Current Radiopharmaceuticals - Volume 18, Issue 2, 2025

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.

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.

Zirconium-89 (⁸⁹Zr, t1/2=3.27d) is an important β⁺ emitting radionuclide used in Positron Emission Tomography (PET) immuno studies due to its unique characteristics and increased demand due to simple and cost-effective production capacity. Production of ⁸⁹Zr is achieved primarily through solid natural yttrium targets via different target preparation methodologies, such as electrodeposition, pressed foils, and spark plasma sintering. In this study, we have investigated the pressed solid target methodology.

The Yttrium Oxide (Y2O3) powder was pressed to pellet form and stacked over a different back support plate, such as platinum (Pt), niobium (Nb), and tantalum (Ta). The target was irradiated with approximately 12 MeV proton beam for 10-60 minutes at 20µA current. The irradiated target was purified through a solid phase extraction method via hydroxamate-based resin by manual or automatic approach. The purified ⁸⁹Zr was analyzed using gamma scintigraphy, and specific activity was calculated through Deferoxamine (DFO) chelation.

⁸⁹Zr radionuclide via pressed target was effectively produced with a production yield of 20-30 MBq/µA.h, and the purification was achieved in 35 minutes with (87.46)% average recovery and >98% purity while using automated purification, but manual purification took 2 hours with (91 ± 2)% recovery and >98% purity. The production yield was comparable to the reported pressed target approach. Deferoxamine chelation with ⁸⁹Zr-oxalate was performed with purity >98% and specific activity of 25-30 µCi/μmol.

In this study, we explored the production of ⁸⁹Zr by pressed targets and purification via manual or automated methods with good radionuclide purity. The chelation with DFO or its analog was performed with good labeling efficiency and stability.

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.

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.

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.