Radiology & Imaging
RNA Binding Proteins are Pivotal Regulators of Cancer Radioresistance and Potential Targets for Preventing Tumor Recurrence
RNA-binding proteins (RBPs) regulate gene expression at the post-transcriptional level and are important factors in cancer progression and response to various therapeutic strategies. Radioresistance an obstacle caused due to various intrinsic and extrinsic factors remains a major hindrance in the treatment of cancer and could lead to tumor recurrence. Though research is being conducted on the cause and association of radioresistance with various cellular and environmental factors there remains much to be explored and discovered. The roles of several RNA-binding proteins in tumor progression and metastasis are well documented. In addition recent studies suggest the connection between Cancer Stem Cells (CSCs) and chemoresistance. We and others have extensively studied the regulatory role of RBPs in regulating CSCs. Resistance to radiation therapy and the involvement of RBPs in this process is under-studied. In this review we have provided an updated compilation of the significant role played by RBPs in radioresistance.
[68Ga]Ga-DOTA-TOC Synthesis by a Cassette Developer System with [68Ga]GaCl3 from Cyclotron using Liquid Target: An Italian Experience
[68Ga-DOTA-D-Phe1-Tyr3]octreotide ([68Ga]Ga-DOTA-TOC) is a somatostatin analogue largely used in PET/CT applications for the detection of gastroenteropancreatic neuroendocrine tumors (GEP-NET). Initially it was obtained using a 68Ge/68Ga generator. The increasing cost of good manufacturing practice-compliant generators has led to the need to find alternative ways of producing Gallium-68 (68Ga). The aim of this work is to show the production optimization of [68Ga]Ga-DOTA-TOC via cyclotron derived from three years of experience.
The production of [68Ga]GaCl3 via the 68Zn(pn)68Ga reaction was optimized using a PETtrace 800 cyclotron (equipped with ZnO liquid target) and the synthesis of [68Ga]Ga-DOTA-TOC was performed by FASTlab2 developer system according to the Guidelines on Good Radiopharmacy Practice (cGRPP). Quality control process was validated according to the current specific monograph (2482) of the European Pharmacopoeia (Ph. Eur.).
[68Ga]Ga-DOTA-TOC was produced in 40 minutes; ten validation batches met the quality criteria expected by the Ph. Eur. The synthesis process has involved many issues due to the use of acidic reagents and related corrosion of some components of cyclotron and developer system resulting in 12.2% failed syntheses and a target breakdown after 11 months.
The main issues their causes and the strategies used to solve them are reported in the troubleshooting section: thanks to these strategies the number of failed syntheses has decreased and today we have achieved a 0% failure rate.
Liquid target production of [68Ga]Ga-DOTA-TOC once consolidated instead of 68Ge/68Ga generator has many advantages.
Role of the p53/miR-34a/SIRT1 Feedback Loop in Metformin-induced Radiosensitivity of Colorectal Cancer Cells
Metformin induces radiation sensitivity in cancer cells including colorectal cancer cells; however the exact molecular mechanisms underlying its radiosensitive effects are not yet known. In this study we investigated the role of the p53/miR-34a/SIRT1 pathway in the radiosensitivity of colon cancer cells.
The study was carried out from 2020 to 2022 at the Qazvin University of Medical Science's Cellular and Molecular Research Center. Two colorectal cancer cell lines (SW480 and SW620) obtained from primary and secondary tumors derived from a single patient were used as the study samples. After subjecting the cells to 50 Gy of radiation we generated radioresistant cell lines. Resistant cells were treated with 50 µM metformin. Metformin-treated and untreated resistant cells constituted the study groups. The expression levels of miR-34-a and Sirtunin1 (SIRT1) were evaluated using Quantitative Real-time PCR. The rates of cell proliferation and apoptosis were assessed using a Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Western blot analysis was performed to quantify the expression of proteins. For statistical analysis the Student's t-test was carried out to examine the mean differences between the two groups and analysis of variance (ANOVA) was used to examine additional groups.
Our results showed that the expression of miR-34-a was downregulated (0.29 ± 0.11) in radiation-resistant cancer cells (P <0.001) while the expression of SIRT-1 was upregulated (4.5 ± 0.25) (P <0.001). Metformin increased the radiosensitivity of colon cancer cells in a time- and dose-dependent manner. Treatment with 50 µM metformin after 48h caused decreased cell viability and increased apoptosis in resistant cells. We observed downregulation of SIRT-1 (1.1 ± 0.45) and upregulation of miR-34-a (4.3 ± 1.3) (P <0.001) in metformin-treated cells. In contrast western blotting results showed the upregulation of acetylated P53 in metformin-treated cells. Metformin function was reversed by SIRT1 inhibitors or by transfection with miR-34-a overexpressing plasmids.
Based on these results one of the radiosensitivity mechanisms of metformin in colorectal cancer is the modulation of the p53/miR-34a/SIRT1 loop.
Nuclear Nanomedicines: Utilization of Radiolabelling Strategies, Drug Formulation, Delivery, and Regulatory Aspects for Disease Management
By integrating the sensitivity of nuclear medicine and the precision of nanotechnology mankind can explore the very promising nuclear nanomedicine technology. Such integration enabled the imaging of biological processes at the molecular level which is a blessing to modern disease management. The present work is an effort to highlight the multifaceted applications of radiolabelled nanomaterials across various imaging modalities formulation assessment drug development regulatory considerations and therapeutic interventions. The present work highlights the application of radiolabelled nanomaterials for molecular imaging. The single-photon emission computed tomography (SPECT) positron emission tomography (PET); and hybrid multimodalities along with their key features are inherent parts of this discussion. The discussion continues with the assessment procedures of new formulations and their implications for drug delivery and the associated regulatory affairs. Cell tracking strategies that allow real-time monitoring of cellular behaviour in vivo; and radionuclide therapy with targeted and precise treatment are explained with the comparison of different strategies. This is followed by the explanation of how the drug delivery systems incorporating molecular imaging radiotracers enable tracking of in vivo drug behavior further facilitating optimization of dosage forms and therapeutic efficacy. Thus this manuscript provides a comprehensive overview of the utilization of radiolabelling strategies across the spectrum of drug formulation delivery and regulatory aspects which is a way forward to future projections in nuclear nanomedicine. In conclusion the emergence of nuclear nanomedicines is a disease management breakthrough in modern healthcare systems. This innovative approach not only provides tailored diagnostics but also offers innovative therapeutic solutions.
Synergistic Potential of GLP-1 Receptor Agonists and Radiotherapy in Breast Cancer Treatment: A New Therapeutic Avenue (TROD-GROG 006)
GLP-1 receptor agonists (GLP-1 RAs) are anti-diabetic agents known for their anti-inflammatory and antioxidant properties. This study investigates the synergistic effects of GLP-1 RAs and radiotherapy (RT) on breast cancer in a preclinical mouse model.
Female BALB/c mice were inoculated with 4T1 breast cancer cells and divided into five groups: control placebo GLP-1 RA alone RT alone and combination treatment. GLP-1 RA was administered intraperitoneally and a single 8 Gy RT dose was applied. Tumor volumes histopathological changes cytokine expression and apoptosis-related protein profiles were evaluated. In vitro 4T1 cell viability was assessed following GLP-1 RA and/or RT exposure.
Combination therapy significantly reduced tumor volume compared to RT or GLP-1 RA alone. Histological analysis revealed improved tissue morphology with the combined approach. Immunohistochemical staining showed decreased expression of pro-inflammatory markers (IL-6 TNF-α) and angiogenic factors (VEGF-A FGF-2) while pro-apoptotic proteins (caspase-3 BAD p53) were elevated. In vitro findings confirmed a synergistic reduction in cell viability with combined treatment.
The results indicate that GLP-1 RAs potentiate the antitumor effect of RT in breast cancer primarily through modulation of apoptosis and the tumor microenvironment.
GLP-1 RAs may be effective adjuvants to RT in breast cancer particularly for patients with diabetes. The dual benefit of tumor sensitization and protection of normal tissues offers a promising therapeutic avenue.
Evaluating the Effectiveness of Geant4 Software in Measuring the Damage Caused by Ti48 Ion Radiation on Nerve Cells, in Comparison to the Biophysical Model and Empirical Data
Presently heavy particle ion radiation therapy is commonly utilized for the treatment of deep-seated malignancies such as brain tumors. In addition to tumor treatment these particles may negatively impact healthy nerve cells. Therefore it is essential to investigate the radiobiological effects of these radiations on cells. Simulation studies that model the radiation of heavy particles and the exact geometrical configuration of nerve cells are essential and effective in evaluating potential cellular damage.
The NEURON software was employed in Geant4 code to simulate an individual nerve cell (ID no: NMO 06176) and a network of ten neural cells subjected to bombardment by Ti48 ion particles at an energy of 600 MeV/u.
The absorbed energy differs among several components of individual cells and neural networks including the soma and dendrites. The absorbed doses from Ti48 radiation in individual nerve cells and dendritic networks surpass those in the cell body and this ratio remains consistent as the dosage escalates. The decrease in the initial length of dendrites in both individual cells and neuronal networks intensifies with increased dosages.
The simulation results demonstrate that dendrites absorb a higher radiation dose than the soma resulting in greater structural damage. This finding highlights the vulnerability of neuronal networks to high-LET radiation with important implications for space radiation protection and clinical radiotherapy planning.
The diminution of dendritic length due to Ti48 radiation is more significant within the cellular network compared to isolated nerve cells.
Dilemma on Pancreatic Uncinate Process Uptake on Ga68-DOTA Peptide PET/CT in Pediatric Neuroblastoma: Physiologic or Metastases?
The Ga68-DOTATATE PET/CT scan is an alternative imaging modality for the follow-up of children with neuroblastoma when the I123-MIBG scan was negative or weak. Somatostatin receptors (SSR) can be expressed in neuroblastoma lesions and when this happens targeting these receptors may be a good alternative to treating this disease in addition to conventional treatments. Our aim is to focus on the interpretation of one of the physiological tracer uptake sites the uncinate process of the pancreas using DW-MRI scans.
We present and discuss 4 cases with neuroblastoma for a technical note. Imaging scans for SSR were performed using Ga68-DOTATATE PET/CT and all showed varying degrees of increased uptake at the uncinate process of the pancreas on PET/CT images. We also performed a DW-MRI study to distinguish physiologic uptake in this region of the pancreas from metastatic involvement.
Two of them showed diffusion restriction with one of them also showing multiple masses within the liver. The other 2 children with high pancreatic uncinate process uptake did not exhibit any findings that indicated pancreatic involvement in the disease based on DW-MRI images and clinical findings.
We recommend comparing DW-MRI scans and SSR-PET/CT scans to determine the true state of physiologically elevated SSR concentration and consequently indicate increased uptake on the images. The radiotracer concentration at the high uptake site did not appear to correlate with malignant involvement of the organ. The higher number of patients may allow a statistical comparison of the tracer with malignancy status.
Real-world Data on Intermediate-risk Differentiated Thyroid Cancer Biochemical Response to 3700 or 5550 MBq of [131I]Sodium Iodide
The ideal [131I]Sodium Iodide activity for intermediate-risk thyroid cancer treatment is still uncertain. The objective of this study is to compare the biochemical responses to radioiodine therapy (RIT) of intermediate-risk thyroid cancer patients administered [131I]Sodium Iodide at doses of 3700 MBq (100 mCi) and 5550 MBq (150 mCi).
A retrospective study was conducted by reviewing the medical records of intermediate-risk thyroid cancer patients who received RIT between 2016 and 2020 at a reference cancer hospital in Brazil. Sociodemographic and clinical data were evaluated at the time of diagnosis. Clinical data during two years of follow-up were reviewed and biochemical responses were determined according to the American Thyroid Association (ATA 2015 version). Responses to doses of 3700 MBq (100 mCi) and 5550 MBq (150 mCi) of [131I]Sodium Iodide were compared.
No significant statistical differences were observed concerning the biochemical therapeutic responses of patients treated with 3700 MBq or 5550 MBq (p = 0.088). The presence of nodal metastasis and positive pre-RIT thyroglobulin did not influence biochemical responses to radioiodine.
According to ATA 2015 guidelines RIT may be administered to patients classified at intermediate risk for the ablation of post-surgical tissue remnants as well as an adjuvant treatment for potential persistent tumor foci and to reduce recurrence risks. These recommendations however do not specify the appropriate radioiodine dosage and this has been a topic of extensive debate.
Intermediate risk thyroid-cancer patients presented similar therapeutic responses to the doses of 3700 MBq and 5550 MBq [131I]Sodium Iodide.
The Central Composite Design and Artificial Neural Network Coupled with Genetic Algorithm in Optimization and Modeling of the Radiolabeling Process of 177Lu-hydroxyapatite as a Potential Radiosynovectomy Agent
A promising material used in radiation synovectomy of small joints is hydroxyapatite labeled with 177Lu. During the design and production of radiopharmaceuticals the condition of the radiolabeling process directly influences the radiochemical yield and consequently the quality of the final product so this process necessitates precise optimization.
In this investigation a central composite design based on response surface methodology and artificial neural networks modeling coupled with genetic algorithm technique is applied to build predictive models and explore key parameters' effect in hydroxyapatite's radiolabeling process with 177Lu radionuclide. The variables that directly affected the labeling reaction were the initial 177Lu radioactivity pH radiolabeling reaction time and temperature.
Based on the validation data set the statistical values demonstrate that the artificial neural networks model performs better than the response surface methodology model. The artificial neural networks model has a small mean squared error (9.08 artificial neural networks < 12.36 response surface methodology) and a high coefficient of determination (R2: 0.99 artificial neural networks > 0.93 response surface methodology). The optimum conditions to achieve maximum radiochemical yield based on response surface methodology using artificial neural networks modeling coupled with genetic algorithm were at the initial radioactivity of 177Lu radionuclide = 0.082 Gigabecquerel (GBq) pH = 6.75 time= 22 (min) and temperature = 37.8 (℃).
The ability to generate more data with fewer experiments for optimization and improved production is a pertinent advantage of multivariate optimization methods over traditional methods in radiation-related activities. The central composite design and artificial neural network-genetic algorithm optimization approaches are successfully utilized to create prediction models and investigate the impact of critical variables in the radiolabeling of hydroxyapatite with 177Lu radionuclide.
A New Approach to Synthesize Carbon-11-PBR28 and its Clinical Validation in ALS Patients
Many studies have reported translocator protein (TSPO) overexpression in various neurological disorders. Carbon-11[11C]PBR28 is a widely used TSPO Positron Emission Tomography (PET) radiopharmaceutical. We compared HPLC-based purification with cartridge-based purification and performed PET-MR imaging in ALS patients.
[11C]PBR28 was synthesized using both an HPLC-based and cartridge-based purification technique on the FX2C chemistry module. We injected 350 ± 20 MBq of the [11C]PBR28 intravenously into the patients diagnosed with amyotrophic lateral syndrome (ALS) limb onset (n =3) and bulbar (n =3). Simultaneous PET-MR dynamic imaging was then performed.
The radiochemical purity exceeded 95% with both methods. Using the HPLC-based method the radiochemical yield was 11.8 ± 3.3% molar activity was 253 ± 20.9 GBq/μmol and the total synthesis time of 25 ± 2 minutes. In contrast the cartridge-based method yielded a radiochemical yield of 53.0 ± 3.6% a molar activity of 885 ± 17.7 GBq/μmol and a total synthesis time of 12 ± 2 minutes. In imaging results higher activity was observed in the precentral gyrus and cerebellum at 2.5 ± 0.5 minutes in bulbar-onset ALS cases with a standardized uptake value (SUV) of 2.3 ± 0.3. In contrast limb-onset ALS cases showed the highest uptake at 0.5 ± 0.2 minutes with an SUV of 1.5 ± 0.2.
The difference in SUV in bulbar and limb onset may be due to pathological changes.
The cartridge-based purification method provided higher radiochemical yield and molar activity as compared to the HPLC purification method.
The Estimation Value of 99mTc-MAA in Comparison with 90Y-PET/MR-based Dosimetry in Selective Internal Radiation Therapy (SIRT) for Liver Malignancies
This study intended to compare the radiation dose estimates to target and non-target liver compartments from 99mTc-MAA SPECT/CT and 90Y-PET/MR scans in liver tumors treated by 90Y-glass microspheres.
Dose estimation was performed for twenty-three eligible patients (13M 10F) after 99mTc-MAA simulation using SPECT/CT imaging and over 90Y-PET/MR images after 90Y-microsphere therapy. Simplicit90Y™ software was used for voxel-based dosimetry over the liver parenchyma. Dose estimates were obtained for whole healthy liver (HL) healthy injected liver (HIL) and tumor volumes. Pearson correlation Bland–Altman plot and Wilcoxon signed-ranks test were used for statistical analysis.
The mean tumor dose was 270 ± 111 Gy the whole liver parenchyma dose was 26 ± 12 Gy and the healthy injected liver dose was 55 ± 18 Gy from 99mTc-MAA simulation. 90Y-PET/MR dosimetry yielded a mean tumor dose of 271 ± 125 Gy a HIL mean dose of 54±18 Gy and a liver parenchyma dose of 25 ± 12 Gy. An excellent agreement was demonstrated between tumor doses (R2=0.90) and liver doses (R2=0.87) while the agreement was less for HIL doses (R2=0.80). Wilcoxon signed-ranks test yielded no significant difference between the dose estimates for all liver compartments.
It was deduced that 99mTc-MAA SPECT/CT simulation provides valuable dose prediction in 90Y-glass microsphere therapy. Despite the difference in volume measurements and dose estimates with 90Y-PET/MR the predictive value of the 99mTc-MAA simulation was not affected.
Harnessing Radionuclides: Unveiling the Promising Role of Radiopharmaceuticals in Cancer Theranostics and Palliative Care
In the context of modern oncology radiogenic elements have emerged as pivotal tools for targeted cancer therapies. Elements like Iodine-131 and Yttrium-90 offer unique radiological properties that allow precise treatment delivery. This article explores their growing importance and potential in reshaping the landscape of cancer therapy.
Utilizing a systematic literature search relevant studies clinical trials and research articles were collected from databases. The selected material was scrutinized to extract insights into the mechanisms applications advantages and challenges of radiogenic elements. These results are combined in the study to give a perceptive picture of how contemporary oncology treatment is developing.
The article reveals a comprehensive analysis of the outcomes derived from the study of radiogenic elements in contemporary cancer treatment. The results highlight the diverse applications of radionuclides like Iodine-131 Yttrium-90 and actinides in targeted therapies. It showcases their ability to selectively damage cancer cells while sparing healthy tissues emphasizing precision and efficacy. The review underscores the increasing importance of personalized medicine combination therapies and the potential of emerging alpha-particle-based treatments. Furthermore the results shed light on the challenges posed by radiation safety and potential side effects prompting a need for vigilant management. This comprehensive examination of results provides a nuanced understanding of the pivotal role that radiogenic elements play in shaping the future of modern oncology therapy.
The article examines the role of radiogenic elements in contemporary cancer treatment. It highlights the significance of elements like 131I 90Y and actinides in targeted therapies discussing their mechanisms and applications. The article emphasizes personalized medicine combination therapies and emerging alpha-particle-based treatments. Challenges including radiation safety and side effects are also addressed. The review anticipates a promising future where radiogenic elements contribute to precise effective and patient-centered cancer care.
Mitigation of Radiation-induced Acute Hematopoietic System and Intestine Injury by Resveratrol-loaded Polymeric Nanoparticles after Whole Body Irradiation in Mice
Radiation-induced damage to the hematopoietic and gastrointestinal systems especially the intestine is a major concern for individuals exposed to whole-body radiation during an accident. Resveratrol has shown potential in mitigating radiation-induced toxicity but its efficacy may be limited by its low bioavailability. In this study we aimed to evaluate the effectiveness of resveratrol-loaded polymeric-based nanocapsules in mitigating radiation-induced injury in the hematopoietic system and intestine after whole-body exposure to radiation.
Sixty male mice were randomly divided into four groups: control radiation (single dose of 7.2 Gy of X-ray) only resveratrol-loaded polymeric-based nanocapsules (RES-ACN) only and radiation plus RES-ACN. Mice were exposed to a single dose of 7.2 Gy of X-ray radiation. RES-ACN was administered to the mice starting 24 h after irradiation up to day 7 post-irradiation. Then blood and tissue samples were collected for complete blood count and histopathological and biochemical evaluation. Survival analyses were also conducted.
The findings showed that RES-ACN significantly mitigated radiation-induced injury to the hematopoietic system and intestine. The histopathological evaluation showed the mitigation of villi shortening inflammation and mucous layer thickness following treatment with RES-ACN. Biochemical evaluation also demonstrated a significant increase in the activity of glutathione peroxidase and superoxide dismutase and a significant reduction in the concentrations of malondialdehyde and nitric oxide. Treatment with RES-ACN also showed a significant improvement in some of the blood parameters and increased survival compared to radiation only.
The findings suggest that resveratrol-loaded polymeric-based nanocapsules can be an effective approach to mitigate radiation-induced damage to the hematopoietic system and intestine after whole-body exposure to X-ray radiation in mice. Further research is needed to explore the optimal dose and timing of resveratrol administration and to investigate the potential for clinical translation of this approach.
Prediction of Recurrence using a Stacked Denoising Autoencoder and Multifaceted Feature Analysis of Pretreatment MRI in Patients with Nasopharyngeal Carcinoma
Nasopharyngeal Carcinoma (NPC) exhibits high incidence in southern China. Despite improved survival with intensity-modulated radiotherapy (IMRT) 10%-20% of patients experience local recurrence. Traditional TNM staging fails to reflect tumor heterogeneity necessitating robust recurrence prediction models. This study aimed to develop an MRI-based NPC recurrence prediction model by integrating radiomics deep learning and clinical features.
A total of 184 pathologically confirmed NPC patients receiving radical radiotherapy were included. After propensity score matching (1:1) 136 cases were analyzed. Stacked denoising autoencoder (SDAE) extracted deep features from contrast-enhanced T1-weighted MRI. Radiomic features (morphology texture first-order statistics) clinical parameters (gender age TNM stage) and SDAE features were combined to construct 12 models using SVM MLP logistic regression (LR) and random forest (RF). Performance was evaluated via AUC accuracy sensitivity and specificity with external validation (91 cases).
Model 1 (radiomics + SDAE + clinical features + SVM) achieved the highest AUC (0.89 95% CI: 0.84-0.93) accuracy (81.5%) sensitivity (67.3%) and specificity (97.9%). External validation showed AUC 0.83 sensitivity 88.9% and specificity 78%. The DeLong test confirmed no significant AUC difference between internal and external cohorts (P >0.05).
The fusion of SDAE-enhanced features outperformed traditional radiomics. SVM demonstrated optimal performance in small samples likely due to its high-dimensional feature handling and anti-overfitting capability. Limitations include single-center retrospective design and lack of functional imaging (DWI/PET) or molecular markers (EBV-DNA). Future multicenter prospective studies and multimodal data integration are warranted to enhance biological interpretability and clinical utility.
This model provides a tool for early recurrence risk stratification and personalized therapy optimization advancing precision medicine in NPC management.
An Analysis of the Radiosensitiser Applications in the Biomedical Field
Various types of radiosensitisers have been introduced from the past until the present day for applications in the biomedical field. However there is a lack of understanding and comparison between the various parameters introduced in addition to a lack of consensus among researchers on the optimal radiosensitiser for applications in the biomedical field.
This review aimed to investigate the usage of radiosensitisers in the biomedical field determine their important parameters and suggest radiosensitisers with potential among the analysed radiosensitisers.
This review has discussed several parameters for radiosensitisers including median lethal dose cell survival tumour size cell viability Dose Enhancement Factor (DEF) Reactive Oxygen Species (ROS) concentration radiosensitiser production complexity radiosensitiser administration technique and radiosensitiser toxicity. General trends regarding the development of radiosensitisers including the types effectiveness and their production complexity have also been discussed within this review article.
Enhancing Ketoprofen Solubility: A Strategic Approach Using Solid Dispersion and Response Surface Methodology
In the pharmaceutical sciences the solubility profile of therapeutic molecules is crucial for identifying and formulating drugs and evaluating their quality across the drug discovery pipeline based on factors like oral bioavailability metabolic transformation biodistribution kinetics and potential toxicological implications. The investigation aims to enhance the solubility parameters of ketoprofen (BCS-II class) which exhibits low solubility and high permeability.
In this method hydrotrope blends of aromatic sodium benzoate and electrolyte sodium acetate were employed to enhance the solubility parameter of ketoprofen. Several batches of solid dispersion of ketoprofen were made using a solvent evaporation method and the response surface method 32 factorial design was used to find the best one. The optimised formulation KSD9 underwent in-vitro drug dissolution DSC pXRD and SEM studies.
The optimized batch demonstrated substantial improvement in ketoprofen solubility attributed to mixed hydrotropy. The results indicated that both solubility and %CDR improved when hydrotropes were employed suggesting a direct proportionality between the rise in solubility and % CDR. Formulations KSD1-KSD9 exhibited solubility enhancements ranging from 2.23 to 5.77-fold along with an elevation in % CDR from 72.28% to 94.76%. This implies that the % CDR was modulated by the hydrotropes specifically influenced by the concentration levels of the independent variables. An increase in hydrotrope levels corresponded to an increase in % CDR. The positive coefficients in the quadratic equation for % CDR underscored the significant role of these independent variables in augmenting the in-vitro release of Ketoprofen. Similarly during a comparative dissolution investigation the optimized KSD9 formulation exhibited remarkable solubility and drug content compared to conventional Ketoprofen dispersible tablets.
The synergistic effect of combining two hydrotropic agents significantly increased the solubility of ketoprofen by up to 58 times. The results indicated that the independent variables exerted a positive influence on solubility and % CDR. Furthermore the responses were contingent on the specific hydrotropes selected which functioned as the independent variables. Analyzing the r2 and ANOVA results suggested that the dependent variables aligned well with the chosen model. Visual representations such as the 3D response surface plot and contour plot demonstrated the impact of each hydrotrope individually and when combined. Overall employing hydrotropes led to improved solubility and % CDR highlighting a direct proportionality between the rise in solubility and % CDR. Mixed hydrotropic lessens the toxicity associated with individual hydrotrope concentrations while also offering a sustainable and eco-friendly alternative. This study paves the way for future research aiming to improve the solubility of low- solubility drugs broadening their clinical applications.
Apigenin's Influence on Inflammatory and Epigenetic Responses in Rat Lungs After Radiotherapy
The lung is a moderately radio-sensitive organ. When cells are damaged due to accidental radiation exposure or treatment they release molecules that lead to the recruitment of immune cells accumulating inflammatory cytokines at the site of damage. Apigenin (Api) is a natural flavonoid known for its anti-inflammatory properties. In this study we investigated the radioprotective properties of Api in the lung.
Thirty-six Wistar rats were randomly assigned to nine groups: control radiation (Rad) CMC+Rad Api10+Rad and Api20+Rad. Api was administered with an intraperitoneal injection for 7 days after which the rats were irradiated with 6 Gy whole-body X-ray. At 6 and 72 hours post-irradiation the rats were euthanized and their lung tissue was extracted.
Radiation led to increased alveolar wall thickness and the infiltration of macrophages and lymphocytes. Furthermore the expression levels of inflammatory factors such as a nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-ĸB) Glycogen synthase kinase-3 beta (GSK-3β) transforming growth factor-beta1 (TGF-β1) and epigenetic factors including DNA methyltransferase 3a (DNMT3a) and Histone deacetylase 2 (HDAC2) were elevated in the lung tissue following radiation. Meanwhile the expression level of IκB-α decreased. However administration of Api (at both 10&20 mg/kg) reversed the adverse effects of radiation.
Api administration mitigated radiation-induced lung damage by reversing inflammatory and epigenetic changes.
Preclinical Aspects of [89Zr]Zr-DFO-Rituximab: A High Potential Agent for Immuno-PET Imaging
An early diagnosis of cancer can lead to choosing more effective treatment and increase the number of cancer survivors. In this study the preparation and preclinical aspects of [89Zr]Zr-DFO-Rituximab a high-potential agent for PET imaging of Non-Hodgkin Lymphoma (NHL) were evaluated.
DFO was conjugated to rituximab monoclonal antibody (mAb) and DFO-rituximab was successfully labeled with zirconium-89 (89Zr) at optimized conditions. The stability of the complex was assessed in human blood serum and PBS buffer. Radioimmunoreactivity (RIA) of the radioimmunoconjugate (RIC) was evaluated on CD20-overexpressing Raji cell line and CHO cells. The biodistribution of the radiolabeled mAb was studied in normal and tumor-bearing rodents. Finally the absorbed dose in human organs was estimated.
The radiolabeled compound was prepared with radiochemical purity (RCP) >99% (RTLC) and a specific activity of 180±1.8 GBq/g. The RCP of the final complex PBS buffer and human blood serum was higher than 95% even after 48 h post incubation. The RIA assay demonstrated that more than 63% of the radiolabeled compound (40 ng/ml 0.5 mL) was bound to 5×106 Raji cells. The biodistribution of the final product in tumor-bearing mice showed a high accumulation of the RIC in the tumor site in all intervals post-injection. Tumor/non-target ratios were increased over time and longer imaging time was suggested. The dosimetry data indicated that the liver received the most absorbed dose after the complex injection.
[89Zr]Zr-DFO-Rituximab represents a significant advancement in the field of oncological imaging and offers a robust platform for both diagnostic and therapeutic applications in the management of B-cell malignancies.
Left Ventricular Wall Motion as an Additional Valuable Parameter in Diabetic Patients with Normal Myocardial Perfusion Imaging
Gated SPECT is an established technique for assessment of left ventricular function in cardiovascular disease patients. However there is little information about the influence of diabetes mellitus on gated SPECT parameters. This study was established to assess gated SPECT parameters in Diabetes Mellitus (DM) and non-diabetes mellitus (non-DM) patients with normal Myocardial Perfusion Imaging (MPI).
In this analytical cross-sectional study 314 patients (157 DM 157 non-DM) with normal MPI were enrolled. Prevalence of risk factors for CAD like hypertension (HTN) and dyslipidemia were found to be significantly higher (p <0.01) in DM patients compared to non-DM.
No statistically significant difference was observed among the TID ESV EDV PFR TTPF and Wall Thickness (WT) parameters between DM and non-DM patients. Wall motion (Wm) in DM patients was significantly higher compared to non-DM patients. (3.9 ± 0.51 vs. 2.69 ± 0.48 for DM and non-DM patients respectively p-value:0.01). Also there was no significant difference in Wm in the two groups with and without HTN. This shows the independent effect of DM on the Wm.
This study believes that the Wm parameter should be noted for the early diagnosis or prevention of heart disease in DM patients. These findings can indicate the gradual changes in the movements of the left ventricle and the beginning of the progression of diabetic cardiomyopathy.