-induced ferroptosis boosted the tumor radiosensitization to 131I while 131I-mediated RPT further enhanced ferroptosis. Meanwhile, the immunogenic cell death caused by RPT and ferroptosis combined with PD-L1 immune checkpoint blockade therapy exhibits a strong antitumor immunity. This study provides a novel way to improve the tumor accumulation of ferroptosis inducer and radiopharmaceuticals, insights into the interaction between RPT and ferroptosis and an effective SPECT-guided ferroptosis-enhanced radio-immunotherapy.

Pathologic outcome of incidentally detected tracer-avid lesions in 68Ga-PSMA-11 PET/CT for prostate cancer

Abstract Background Prostate-specific membrane antigen (PSMA) PET is effective in identifying prostate cancer metastases. However, PSMA PET uptake has also been described in other lesions, including nonprostate malignancies and benign processes. Purpose To identify causes of unexpected radiopharmaceutical accumulation on PSMA PET. Materials and Methods A total of 2,054 study reports representing 1,873 unique patients who had undergone 68Ga-PSMA-11 PET/CT scans at a single large academic center from December 2015 to April 2022 were retrospectively reviewed for the mention of unexpected PSMA uptake not initially thought to represent metastatic prostate cancer. Scans with pathologic outcome were reviewed by 2 blinded readers for scan indication and lesion location and quantitative parameters. Results In 48 patients, the PSMA ligand–avid incidental lesions revealed 19 cases of second malignancies, 17 cases of prostate cancer, and 13 cases of benign lesions. The most common lesion locations were lung (14), thyroid (14), lymph nodes (8), and bowel (4). Benign lesions exhibited lower molecular imaging PSMA scores (median: 1; interquartile range [IQR]: 1.00-1.25; P = .017) than metastatic prostate lesions (median: 2; IQR: 1-3). Second malignancies were larger (median: 34 mm; IQR: 27-39 mm) than metastatic prostate cancer (median: 14 mm; IQR: 12-19 mm; P = .001) and benign lesions (median: 19 mm; IQR: 13.00-31.00 mm; P = .03). PSMA ligand–avid lesions in scans performed in the initial staging for prostate cancer were more commonly associated with a diagnosis of a secondary malignancy than with metastatic prostate cancer (0 vs 8 lesions, P = .008). Higher standardized uptake value maximum was observed for metastatic prostate cancer and second malignancy when compared with benign outcome. Conclusion Features that influence the probability of an incidental lesion representing a malignancy include lesion location, reason for the PSMA PET/CT study, and associated imaging features (size, standardized uptake value maximum, and molecular imaging PSMA score).

Diagnostic capabilities of PET/CT with <sup>18</sup>F-DOPA in biochemical recurrence of medullary thyroid carcinoma: a retrospective study

INTRODUCTION: Medullary thyroid carcinoma (MTС) is a rare neuroendocrine malignant neoplasm of the thyroid gland. In most cases, sporadic MTС is diagnosed at late stages due to the absence of specific symptoms. The main method of treatment of MTС is surgical — thyroidectomy and in most cases cervical lymphodissection. Current international guidelines suggest the use of basal calcitonin levels and cancer embryonic antigen (CEA) as markers of biochemical recurrence. In biochemical recurrence of the disease, it is advisable to search for tumor foci regardless of the level of cancer markers. Positron emission tomography combined with computed tomography (PET/CT) has the highest sensitivity and specificity for searching for local recurrence and distant metastases. Anatomical imaging methods (computed tomography (CT), magnetic resonance imaging (MRI)) have suboptimal sensitivity and specificity in detection of a recurrent tumor.OBJECTIVE: To explore the diagnostic capabilities of PET/CT with 18F-DOPA in patients with biochemical recurrence of medullary thyroid carcinoma, depending on the concentration of calcitonin in blood plasma.MATERIALS AND METHODS: To evaluate the diagnostic capabilities of PET/CT with 18F-DOPA in patients with biochemical recurrence of medullary thyroid carcinoma, 81 PET/CT studies were analyzed in patients after thyroidectomy. In most cases (76/81), at the time of the study, patients had elevated basal calcitonin levels (>10 pg/ml, including in 52/81 cases >150 pg/ml), which corresponded to a biochemical recurrence of the disease. In 6 cases, the calcitonin level was <10 pg/ml. PET/CT results were processed by visual image analysis, measurement of a semi-quantitative indicator of the maximal standardized level of radiopharmaceutical accumulation normalized to lean body mass (SUVlbm max) and the total volume of PET-positive tumor tissue (metabolic tumor volume).RESULTS: In 41 studies, foci of pathological accumulation of 18F-DOPA were identified, corresponding to recurrent tumor foci. DOPA-negative results in patients with elevated calcitonin levels were regarded as false negative. The highest sensitivity of the method was achieved at calcitonin levels >150 pg/ml. A noticeable positive correlation was found between the concentration of basal serum calcitonin, the number of pathological foci of 18F-DOPA hyperaccumulation and the total metabolic volume of tumor tissue. In most cases of biochemical recurrence, the PET method was superior to the CT method in detecting recurrent tumor foci.CONCLUSION: PET/CT with 18F-DOPA is the most informative method for molecular and structural imaging in patients with biochemical recurrence of medullary thyroid carcinoma. The results of the study directly correlate with the level of basal calcitonin in the blood.

Assessment of arterial blood flow in the microvasculature of the lower extremities in patients with chronic ischemia using a single-photon emission computed tomography (SPECT)

Introduction. Obliterating atherosclerosis of the lower extremity vessels is a chronic, steadily progressive disease of the leg arteries, with a high risk of limb amputation and death. Timely diagnosis and adequate treatment will help slow the disease progression, maintain the patient’s good health for a long time and avoid complications. Purpose. To study arterial blood flow in the microvasculature of the lower extremities, to qualitatively and quantitatively assess perfusion disturbances in functionally significant muscles of the lower extremities. Material and methods. Radionuclide examination of the main vessels and microvasculature of the lower extremities was performed in 36 patients, five of them with a diagnosis of lower extremity obliterating atherosclerosis in dynamics. Radiopharmaceuticals was administered through a catheter installed endovascularly above the aortic bifurcation when patients underwent arteriography of the lower extremity vessels, which also involves intra-arterial administration of a radiopaque contrast agent. Results. When processing the radiological study results, we visually assessed the distribution of radiopharmaceuticals in the vascular bed of the lower extremities, identified the asymmetry in the accumulation of radiopharmaceuticals as a percentage, quantified the accumulation of radiopharmaceutical pulses in the projection of the pelvic, thigh, leg and foot muscles, determining the level of accumulation in each of the areas of interest as a percentage. The radiological study results and direct aortic arteriography of the lower extremities with determination of the level of arterial stenosis confirmed the ischemic nature of the pain syndrome; and in the control study, the effectiveness of treatment with an improvement in perfusion parameters. Conclusions. Intra-arterial administration of radiopharmaceuticals makes it possible to assess the condition of the peripheral arterial bed, which has a significant role in the prognosis of lower extremity atherosclerosis and the results of reconstructive interventions. The method makes possible a hybrid topometric comparison of arterio-perfusion maps for diagnosis, planned treatment and monitoring of its results in dynamics.

Quantitative analysis of standardized uptake values (SUV) of metastatic bone lesions in scintigraphy with [99mTc]Tc-EDDA/HYNIC-Tyr3-octreotide in patients with neuroendocrine tumours.

Neuroendocrine tumours (NETs) are a group of cancers that can produce hormones and other metabolically active compounds. The majority of NETs have specific tissue characteristics, such as the expression of somatostatin receptors (SSTR). Metabolic testing with [99mTc]Tc-EDDA/HYNIC-Tyr3-octreotide ([99mTc]Tc-EDDA/HYNIC-TOC) can be used in patients with NETs to visualize the presence of receptors in different locations of pathological lesions, including the skeletal system. The study aimed to calculate the body weight maximum standardized uptake value (SUVbwmax) of pathological bone lesions and healthy bone tissues, estimate the size of lesions, and identify a relationship between the SUVbwmax of the bone tissues, age and body mass of the study participants. The somatostatin receptor scintigraphies (SRS) with [99mTc]Tc-EDDA/HYNIC-TOC were carried out at the Department of Nuclear Medicine, University Clinical Hospital No. 1, Pomeranian Medical University (PMU) in Szczecin from 2019 to 2022. Whole body and single photon emission computed tomography/computed tomography (SPECT/CT) scans were performed four hours after the injection of 700-800 MBq of [99mTc]Tc-EDDA/HYNIC-TOC in 344 patients with neuroendocrine tumours of various primary lesion locations. In 19 patients, who showed foci of increased radiopharmaceutical accumulation in bone location, the SUVbwmax was measured. The SUVbwmax of pathological bone lesions and healthy tissues were determined on SPECT/CT cross-sectional images using Xeleris 4 software. The total number of foci with increased SSTR expression in bone regions seen on scintigraphic images was 89. Among them, 32 bone lesions were visible on the corresponding CT scans. The mean SUVbwmax of these lesions was 31.39 [standard deviation (SD) 34.31]. For the other 57 lesions that were not visible on corresponding CT scans, the mean SUVbwmax was 19.12 (SD 24.24). The smallest bone lesion detected on the scintigram and visible on the corresponding CT location was 5 mm × 5 mm, measured in cross-section, and was located in the Th8 vertebral body; the largest, measuring 20 mm × 22 mm, was detected in the L3 vertebral body. The SUVbwmax of these lesions was 24.70 and 142.40, respectively. Bone lesions seen on SPECT/CT in [99mTc]Tc-EDDA/HYNIC-TOC scintigraphy can be quantitatively analysed using the SUV index. Even a very small pathological bone lesion can be detected on [99mTc]Tc-EDDA/HYNIC-TOC scintigraphy. It was shown that in cases where bone lesions were visible on CT scans, the SUVbwmax of bone tumour lesions was higher than when lesions were not visible on CT. Body mass does not affect the SUVbwmax of bone lesions. SUVbwmax of healthy bone tissue decreased with age.

Clinical observation of Erdheim–Chester disease: diagnostic difficulties, treatment options

As is known, orphan diseases, which include histiocytosis, including Erdheim-Chester disease (ECD), occur under the guise of other diseases, which complicates timely diagnosis and treatment. The presence of various symptoms in patients with an unspecified diagnosis (weight loss, fever, chills, night sweats, malaise, shortness of breath, thirst, polyuria; pain in the muscles and joints, in the long tubular bones of the upper and lower extremities, in the lower back or abdomen due to kidney damage and/or retroperitoneal fibrosis; exophthalmos; rash, xanthomas; frequent infectious diseases; nystagmus, ataxia, dysarthria) requires doctors to be wary of BEC.The variety of symptoms is due to the involvement of many organs and systems (orbits, kidneys, skin, brain, including the pituitary gland; lungs; heart; blood vessels; tubular bones), which requires a thorough examination, including morphological verification of the pathological process. Histological examination of biopsy specimens for BEC is characterized by histiocytic infiltrates (so-called “foamy histiocytosis”) with signs of inflammation and the presence of Touton giant cells; Immunohistochemistry reveals positive staining of these giant cells for CD68 antigen and factor XIIIa. Bone scintigraphy reveals a pronounced symmetrical accumulation of radiopharmaceuticals in the affected bones; with radiography in places of ossalgia — significant symmetrical bilateral osteosclerosis of the periosteum; according to CT data - “hairy” kidneys, “lined” aorta as a result of infiltration with histiocytes. The BRAF V-600E gene mutation, detected in half of the cases, in combination with one or more clinical and morphological signs allows a correct diagnosis to be made. The treatment of this disease is quite complex due to the lack of multicenter international clinical studies due to the rare occurrence of this pathology. However, clinical studies are currently being conducted on the use of drugs of various groups in the treatment of BEC. There is no doubt that due to the rarity of the disease and the low awareness of doctors, our own clinical experience in managing such patients is of great interest.

A pictorial view on false positive findings of 68Ga-PSMA-11 PET/CT and their prognostic value in patients with prostate carcinoma after radical prostatectomy and undetectable PSA values.

Recently, gallium-68-prostate-specific membrane antigen-11 (68Ga-PSMA-11) positron emission tomography/computed tomography (PET/CT) has become a key imaging method in prostate carcinoma staging and biochemical progression, with varying sensitivities in different studies (from 40% to 80%). After four years of experience with 68Ga-PSMA-11 PET/CT, we found that it is possible to detect lesions with increased PSMA expression in patients with undetectable prostate specific antigen (PSA) levels after radical prostatectomy. The key questions we wanted to answer were as follows: if those lesions were malignant and could the early detection of those malignant lesions have a role in patient management? We aimed to identify and follow up PSMA-positive findings for a period of 4 years in patients with prostate cancer after radical prostatectomy and undetectable PSA values at the time of the examination. We also explored false-positive lesions in detail. The study included all patients who underwent radical prostatectomy and had undetectable PSA values <0.05ng/mL and who underwent 68Ga-PSMA-11 PET/CT between July 2019 and December 2019. We performed 220 studies and found 40 patients with these characteristics; these patients were included in this study. All of them were followed up until July 2023. Any finding with increased radiopharmaceutical accumulation above the background activity in the respective area was considered a false positive. Prostate-specific membrane antigen accumulation in established lesions was assessed semi-quantitatively by the maximum standardized uptake value (SUVmax) and qualitatively by the four-point visual scale proposed in the E-PSMA recommendations. We found 15/40 (37.5%) patients with PSMA-positive findings. These were predominantly bone changes without a corresponding CT abnormality or discrete cystic or osteoblastic lesions with above-background increased PSMA expression. The mean SUVmax of these non-specific lesions was 3.02 (SD 2.86). After 3.5-4 years of follow-up, biochemical progression was found in only two of the patients.The great sensitivity of the method nowadays is a powerful engine for the development of new therapeutic options. On the other side, the lower specificity due to false positive findings, if misinterpreted, might lead to switching to a higher stage, with the planned radical treatment replaced by palliative treatment. The presence of 68Ga-PSMA-11 PET/CT-positive findings in patients after radical prostatectomy and an undetectable PSA had a low predictive value for future progression. The interpretation of 68Ga-PSMA-11 PET/CT should always include a complex assessment of the clinical setting-the risk group, PSA value and degree of PSMA accumulation in the lesions. In these situations, further clarification of PSMA-positive findings is appropriate before deciding to change treatment.

Доклиническое изучение терапевтической эффективности радиофармацевтического препарата [Lu-177]Lu-PSMA I&amp;T

The appearance of radiopharmaceuticals based on prostate-specific membrane antigen (PSMA) ligands labeled with beta- or alpha-emitting radionuclides led to a breakthrough on the development of targeted therapy for metastatic castration-resistant prostate cancer. For the completeness of the preclinical evaluation of therapeutic radiopharmaceuticals based on PSMA, the study of their effectiveness should be supplemented by an assessment of absorbed doses of internal radiation in experimental tumor foci. The objectives of this study were: 1) Examine the dose-effect relationship to assess the therapeutic efficacy of [Lu-177]Lu-PSMA I&amp;T with activities comparable to those of humans; 2) Assessing the expected absorbed dose levels created in 22RV1 xenografts after the therapeutic effects have been introduced, with the potential for both minimal and maximum radiopharmaceutical accumulation. The studies were conducted on male nu/nu mice with subcutaneous 22RV1 xenografts. The dynamic of accumulation was examined after 2.2 MBq of a radiopharmaceutical was introduced. The main findings were obtained when [Lu-177]Lu-PSMA was introduced at 9.2 MBq (EDmin) and 36.6 MBq (EDmax). A statistically significant dose-dependent inhibition of xenograft growth was found compared with the control. The expected absorbed doses for EDmin in xenografts were between 2.7 Gy for minimal accumulation and 3.9 Gy for maximum accumulation. For EDmax in a similar scenario, this range was 10.7 to 15.5 Gy. The results support the preclinical assessment's informationality in determining the range of doses absorbed in tumor foci that cause the observed therapeutic effects.

Experience in Using Breast Single-Photon Emission Computed Tomography with &lt;sup&gt;99m&lt;/sup&gt;Tc-MIBI

Objective: evaluation of the results of single-photon emission computed tomography (SPECT) with technetium-99m-methoxyisobutylisonitrile (99mTc-MIBI) in women with breast masses according to mammography (MMG) and ultrasound (US) examination in comparison with the results of morphology analysis.Material and methods. SPECT with 99mTc-MIBI was performed in 11 women aged from 30 to 63 years (median age 40 [33.5; 46.5]) with BI-RADS (Breast Imaging Reporting and Data System) categories 4 or 5 mammary masses according to bilateral MMG and US diagnostics. Two patients underwent repeated SPECT and US to analyze the primary tumor response to neoadjuvant chemotherapy.Results. With a multimodal approach to the diagnosis of breast tumors, including MMG and US, 11 pathological masses were identified. SPECT made it possible to find an additional mass that had not been previously visualized. All 12 masses were subsequently verified morphologically. With benign changes, hyperfixation of 99mTc-MIBI was not observed. SPECT allowed to assess the accumulation of the radiopharmaceutical in metastatically affected lymph nodes. However, the most sensitive method for detecting the axillary lymph node lesions is US. According to the results of repeated SPECT in 2 patients, no radiopharmaceutical accumulation was noted in mammary gland masses after two courses of neoadjuvant chemotherapy, but according to the histological examination, the tumor response was different: I and IV degrees of pathomorphosis according to G.A. LavnikovaConclusion. The experience of using mammary SPECT with 99mTc-MIBI confirms an increase in the accuracy of radiologic diagnosis of newly identified breast cancer, expands the possibilities of examination in cases of ambiguous MMG and US data, as well as the contraindications or patient’s refusal from magnetic resonance imaging.

Scintigraphic signs of kidney injuries of I–IV degrees of severity and their compliance with the OIS/OI AAST classification: observational study

INTRODUCTION: Mechanical effects on the kidney result in parenchymal disruption, haemorrhage formation, classified by OIS/OI AAST. Scintigraphy with 99Tc-DMSA can determine the presence, prevalence of areas of ischaemia and implications for renal function.OBJECTIVE: By radiopharmaceutical accumulation, to assess the function of the injured kidney and to establish the consistency of the scintigraphic images with the radiological findings of the OIS/OI AAST classification.MATERIAL AND METHODS: Scintigraphy with 99Tc-DMSA was performed in the immediate posttraumatic period in 196 patients who had Grade I–IV organ damage according to the OIS/OI AAST classification. The shape, size, and contours of the kidneys were visually evaluated. Based on the calculation of the uniformity and intensity of the indicator inclusion in the parenchyma the relative (total) kidney function was established. The degree and localisation of kidney damage were revealed on the basis of primary ultrasound and MSCT results.RESULTS: In the acute period of injury, Grade I–II were characterised by diffuse irregular distribution of 99Tc-DMSA (from 75.0 to 100% of cases), but with increasing area and volume of injury, focal scintigraphic symptoms appeared (up to 25.0% of cases).In Grade III–IV, localised or extended focal deformation of the image contour and reduction of the overall kidney function prevailed. Comparative evaluation of CT findings with visual scintigraphy data demonstrated symmetry of visual information with sufficient accessibility, perceptibility, accuracy and correlated with OIS/OI AAST classification.DISCUSSION: Scintigram interpretation involves the interaction of two components: visual perception and subject-specific knowledge of human anatomical structures. This significantly differentiates it from clinicians’ conventional conception of the diagnostic process. Semiotics in the images included diffuse and focal changes, the basis of which is a disorder of haemocirculation with impaired uptake of radiopharmaceutical in the kidney parenchyma. For Grade I–II, hypoactive areas indicating the absence of significant damage are typical. Grade III–IV are characterised by localised areas due to reduced volume of functioning parenchyma.CONCLUSION: Scintigraphy in blunt kidney trauma demonstrates haemocirculatory abnormalities in the organ and a decrease in the amount of functioning parenchyma. Comparison of radionuclide images with computer imaging has a high degree of identity. The type of scintigrams allows grading them according to the OIS/OI AAST degree systematisation, which standardises the interpretation of radiological findings to improve the objectivity and quality of the study reports. Assessment of overall renal function makes it possible to predict the rehabilitative outlook of the injured kidney and the need for correction.

Navigating radiopharmaceutical dynamics in Ra-223 alpha emitter radiotherapy: Implications for treatment optimization and personalization

It has recently come to light that radiotherapy with Ra-223 (alpha emitter) radionuclides can be an effective therapeutic option for a variety of different cancers. A comprehensive knowledge of biodistribution, accumulation, and clearance pathways, as well as radiopharmaceutical kinetics, is required for an accurate assessment of therapy efficacy and a reduction in the severity of any adverse effects that the treatment may cause. Using the absorbed dose, measured in mGy/MBq, researchers can explore each organ in adult male and female animals and the differential accumulation, removal rates, and clearance pathways of radiopharmaceuticals. Because of their high linear energy transfer (LET) and limited range in tissue, the use of alpha emitter radionuclides in radiotherapy has attracted substantial interest recently. These properties allow for targeted therapy with minimum damage to the healthy cells in the surrounding area. This article provides a complete literature analysis on applying alpha emitter radionuclides in radiotherapy. The review focuses on zutilizing two well-known software tools, WinAct 1.0 and IDAC-Dose 2.1, for dosimetry calculations and treatment planning. The findings highlight the significance of tailored dose planning, organ-specific adverse effects, optimum treatment regimens, the potential for combination therapies, and the advancement of radiopharmaceutical development.

Right ventricular visualization at SPECT perfusion imaging before and after revascularization in patients with postinfarction cardiosclerosis

Aim. To evaluate the intersystemic (between the myocardium of the left coronary artery system and the right coronary artery system redistribution mechanisms of perfusion in the myocardium after revascularization in patients with coronary artery disease with focal cardiosclerosis using gated single photon emission computed tomography. Сardiosclerosis foci were initially identified by magnetic resonance imaging. Material and Methods. The study included 17 patients with coronary artery disease with multivessel coronary disease and large-focal cardiosclerosis according to the results of magnetic resonance imaging with contrast; the diagnosis of left ventricular aneurysm was established in 14 patients, the focal subendocardial cardiosclerosis was diagnosed in 3 patients. For various reasons, all patients underwent myocardial revascularization without the left ventricle reconstruction (coronary artery bypass grafting in 10 patients, percutaneous coronary intervention in 7 patients). Magnetic resonance imaging was used as the gold standard for focal cardiosclerosis before revascularization. All patients before and after revascularization underwent gated single photon emission computed tomography with MIBI scan. During the initial analysis of peaks on the profile slices of coronal and transversal midsections passing along the lateral walls of the left and right ventricles, we did not notice a clear visualization of in 8 patients (group 1), while an increased MIBI scan accumulation in the right ventricle myocardium was clearly visualized in 9 patients (group 2). Based on the peaks height of profile curves, we compared changes in the maxima of radiopharmaceutical accumulation before and after revascularization in the lateral walls of the left ventricle and right ventricle. All studies were performed using the original Cardiac Functional Imaging medical program in order to obtain quantitative information about the myocardial function of both the left ventricle, and also the right ventricle. This program made it possible to highlight the right ventricle area even in the case of its weak visualization through the initial formation of parametric images, where the right ventricle area was visualized. Results. When comparing the revascularization results of the two groups, we noted that the left ventricle ejection fraction increased significantly only in patients without initial visualization of the right ventricular myocardium. Left ventricle ejection fraction did not change after revascularization in patients with initially increased accumulation of the radiopharmaceutical in the right ventricle. Globally, only an improvement in the diastolic function of the left and right ventricles was noted in the latter group of patients. In addition, an increase in the right ventricular uptake level was noted for patients with focal cardiosclerosis and the initially increased uptake in the right ventricle after the maximum possible complete myocardial revascularization, which may indicate a redistribution of perfusion in favor of a more intact right ventricular myocardium. Conclusions. 1. In patients without signs of increased visualization of the right ventricle (group 1) after revascularization, we revealed a statistically significant increase in the left ventricle ejection fraction (p-value=0.024), a decrease in the end-systolic volume (p-value=0.024), an increase in the motion in segments corresponding to the peri-infarct scar zone (p-value=0.016), and a change in systolic thickening in the segment of the basal parts of the anterolateral wall (p-value=0.046). 2. Initially increased visualization of the right ventricle in patients with extensive focal cardiosclerosis in the myocardium of the left ventricle suggests the absence of the left ventricle ejection fraction increase after myocardial revascularization. 3. An increase in the visualization of the right ventricle after complete myocardial revascularization indicates an intersystemic redistribution of perfusion in favor of the preserved myocardium of this part of the heart.

KIKUCHI-FUJIMOTO DISEASE: THE FIRST CLINICAL OBSERVATION OF A RARE CASE IN KAZAKHSTAN

Relevance: Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare underlying cause of benign lymphadenopathy, typically accompanied by fever and fatigue. Diagnosing this rare condition causes difficulties. Even though more than half a century has passed since the first described case, KFD is still hard to diagnose. Therefore it is of utmost importance to perform all the necessary diagnostic tests to avoid misdiagnosing and prescribing the wrong and often too-aggressive treatment. This article describes the first clinical case of KFD in the Republic of Kazakhstan.&#x0D; The study aimed to share the clinical course and the specifics of a diagnostic search involving histological and immunohistochemical tests in KFD.&#x0D; Methods: The paper describes a clinical case of KFD.&#x0D; Results: We reported a case of KFD in a 35-year-old man who applied for cervical lymphadenopathy and fever. The diagnosis was made on histological and immunohistochemical analysis of a lymph node. Rapid regression of lymphadenopathy marked the evolution of the disease.&#x0D; Conclusion: This clinical observation describes a rare case of KFD; its cases have not been previously described in Kazakhstan. KFD is prone to the benign course and spontaneous regression. However, difficulties remain in KFD diagnosis since symptoms such as lymphadenopathy and fever more often resemble lymphoma or tuberculosis. Non-tumor lymphadenopathy can also produce high metabolic activity manifested by an intensive accumulation of radiopharmaceuticals, according to PET-CT. Clinicians should be highly suspicious of KFD in young patients with cervical lymphadenopathy and fever to avoid misdiagnosis.

Modern approaches to the diagnosis and treatment of cardiac sarcoidosis: results of a cohort study

Aim. To analyze clinical and paraclinical data in patients with documented cardiac sarcoidosis, outlining the key points of diagnosis and selection of the optimal treatment.Material and methods. For the period from 2016 to 2021, 63 patients (50,4±14,1 years) were included in the cohort study on negotiability. Based on a standard examination, 15 patients (41±13 years old) were selected, who continued the examination to confirm the diagnosis of cardiac sarcoidosis. Contrast-enhanced cardiac magnetic resonance imaging (MRI) was performed in 10 patients, while endomyocardial biopsy in 7 patients. All patients underwent 18F-fluorodeoxyglucose positron emission tomography (PET).Results. The most common (53%) electrocardiographic abnormality was right bundle branch block. Ventricular arrhythmias and high-grade atrioventricular block were recorded mainly in patients with documented activity. Regional contractility disorders were predominantly detected in patients with cardiac fibrosis. Delayed contrast enhancement according to cardiac MRI was recorded mainly intramurally in the interventricular septum and subepicardial area of left ventricular (LV) lateral wall. When analyzing the PET results, we found the predominant radiopharmaceutical accumulation in the interventricular septum (56%), lateral (44%) and anterior (33%) LV walls. There was no significant improvement in global LV contractility against the background of immunosuppressive therapy, especially in patients with reduced ejection fraction: initially 49,2±10,1% vs 46,9±14,9% during therapy (p=0,658).Conclusion. A certain apprehensive attitude of the doctor and adherence to the algorithm for early diagnosis of cardiac sarcoidosis allows minimizing the risks of fatal cardiovascular events. On the contrary, in the case of late diagnosis, even the use of aggressive immunosuppressive therapy does not lead to an improvement in global myocardial contractility, and fibrosis zones can cause life-threatening bradyarrhythmias and ventricular arrhythmias.

Artificial Intelligence of Object Detection in Skeletal Scintigraphy for Automatic Detection and Annotation of Bone Metastases.

When cancer has metastasized to bone, doctors must identify the site of the metastases for treatment. In radiation therapy, damage to healthy areas or missing areas requiring treatment should be avoided. Therefore, it is necessary to locate the precise bone metastasis area. The bone scan is a commonly applied diagnostic tool for this purpose. However, its accuracy is limited by the nonspecific character of radiopharmaceutical accumulation. The study evaluated object detection techniques to improve the efficacy of bone metastases detection on bone scans. We retrospectively examined the data of 920 patients, aged 23 to 95 years, who underwent bone scans between May 2009 and December 2019. The bone scan images were examined using an object detection algorithm. After reviewing the image reports written by physicians, nursing staff members annotated the bone metastasis sites as ground truths for training. Each set of bone scans contained anterior and posterior images with resolutions of 1024 × 256 pixels. The optimal dice similarity coefficient (DSC) in our study was 0.6640, which differs by 0.04 relative to the optimal DSC of different physicians (0.7040). Object detection can help physicians to efficiently notice bone metastases, decrease physician workload, and improve patient care.

Cardiac positron emission tomography in prediction of the clinical course of chronic thromboembolic pulmonary hypertension: prospective cohort study

INTRODUCTION: During the development of CTEPH maladaptive mechanisms in the right ventricle are accompanied by disturbances in myocardial energy metabolism and perfusion. These changes can be assessed visually and quantitatively using the molecular imaging method — PET with [18F]-FDG and [13N]-NH3.OBJECTIVE: Using cardiac PET/CT investigate the relationship between perfusion and metabolism of the right ventricular myocardium and the results of other instrumental examination methods in patients with CTEPH of different severity, as well as to calculate the threshold PET values to determine the group of patients with an unfavorable clinical course of the disease.MATERIALS AND METHODS: The study included 36 patients with a verified diagnosis of CTEPH, who were examined using a standard diagnostic protocol. Patients underwent cardiac PET/CT examinations with two radiopharmaceuticals: with [18F]-FDG to study the metabolism of the ventricular myocardium and with [13N]-NH3 to assess cardiac perfusion. For each radiopharmaceutical semi-quantitative accumulation indices (SUV) and the ratio of the levels of radiopharmaceutical uptake in the right and left ventricles (SUV RV/SUV LV) were obtained. Statistics: Shapiro-Wilk test, Student’s t-test, and Mann-Whitney U-test, Pearson correlation analysis, linear regression analysis, ROC analysis.RESULTS: The level of [18F]-FDG accumulation in the right ventricular myocardium is higher in patients with a high functional class of PH than in groups I, II (p&lt;0.01). All indicators of SUV RV/SUV LV for [18F]-FDG demonstrate a direct linear relation-ship with the level of mean PAP (r=0.691, p&lt;0.0001), PVR (r=0.715, p&lt;0.0001), right ventricular size (r=0.658, p&lt;0.0001), PASP (r=0.581, p&lt;0.001) and inverse linear relationship with the functional parameters of the right ventricle CI (r=–0.555, p=0.001), CO (r=–0.488, p=0.005), TAPSE (r=–0.552, p&lt;0.001), TAVS (r=–0.537, p&lt;0.001), and SvO2 (r=–0.666, p&lt;0.0001). A correlation was found between the accumulation of [13N]-NH3 and the main hemodynamic parameters used to assess the severity of the disease (СI, SvO2). The threshold values of [18F]-FDG and [13N]-NH3 accumulation indices have been obtained, which with high sensitivity (69.2–83.3%), specificity (68.4–94.7%) and diagnostic accuracy (0.73–0.83) make it possible to identify patients with a low cardiac index and an unfavorable prognosis.DISCUSSION: The obtained results confirm the presence of glucose hypermetabolism in right ventricular cardiomyocytes in the development of pulmonary hypertension and the association of these metabolic changes with the severity of PH. A significant correlation was demonstrated between the accumulation of both radiopharmaceuticals in the heart and the results of other examination methods characterizing the severity of disease and the prognosis of patients with CTEPH. Using a non-invasive PET/CT procedure, threshold values of PET parameters were obtained, which in the future can be used to identify patients with an unfavorable clinical prognosis.CONCLUSION: Cardiac PET/CT with [18F]-FDG and [13N]-NH3 is a promising non-invasive imaging technique that can be used to study metabolic and perfusion changes in the right ventricular myocardium in CTEPH, as well as to identify patients with a high risk of adverse events.

Radionuclide imaging of breast cancer: experience of FSBI “N.N. Petrov National Medical Research Centre of Oncology” of the Ministry of Healthcare of Russian Federation

Abstract. Breast cancer is one of the most common malignant neoplasms among women nowadays. Timely diagnosis is the basis for effective and successful treatment of this disease. The existing classical methods of X-ray examination (MG, ultrasound, MRI) play a major role in the detection of breast cancer, but in some cases, the diagnosis of breast cancer can be difficult. Therefore, diagnostic performance of scintimammography with specialized gamma camera called molecular breast imaging (MBI) is now of particular clinical interest.Materials and methods. 312 patients with a preliminary clinical diagnosis of breast cancer were examined in the department of radionuclide diagnostics of N.N. Petrov Research Center of Oncology. They underwent scintimammography (MBI) with a specialized gamma camera manufactured by GE (Discovery 750b). Images of both breasts were obtained 15 min after intravenous injection of 500 MBq activity of 99mTc-MIBI. The foci of moderate and intensive radiopharmaceutical accumulation in breast were considered as a sign of a tumor. The diagnostic performance of MBI and the sensitivity in detection of various biological subtypes of cancer were calculated by comparing with the results of morphological and immunohistochemically studies.Results. The sensitivity, specificity and accuracy of the MBI in the diagnostics of breast cancer were 88, 75 and 87%, respectively. Sensitivity of this method in detection of different biological subtypes ranged from 89% to 95% with lowest performance found in luminal A subtype.Conclusion. Scintimammography (MBI) is an informative way of breast cancer diagnostics. The revealed differences in the sensitivity of the method in patients with different biological subtypes of breast cancer confirm the need for further study of this topic.

High-Dose Brachytherapy in Chemoradiation Schemes of Patients &#x0D; with Oral Mucosa Cancer

The aim of the study was to improve clinical outcomes of oral mucosa cancer in case of surgical treatment failure.Materials and methods. A clinical case of combined radiation treatment of a patient with oral floor mucosa cancer St III T3N1M0 was presented. Pathogistological diagnosis # xxxxxx was: highly differentiated squamous cell carcinoma. A treatment plan was developed. Chemoradiotherapy at the first stage included 3 courses of intra-arterial chemotherapy (Selective (superselective) embolization (chemoembolization) of tumor vessels in the basin of the left and right facial and left lingual arteries, cisplatin 150 mg, combined with a daily infusion of 5-fluorouracil 4000 mg), with an interval 21 day. Chemoradiotherapy at the second stage included volume modulated arc therapy (VMAT) on the area of ​​the primary tumor (oral floor mucosa) and the regional metastasis pathways (total boost dose 60 Gy to the area of ​​regional lymph flow, otal boost dose 50 Gy to the oral cavity). Chemoradiotherapy at stage 3 included interstitial radiation therapy. A single boost dose (SBD) for the primary focus was 3 Gy/per fraction, 2 times a day, with an interval of 6 hours until total boost dose reached 21 Gy, 7 fractions.Results. After treatment, a complete regression of the tumor was noted. No pathological accumulation of radiopharmaceuticals, features of the tumor process was detected on PET/CT 48 months after treatment.Conclusions. Chemoradiotherapy combined with brachytherapy can be considered as an equal alternative to surgical treatment of patients with oral mucosa cancer.

In Vivo Preclinical Assessment of β-Amyloid-Affine [11C]C-PIB Accumulation in Aluminium-Induced Alzheimer's Disease-Resembling Hypercholesterinaemic Rat Model.

Aluminum (Al) excess and hypercholesterinaemia are established risks of Alzheimer's disease (AD). The aim of this study was to establish an AD-resembling hypercholesterinaemic animal model-with the involvement of 8 week and 48 week-old Fischer-344 rats-by Al administration for the safe and rapid verification of β-amyloid-targeted positron emission tomography (PET) radiopharmaceuticals. Measurement of lipid parameters and β-amyloid-affine [11C]C-Pittsburgh Compound B ([11C]C-PIB) PET examinations were performed. Compared with the control, the significantly elevated cholesterol and LDL levels of the rats receiving the cholesterol-rich diet support the development of hypercholesterinaemia (p ≤ 0.01). In the older cohort, a notably increased age-related radiopharmaceutical accumulation was registered compared to in the young (p ≤ 0.05; p ≤ 0.01). A monotherapy-induced slight elevation of mean standardised uptake values (SUVmean) was statistically not significant; however, adult rats administered a combined diet expressed remarkable SUVmean increment compared to the adult control (SUVmean: from 0.78 ± 0.16 to 1.99 ± 0.28). One and two months after restoration to normal diet, the cerebral [11C]C-PIB accumulation of AD-mimicking animals decreased by half and a third, respectively, to the baseline value. The proposed in vivo Al-induced AD-resembling animal system seems to be adequate for the understanding of AD neuropathology and future drug testing and radiopharmaceutical development.

Cross-reactivity to glutamate carboxypeptidase III causes undesired salivary gland and kidney uptake of PSMA-targeted small-molecule radionuclide therapeutics.

Recently, Pluvicto™ ([177Lu]Lu-PSMA-617), a small-molecule prostate-specific membrane antigen (PSMA) radioligand therapeutic, has been approved by the FDA in metastatic castration-resistant prostate cancer. Pluvicto™ and other PSMA-targeting radioligand therapeutics (RLTs) have shown side effects due to accumulation in certain healthy tissues, such as salivary glands and kidney. Until now, the molecular mechanism underlying the undesired accumulation of PSMA-targeting RLTs had not been elucidated. We compared the sequence of PSMA with the entire human proteome to identify proteins closely related to the target. We have identified glutamate carboxypeptidase III (GCPIII), N-acetylated alpha-linked acidic dipeptidase like 1 (NAALADL-1), and transferrin receptor 1 (TfR1) as extracellular targets with the highest similarity to PSMA. The affinity of compound 1 for PSMA, GCPIII, NAALADL-1, and TfR1 was measured by fluorescence polarization. The expression of the putative anti-target GCPIII was assessed by immunofluorescence on human salivary glands and kidney, using commercially available antibodies. A fluorescent derivative of Pluvicto™ (compound 1) bound tightly to PSMA and to GCPIII in fluorescence polarization experiments, while no interaction was observed with NAALADL-1 and TfR1. Immunofluorescence analysis revealed abundant expression of GCPIII both in healthy human kidney and salivary glands. We conclude that the membranous expression of GCPIII in kidney and salivary gland may be the underlying cause for unwanted accumulation of Pluvicto™ and other Glu-ureido PSMA radio pharmaceuticals in patients.