This minireview describes the global situation of ongoing research and development and the clinical application of alpha emitter labeled immunoconjugates with various alpha emitters with an overview of the future trends. The potentially helpful alpha emitter radioisotopes for medical applications, chelators, and immunomolecules of interest for future alpha radioimmunotherapy are discussed. Challenges and some suggested future works on chelators are also presented.
Introduction: With its suitable nuclear decay characteristics and large-scale production feasibility with adequate specific activity, 177Lu is regarded as an excellent radionuclide for developing bone pain palliation agent. Ethylenediamine-tetramethylene phosphonic acid (EDTMP) is a preferred carrier molecule for radiolanthanides, such as 177Lu. The present paper describes the synthesis of EDTMP and the development of a ready-to-use kit for the preparation of 177Lu-EDTMP and its quality control in accordance with the quality and safety criteria required for medicinal use.
Material and methods: EDTMP was synthesized by a modified Mannich-type reaction, and the structure was characterized using NMR and IR spectroscopy. Optimization of radiolabeling conditions was done with two different salt forms of EDTMP. The labeling yield was checked by paper chromatography with radiation detection. Kit was developed as a lyophilized mixture of EDTMP and sodium bicarbonate in a maximum volume of 5 mL. Labeling efficiency, radionuclidic purity, radiochemical purity, sterility, and pyrogenicity analysis were performed as the quality control of the labeled kit.
Results: The analytical data for the structure determination and purity of the synthesized ligand were in agreement with authentic commercial samples used in radiopharmacy.177Lu-EDTMP complex was prepared using synthesized EDTMP ligand under optimized labeling conditions with high labelling yield (>99%). The radiolabeling yields of the EDTMP kit at room temperature after 30 min and 48 hours were 99.46% and 99.00%.
Conclusion: The developed EDTMP kit enables an instant one-step preparation of the radiopharmaceutical of high radiochemical purity (>99%) and has a sufficiently long shelf life. This enables the routine production of the 177Lu-EDTMP in nuclear medicine clinics without requiring experienced staff.
Background: Bone metastatic involvement represents a leading cause of death in patients with advanced breast cancer (BC). At present, it is not clear whether the bone metastatic load might impact Overall Survival (OS) in patients with bone metastatic BC at diagnosis. For this purpose, we used the Bone Scan Index (BSI), which is a reproducible and quantitative expression of tumor load observed at bone scintigraphy.
Objective: The aim of this study was to associate BSI with OS in bone metastatic BC patients.
Methods: In this retrospective study, we enrolled BC patients with bone metastases at the scintigraphic bone scan performed for staging purposes. The BSI was calculated through the DASciS software, and statistical analysis was carried out. Other clinical variables relevant to OS analysis were taken into account.
Results: Of a total of 94 patients, 32% died. In most cases, the histotype was ductal infiltrating carcinoma. The median OS from diagnosis was 72 months (CI 95%: 62-NA). The univariate analysis with COX regression showed that only hormone therapy significantly correlates with OS (HR 0.417, CI 95%: 0.174-0.997, p < 0.049). As concerning BSI, the statistical analysis showed that it does not predict OS in BC patients (HR 0.960, 95% CI: 0.416-2.216, p < 0.924).
Conclusion: Although the BSI significantly predicts OS in prostate cancer and in other tumors, we observed that the metastatic load of bone disease has not a key role in prognostic stratification in our population.
Introduction: Hypoxia imaging agents can selectively remain in hypoxic tissue, which can directly reflect the location and degree of hypoxia.
Methods: Synthesized a novel tumor hypoxia imaging probe [99mTc]Tc(CO)3-CPA-2-NIM and evaluated its biological behavior with the purpose to assess its possibility of becoming a qualified tumor hypoxia imaging agent.
Results: Radiochemcial purity of [99mTc]Tc(CO)3-CPA-2-NIM was greater than 95% after HPLC purification. Lipophilicity coefficient of this complex was -1.74 ± 0.10 (n = 5, number of experiments), indicating it was a hydrophilic complex. In vitro cell experiments demonstrated that this complex has selectivity for hypoxia at oxygen concentrations < 10 ppm (parts per million). Biodistribution experiment in S180 tumor bearing mice showed that tumor uptake reached its highest at 2 h post-injection with mice tumor-to-muscle ratio.
Conclusions: Complex [99mTc]Tc(CO)3-CPA-2-NIM has the possibility of becoming a tumor hypoxia imaging agent.
Background: Transarterial Radioembolization (TARE) is a widespread radiation therapy for unresectable hepatic lesions, but a clear understanding of the dose-response link is still missing. The aim of this preliminary study is to investigate the role of both dosimetric and clinical parameters as classifiers or predictors of response and survival for TARE in hepatic tumors and to present possible response cut-off.
Methods: 20 patients treated with glass or resin microspheres according to a personalized workflow were included. Dosimetric parameters were extracted from personalized absorbed dose maps obtained from the convolution of 90Y PET images with 90Y voxel S-values.
Results: D95 ≥ 104 Gy and tumor mean absorbed dose MADt ≥ 229 Gy were found to be optimal cut-off values for complete response, while D30 ≥ 180 Gy and MADt ≥ 117 Gy were selected as cut-off values for at least partial response and predicted better survival. Clinical parameters Alanine Transaminase (ALT) and Model for End-Stage Liver Disease (MELD) didn't show sufficient classification capability for response or survival.
Concusion: These preliminary results highlight the importance of an accurate dosimetric evaluation and suggest a cautious approach when considering clinical indicators. Dosimetric cut-off values could be a support tool in both planning and post-treatment phases. Larger multi-centric randomized trials, with standardized methods regarding patient selection, response criteria, Regions of Interest definition, dosimetric approach and activity planning are needed to confirm these promising results.
Nanotechnology has changed the world, with a great impact on industry and medicine. In this commentary, we discuss the importance of radiolabeled nanomaterials for the construction of theranostic, imaging and therapeutic agents in order to pave the future of medicine.
Background: Some compounds have been investigated to mitigate the effect of radiation on the lung, such as pneumonitis and fibrosis.
Objective: This study aimed to examine the mitigation efficiency of Spirulina compared to the effect of Metformin.
Methods: 25 male Wistar rats were allotted in five groups: control, Spirulina, Radiation, Radiation plus Spirulina, and Radiation plus Metformin. Rat chest regions were irradiated by 15 Gray (Gy) xradiation using aLINAC. Forty-eight hours after irradiation, treatment with Spirulina and Metformin began. Eighty days after irradiation, all rats were sacrificed, and their lung tissues were removed for histopathological, and biochemical assays.
Results: The results demonstrated that irradiation increased MDA (Malondialdehyde) levels while suppressing the SOD (superoxide dismutase) and GPx(glutathione peroxidase) activity in the irradiated group. MDA levels in lung tissues were reduced with Metformin but not with Spirulina. Both Metformin and Spirulina increased the SOD and GPx activity in lung tissue. Moreover, histopathological evaluations showed extensive changes in the lung tissue including infiltration of lymph cells around the bronchioles and blood vessels, thickening of the alveolar wall, and the disruption of the alveolar structure, as well as accumulation of collagen fibers. Administration of Spirulina and Metformin significantly reduced pathological changes in lung tissue, although the effect of Metformin was greater than that of Spirulina.
Conclusion: Spirulina could mitigate radiation-induced lung injury moderately, although Metformin is more effective than Spirulina as a mitigator agent.
Aims: We aim to reveal an effect of residual activity leftover within the medical materials other than the empty syringe used for injection of the tracer on SUV measurements and consequently effect on possible treatment response assessment.
Background: Staging and follow-up of pediatric lymphoma patients mainly achieved by the help of PET/CT scans. It is crucial to make an optimal imaging technique for interpreting individual images and assessing treatment response.
Objective: Standardized uptake value measurement is an important quantification parameter in PET/CT scanning of childhood lymphomas. Low dose of activity used in pediatric oncology patients makes them vulnerable to small changes of input values for subsequent metabolic parameters.
Methods: Sixty-eight pediatric lymphoma patients below 50 kg were included into the study. SUVmax, SUVpeak values of the most metabolically active lesions, along with liver and mediastinum, were recorded. Metabolic parameters of the lesions/lymph nodes, mediastinum and liver parenchyma were compared before and after counts from medical materials other than empty syringe were taken into account. Wilcoxon signed-rank test was used for non-parametric paired sampled tests for the groups.
Results: There were statistically significant differences between the whole 6 above-mentioned groups confirming the importance of residual counts on metabolic parameters (p < 0.001).
Conclusion: Our study demonstrated residual radioactivity in medical materials such as serum line tubes, i.v. catheters, three-way stopcock and also butterfly needles used during intravenous injection should also be included for optimum quantitative metabolic parameter values and to minimize its the adverse effect on treatment response evaluation, especially in borderline lesions.
Radiation treatment has been advancing ever since the discovery of X-rays in 1895. The goal of radiotherapy is to shape the best isodose on the tumor volume while preserving normal tissues. There are three advantages: patient cure, organ preservation, and cost-effectiveness. Randomized trials in many various forms of cancer (including breast, prostate, and rectum) with a high degree of scientific proof confirmed radiotherapy's effectiveness and tolerance. Such accomplishments, critical to patients' quality of life, have been supported in the past. Radiopharmaceuticals were developed to diagnose and treat various disorders, including hyperthyroidism, bone discomfort, cancer of the thyroid gland, and other conditions like metastases, renal failure, and myocardial infarction and cerebral infarction perfusion. It is also possible to sterilize thermo-labile materials with a radioactive substance. This includes surgical dressings and a wide range of other medical supplies. Nuclear medicine provides various advantages, including tumor localization, safe diagnosis, no radiation buildup, and excellent treatment effectiveness. Nowadays, the field of nuclear pharmacy is focused on developing novel radioactive pharmaceutical substances that will be useful.
Background: Chlorins (dihydroporphyrins) are tetrapyrrole-based compounds that are more effective in photodynamic therapy than porphyrins. The instability of the compounds and their oxidation to porphyrin limits the use of these compounds. However, the design and synthesis of new stable chlorin-based cationic photosensitizers with the potential for use in cancer photodynamic therapy can be interesting.
Methods: In this research, new tetracationic meso substituted chlorins were designed, synthesized, and characterized. After determining the chemical structure and spectroscopic properties of five new photosensitizers, their phototoxicity on breast cancer cell lines (MCF-7) was investigated under optimized conditions in terms of factors such as photosensitizer concentrations and light intensity.
Results: The results of cytotoxicity assayed by the MTT method showed that the synthesized compounds, even up to the concentration of 50 μM had very low toxicity in the absence of light, which indicates their safety under dark conditions. Compounds A1 and A3 with the best physicochemical properties such as solubility, high absorption intensity in the effective range of photodynamic therapy, and the high quantum yield of singlet oxygen, had a good toxic effect (IC50 = 0.5 μM) on the cancer cells (MCF-7) in the presence of laser light.
Conclusion: According to the obtained results, compounds A1 and A3 have the potential to continue research on PDT for confirmation and use in treatment.
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