Current radiopharmaceuticals最新文献

Cardiovascular disorders are among the critical side effects of cancer therapy. Damage to the function and normal structure of the heart can cause serious threats to patients that are being treated for cancer. Cardiovascular complications may be induced by various types of chemotherapy drugs and also radiation therapy. The severity of cardiovascular toxicity depends on several factors, such as types of drugs, tumor location for radiotherapy, the presence of cardiac disease history, the dose of drugs or ionizing radiation, etc. Radiotherapy and chemotherapy can cause heart diseases through various mechanisms, such as oxidative stress, inflammation, cell death, fibrosis, endothelial to mesenchymal transition (EndMT), etc. Chronic inflammation following damage to a huge number of cells can trigger more accumulation of inflammatory cells and chronic release of reactive oxygen species (ROS) and nitric oxide (NO). Oxidative stress can induce more cell death and cardiac remodeling through damage to vessels and valvular and disruption of the normal structure of the extracellular matrix. These changes may lead to cardiomyopathy, myocarditis, pericarditis, and vascular disorders that may lead to heart attack and death. This review provides basic information on cellular and molecular mechanisms of different types of cardiovascular disorders following cancer therapy by radiation or chemotherapy. We also recommend some adjuvants and targets to reduce the risk of heart toxicity by radiation/chemotherapy.

Introduction: The feasibility of preparing the "in-house" generators and the Th- DTPA(DOTA)-Nimotuzumab radioimmunoconjugate was evaluated. ²²⁶Th is perspective for TAT, however, due to short half-life it is preferable to apply this radionuclide for readily available epithelial malignancies. Nimotuzumab being specific for EGFR expressing cells as a targeting moiety is considered to be suitable for thorium delivery.

Methods: TEVA extraction chromatographic resin and anion exchange resin AG 1x8 were used as sorbents for ²²⁶Th generator. In order to determine features of labeling by Th4⁺ we applied ²³⁴Th as a longer-lived analog of short-lived ²²⁶Th and the immunoconjugates DTPA(DOTA)-Nimotuzumab were used for radiolabeling.

Results: The generator on the base of TEVA resin has shown higher volume activity of the product compared to the AG 1x8. The ²²⁶Th volume concentration was up to 80%/mL. The radiolabeling of BFCA by thorium radioisotopes reached 95% at the MR(Th:p-SCN-Bn-DTPA) = 1:100 and 86% for MR(Th:p-SCN-Bn-DOTA) = 1:5000 at 90°C. The procedure of Nimotuzumab labeling with Th4+ for radiotherapy of EGFR-overexpressing carcinomas was established. The overall labeling yield in both radioimmunoconjugates - DTPA and DOTA functionalized - was in the range of 45-50%. The immunoconjugate Nimotuzumab-p-SCN-Bn-DTPA was obtained with a molar ratio 1:25 (Nimotuzumab: BFCA), within 1 hour of conjugation at 25°C and labelled via postconjugation approach. Whereas Nimotuzumab-p-SCN-Bn-DOTA was obtained at the same conditions, but radiolabeled by the method of pre-conjugation.

Conclusion: Thorium-234 incorporation into both radioimmunoconjugates reached 45-50%. It has been shown that Th-DTPA-Nimotuzumab radioimmunoconjugate specifically bound with EGFR overexpressing epidermoid carcinoma A431 cells.

Cancer treatment has the potential to cause cardiovascular issues and can encourage the appearance of all aspects of cardiac disease, including coronary heart disease, myocardial disease, heart failure, structural heart disease, and rhythm problems. Imaging is required for both diagnostic workup and therapy monitoring for all possible cardiovascular side effects of cancer therapy. Echocardiography is the cardiac imaging gold standard in cardio-oncology. Despite advancements in its use, this method is often not sensitive to early-stage or subclinical impairment. The use of molecular imaging technologies for diagnosing, assessing, and tracking cardiovascular illness as well as for treating, it is fast growing. Molecular imaging techniques using biologically targeted markers are gradually replacing the traditional anatomical or physiological approaches. They offer unique insight into patho-biological processes at the molecular and cellular levels and enable the evaluation and treatment of cardiovascular disease. This review paper will describe molecularbased single-photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging techniques that are now available and in development to assess post-infarction cardiac remodeling. These methods could be used to evaluate important biological processes such as inflammation, angiogenesis, and scar formation.

Background: The relation between micro-RNA (miRNA) modulation and immune cell activity in high-dose radiation settings is not clearly understood.

Objective: To investigate the role of stereotactic radiosurgery (SRS) in (i) the regulation of tumorsuppressor and oncogenic miRNAs as well as (ii) its effect on specific immune cell subsets in patients with metastatic brain tumors (MBT).

Methods: 9 MBT patients who underwent gamma knife-based stereotactic radiosurgery (GKRS) and 8 healthy individuals were included. Serum samples were isolated at three-time intervals (before GKRS, 1 hour, and 1-month post-GKRS). Expressions of tumor-suppressor (miR-124) and oncogenic (miR-21, miR-181a, miR-23a, miR-125b, and miR-17) miRNAs were quantified by qPCR. The lymphocytic frequency (CD3⁺, CD4⁺, CD8^+, CD56⁺, CD19⁺, and CD16⁺) was investigated by means of flow cytometry.

Results: The median age was 64 years (range: 50-73 years). The median prescription dose was 20Gy (range: 16Gy-24Gy), all delivered in a single fraction. The median overall survival and progression- free survival were 7.8 months (range: 1.7-14.9 months) and 6.7 months (range: 1.1-11.5 months), respectively. Compared to healthy controls, baseline levels of oncogenic miRNAs were significantly higher, while tumor-suppressing miRNA levels remained markedly lower in MBT patients prior to GKRS. Following GKRS, there was a reduction in the expression of miR-21, miR-17, and miR-181a; simultaneously, increased expression increased of miR-124 was observed. No significant difference in immune cell subsets was noted post GKRSIn a similar fashion. We noted no correlation between patient characteristics, radiosurgery data, miRNA expression, and immune cell frequency.

Conclusion: For this specific population with MBT disease, our data suggest that stereotactic radiosurgery may modulate the expression of circulating tumor-suppressor and oncogenic miRNAs, ultimately enhancing key anti-tumoral responses. Further evaluation with larger cohorts is warranted.

Aim: The aim of this study was to implement an in-house dosimetric tool to assess tumour- absorbed doses in pre and post-dosimetry for ⁹⁰Y radioembolization with resin spheres.

Materials and methods: To perform dosimetric calculations we set up a dosimetric procedure and developed homemade software to calculate tumour absorbed dose and dose volume histograms (DVHs). The method is based on a simplified voxel dosimetry for an estimated 3D absorbed dose and it can be applied to both ^99mTc-MAA SPECT/CT and ⁹⁰Y PET/CT acquisitions for pre and post-dosimetry. We tested the software performance in a retrospective study using the data of 22 patients with hepatocellular carcinoma who underwent radioembolization with ⁹⁰Y resin spheres in the period 2016-2021. The software calculates tumour doses (mean, minimum and maximum doses) from voxel counts and dose-volume histograms (DVH_spect, DVH_pet) for both ^99mTc-MAA SPECT/CT and ⁹⁰Y PET/CT imaging. DVH_spect and DVH_pet data were analyzed and compared with the aim to assess an agreement between them. Concordance between dosimetric data were evaluated with the Wilcoxon Signed Ranked test, descriptive statistical analysis and Pearson correlation coefficient.

Results: The mean administrated activity was 1313 MBq (range 444 MBq - 2200 MBq). Tumour volumes ranged from 75 mL to 1012 mL. The mean absorbed dose for tumour volume was 161 ± 66 Gy (Dm_spect) and 173 ± 79 Gy (Dm_pet). From Wilcoxon Signed Rank Test the differences between the dosimetric data extrapolated from DVH_spect and DVH_pet results were not significant with α = 0.05 (two-sided test). A good linear correlation was found between ^99mTc-MAA and ⁹⁰Y dosimetric data (Pearson correlation coefficient 0.887 p < 0.001). Generally, DVHs calculated on ^99mTc-MAA SPECT/CT and ⁹⁰Y PET/CT gave comparable results, some discrepancies were observed particularly with those patients where SPECT and PET imaging presented a visual mismatching.

Conclusion: A simplified 3D dosimetry methodology was implemented and tested retrospectively on patient data treated with ⁹⁰Y resin spheres. Even if the clinical feasibility of our approach has to be further validated on an extended patient cohort, the preliminary results of our study highlight the potential of the implemented dosimetric tool for tumour dose assessment.

Objective: Previously, low-dose radiation therapy was used for pneumonia treatment. We aimed to investigate the safety and effectiveness of carbon nanoparticles labeled with Technetium isotope (^99mTc) in a form of ultradispersed aerosol in combination with standard COVID-19 therapy. The study was a randomized phase 1 and phase 2 clinical trial of low-dose radionuclide inhalation therapy for patients with COVID-19 related pneumonia.

Methods: We enrolled 47 patients with confirmed COVID-19 infection and early laboratory signs of cytokine storm and randomized them into the Treatment and Control groups. We analyzed blood parameters reflecting the COVID-19 severity and inflammatory response.

Results: Low-dose ^99mTc-labeled inhalation showed a minimal accumulation of radionuclide in lungs in healthy volunteers. We observed no significant differences between the groups before treatment in WBC-count, D-dimer, CRP, Ferritin or LDH levels. We found that Ferritin and LDH levels significantly raised after the 7th day follow-up only in the Control group (p < 0.0001 and p = 0.0005, respectively), while mean values of the same indicators did not change in patients in the Treatment group after the radionuclide treatment. D-dimer values also lowered in the radionuclide treated group, however, this effect was not statistically significant. Furthermore, we observed a significant decrease in CD19+ cell counts in patients of the radionuclide-treated group.

Conclusion: Inhalation low-dose radionuclide therapy of ^99mTc aerosol affects the major prognostic indicators of COVID-19- related pneumonia restraining inflammatory response. Overall, we identified no evidence of major adverse events in the group receiving radionuclide.

Background: New generation PET/CT devices provide quality images using low radiopharmaceutical activities. Dose monitoring is carried out for nuclear medicine personnel, other health personnel, and companions by determining the radiation dose emitted from low-activity patients to the environment. In particular, it is necessary to revise the working conditions of the personnel according to the radiation dose exposed.

Aim: It was aimed to reevaluate the radiation dose rate transmitted to the environment from patients injected with ¹⁸F-FDG.

Materials and methods: A total of 31 patients (14F, 17M) who underwent ¹⁸F-FDG PET/CT imaging were included. The mean ¹⁸F-FDG activity of 7.26 ± 1.29 mCi was used for injection. After injection, radiation dose rates (mR/h) were measured at distances of 25, 50, 100, 150, and 200cm for 3 different periods from the level of the head, thorax, abdomen, and pelvis by using a GM counter. Additionally, biological samples such as urine and sweat were taken during 3 different periods. The activity amounts (μCi) in the samples were measured with a well-type counter.

Results: Strong correlations were calculated between normalized dose rates obtained by all regions and time. Considering the nuclear medicine staff handling time with a PET/CT patient, the average dose received by staff was calculated between a range of 0.002-0.004 mSv/pt. The radiation dose exposed to the porter and nurse was calculated as 0.049 mSv/pt for the 2^nd hour and 0.001-0.007 mSv/pt for the 4^th hour, respectively. The companion was exposed to a dose between 0.073-0.147 mSv and 0.024-0.048 mSv for public transport and private car transportation after 4-6 hours of injection (for 30-60 min of travel duration), respectively. For inpatients, the received dose for porters, serving 20min from a distance of 30cm for the 2^nd and 4^th hours after the PET/CT scan, was 0.049 mSv/pt and 0.048 mSv/pt, respectively. And for nurses serving from a 50cm distance between 1-5 minutes, these values were found to be 0.001-0.007mSv/pt, 0.001-0.007mSv/pt, and 0.001-0.006mSv/pt, respectively.

Conclusion: The radiation dose of nuclear medicine staff, porters, nurses, and companions are found to be below the recommended dose limit by the ICRP. According to our results, there is no need for any restrictions for patients, companions, or healthcare personnel in PET/CT units.

Angiogenesis phenomenon, as a highly affecting factor on the growth and spread of cancer cells, depends on specific molecular interactions between components of the extracellular matrix and vascular cells. αv integrin acts as a cell adhesive molecule involved in tumor invasion and angiogenesis. Among the various combinations of integrin subunits expressed on the surface of cells, α_vβ₃ integrin has a particularly interesting expression pattern during angiogenesis. The α_vβ₃ integrin is a vital receptor affecting tumor growth, tumor invasiveness, metastasis, and angiogenesis overexpressed on various human tumors, leading to the development of different theranostics probes and radiopharmaceuticals. The α_vβ₃ integrin can recognize several extracellular matrix molecules in the base of the RGD adhesive sequence. This review provides an overview of the status, trends and future of the most studied α_vβ₃ integrin-binding ligand, RGD tripeptides, labeled with various radioisotopes. An overview of the pre-clinical models for radiolabeled RGD peptides and clinical aspects of the RGD- based radiopharmaceuticals is provided with some new considerations and ways forward.

Background: Despite substantial research, the mechanisms behind stress Tako-tsubo cardiomyopathy (TTC) remain rather elusive.

Objective: The purpose of this paper was to provide a detailed review of the mainstream factors underlying the pathophysiology of TTC, highlighting the novel contributions of molecular pathology and in-vivo molecular imaging.

Methods: A careful literature review selected all papers discussing TTC, specifically those providing novel insights from myocardial pathology and cardiac molecular imaging.

Results: Results concerning myocardial pathology, defect extension, sites and relationships between functional parameters underline the existence of a causal relationship between a determinant (e.g., the release of catecholamines induced by stress) and an outcome for TTC, which is not limited to a reversible contractile cardiomyopathy, but it includes reversible changes in myocardial perfusion and a long-lasting residual deficit in sympathetic function. Besides, they reinforce the hypothesis that sympathetic nerves may exert a complex control on cardiac contractile function, which is likely to be direct or indirect through metabolism and microvascular perfusion changes during anaerobic and aerobic conditions.

Conclusion: TTC is characterized by acute transient left ventricular systolic dysfunction, which can be challenging to distinguish from myocardial infarction at presentation. Catecholamineinduced myocardial injury is the most established theory, but other factors, including myocardial metabolism and perfusion, should be considered of utmost importance. Each effort to clarify the numerous pathways and emerging abnormalities may provide novel approaches to treat the acute episode, avoid recurrences, and prevent major adverse cardiovascular events.