A novel 99m Tc-diester complex as tumor targeting agent: Synthesis, radiolabeling, and biological distribution study.

The target of this study is the synthesis of a new diester derivative and radiolabeling with one of the most effective diagnostic radioisotopes to be investigated as a novel targeting radiotracer for tumor imaging. 10-[2-(9-Carboxynonanoyloxy)propoxy]-10-oxodecanoic acid was synthesized in excellent yield and characterized by Fourier-transform infrared spectroscopy, mass, 1 H-NMR, and 13 C-NMR spectra. The diester was technetium-99m (99m Tc) radiolabeled by direct technique using sodium dithionite as a reducing agent. The labeling parameters such as diester amount, reducing agent amount, pH of the medium, and reaction time were optimized. High radiochemical yield of 95.10 ± 0.41% and in vitro stability in serum up to 12 h have been obtained on complexation of the synthesized diester with Tc-99m. Evaluation of the diester anticancer activity against breast cancer cell line (MCF-7) showed high percent of inhibition about 61.5% at 100 µg/ml. The rhenium complex of the diester was synthesized and characterized by liquid chromatography-mass spectrometry (ESI) and elemental analysis depending on the strong chemical resemblance between Tc and Re. Biodistribution studies of 99m Tc-diester complex showed high target to nontarget ratio (T/NT) equals 6.24 ± 0.09 in tumor-bearing mice at 30-min postinjection, suggesting this complex could be used as hopeful solid tumor-imaging agent.

"Tau Protein Targeting Via Radioiodinated Azure A For Brain Theranostics: Radiolabeling, Molecular Docking, in vitro And in vivo Biological Evaluation".

Azure-A is one of the phenothiazines (PTZs) derivatives which for decades have been used as antipsychotic drugs due to good lipophilic characteristics which enable them to pass through the blood brain barrier (BBB), besides the important property of enabeling investigation of the pathological forms of aggregated tau protein found in the neurons of the central nervous system. Radioiodination of Azure-A was carried out via an electrophilic substitution reaction using chloramine-T as oxidizing agent. The influence of various reaction parameters and conditions on radioiodination efficiency was investigated, and a high radiochemical yield of 92.07 ± 0.9 % was obtained. An in vitro cytotoxicity study of iodinated Azure-A on three cell lines (HCT-116, human colon carcinoma cell line; Hep-G2, liver carcinoma cell line and HFB-4, normal human melanocytes) was carried out, and the data revealed that ioiodinated Azure A has no to very low toxic effect. The in vivo biodistribution study of 131 I-Azure A showed a high brain uptake of 6.15 ± 0.09 % injected dose/g tissue organ at 30 minutes post-injection, and its retention in brain remained high up to 2 hours, whereas the clearance from the body appeared to proceed via the renal system. The experimental data were confirmed by the molecular docking studies to predict the effect of radioiodination on the binding affinity of the parent molecule (Azure A) to tau paired helical filaments (PHFs). Both ligands showed better binding to S2 and S3 pockets of (PHFs). Consequently, radioiodinated Azure A seems to be a good candidate as an imaging agent for taupathies such as Alzheimer's disease, chronic traumatic encephalopathy, and corticobasal degeneration. Furthermore, it could be a very potent theranostics agent for brain tumors.

Potential production of Ac-225 at Egyptian second research reactor (ETRR-2) through neutron induced transmutation of Ra-226.

A considerable focus has been paid to the production of 225Ac due to its effective therapeutic action in alpha-targeted radiotherapy. Considering the future global clinical demand, it is necessary to increase the production capacity of 225Ac. A feasibility study was conducted to investigate the production of 225Ac through neutron induced transmutation of 226Ra at the Egyptian Second Research Reactor (ETRR-2) using the MCNPX code. The calculations were carried out for 1 g of 226Ra target exposed to the highest neutron flux in the irradiation grid surrounding the reactor core. The 227Ra, 225Ra, 227Ac, and 225Ac generated activities as a function of irradiation and decay times were estimated. Our study revealed that in this non-linear production process, 39.22 MBq of pure 225Ac could be obtained after three days of irradiation, while 148.74 MBq could be obtained after fifteen days of continuous irradiation.

Adsorption of 60Co(II) and 152+154Eu(III) radionuclides by a sustainable nanobentonite@sodium alginate@oleylamine nanocomposite.

A sustainable and efficient nanobentonite@sodium alginate@oleylamine (Nbent@Alg@OA) nanocomposite has been successfully synthesized via coating reaction of nanobentonite (Nbent) with alginate (Alg) and oleylamine (OA). The nanocomposite has been characterized and examined for the adsorption of 60Co(II) and 152+154Eu(III) radionuclides from simulated radioactive waste solution. FT-IR, XRD, SEM, and HR-TEM techniques have been applied to confirm the structural and morphological characteristics of the Nbent@Alg@OA nanocomposite. The effects of various parameters, such as pH of the medium, initial concentration of the radionuclides, contact time, and temperature on the adsorption of 60Co(II) and 152+154Eu(III) radionuclides were investigated by the batch adsorption technique. The results revealed that the optimum pH values for the adsorption of 152+154Eu (III) and 60Co (II) radionuclides were 4 and 5, respectively. The adsorption capacity of 152+154Eu(III) (65.6219 mg/g) was found greater than that of 60Co(II) (47.3469 mg/g). The adsorption process was found to be well described by the pseudo-second-order kinetic model. Furthermore, the equilibrium isotherm evaluation revealed that the Langmuir model was adequately matched with the adsorption data. According to the thermodynamic characteristics, the adsorption process was endothermic and spontaneous. Regeneration and reuse of Nbent@Alg@OA nanocomposite confirmed that the recycled nanocomposite was sufficiently efficient in several successive practical applications.

Marshalling the Potential of Auger Electron Radiopharmaceutical Therapy.

Auger electron (AE) radiopharmaceutical therapy (RPT) may have the same therapeutic efficacy as α-particles for oncologic small disease, with lower risks of normal-tissue toxicity. The seeds of using AE emitters for RPT were planted several decades ago. Much knowledge has been gathered about the potency of the biologic effects caused by the intense shower of these low-energy AEs. Given their short range, AEs deposit much of their energy in the immediate vicinity of their site of decay. However, the promise of AE RPT has not yet been realized, with few agents evaluated in clinical trials and none becoming part of routine treatment so far. Instigated by the 2022 "Technical Meeting on Auger Electron Emitters for Radiopharmaceutical Developments" at the International Atomic Energy Agency, this review presents the current status of AE RPT based on the discussions by experts in the field. A scoring system was applied to illustrate hurdles in the development of AE RPT, and we present a selected list of well-studied and emerging AE-emitting radionuclides. Based on the number of AEs and other emissions, physical half-life, radionuclide production, radiochemical approaches, dosimetry, and vector availability, recommendations are put forward to enhance and impact future efforts in AE RPT research.

A novel dipeptide coupled with pyrazine-oxadiazole derivative as a potential antitubercular agent: Synthesis, radioiodination and bioevaluation.

Tuberculosis (TB) is a disease caused by Mycobacterium and usually attack the lung. Synthesis of new dipeptide derivatives attached to antitubercular active heterocyclic rings like pyrazine and 1,3,4-oxadiazole called ethyl 2-(2-(5-((pyrazin-2-ylamino) methyl)-1,3,4-oxadiazol-2-ylthio) acetamido) acetamido)-3-(4-hydroxyphenyl) propanoate (EPOGTP) and iodinated EPOGTP are reported. The compounds have been characterized by mass, FT-IR and 1H NMR spectroscopy. Their in vitro investigation against Mycobacterium tuberculosis cell line indicated good IC50value of 210 µg/ml for EPOGTP and 86 µg/ml for iodo-EPOGTP. For study the biodisriution, the direct radioiodination of EPOGTP with iodine-131 using mild oxidizing agent, N-Bromosuccinimide (NBS), was performed and optimized for obtaining the maximum radiochemical purity (97.3 ± 0.47%). Then, the in vivo biodistribution in healthy mice showed good accumulation of radioiodinated EPOGTP in lung of about 41.83 ± 0.23% (the percentage of injected dose per gram of organ) at 15 min post-injection. As a conclusion, the synthetized dipeptide and its iodinated derivative could be further evaluated as a potential antitubercular agents.

IAEA Activities on 67Cu, 186Re, 47Sc Theranostic Radionuclides and Radiopharmaceuticals.

Despite interesting properties, the use of 67Cu, 186Re and 47Sc theranostic radionuclides in preclinical studies and clinical trials is curtailed by their limited availability due to a lack of widely established production methods. An IAEA Coordinated Research Project (CRP) was initiated to identify important technical issues related to the production and quality control of these emerging radionuclides and related radiopharmaceuticals, based on the request from IAEA Member States. The international team worked on targetry, separation, quality control and radiopharmaceutical aspects of the radionuclides obtained from research reactors and cyclotrons leading to preparation of a standard recommendations for all Member States. The CRP was initiated in 2016 with fourteen participants from thirteen Member States from four continents. Extraordinary results on the production, quality control and preclinical evaluation of selected radionuclides were reported in this project that was finalized in 2020. The outcomes, outputs and results of this project achieved by participating Member States are described in this minireview.

Synthesis of chitosan-acrylic acid/multiwalled carbon nanotubes composite for theranostic 47Sc separation from neutron irradiated titanium target.

A simple and efficient separation method of carrier-free 47Sc from neutron irradiated titanium target using a novel chitosan-acrylic acid/multiwalled carbon nanotubes (CS-AA/MWCNTs) composite was established. The synthesis of the CS-AA/MWCNTs composite was achieved using gamma radiation-induced template polymerization. The grafting efficiency (GE%) of AA on CS onto the surface of f-MWCNTs reached a maximum of~84% under the optimized conditions (30 wt% CS, 1.0 wt% AA, 0.15 wt% f-MWCNTs, >0.2 wt% N,N'-Methylenebisacrylamide (NMBA), and irradiation dose ~25 kGy). Different analyses (FT-IR, SEM, TGA and DTA) were examined for confirming the structural morphology and mechanical properties of the new synthesized composite. Interestingly, the CS-AA/MWCNTs composite depicted a selective adsorption of Sc(III) rather than Ti(IV) ions at pH 5 with adsorption efficiency of ~93.93%. The ionic exchange separation of no-carrier-added (NCA)47Sc(III) from irradiated TiO2 target on CS-AA/MWCNTs composite packed column efficiently eluted 47Sc(III) by 91 ± 0.8% using 1 M HCl solution. The quality control tests (radionuclidic, radiochemical, and chemical purities) for the eluted 47Sc(III) clarified its high purity and validity for cancer theranostics.

Biosynthetic new composite material containing CuO nanoparticles produced by Aspergillus terreus for 47Sc separation of cancer theranostics application from irradiated Ca target.

Copper oxide nanoparticles (CuO NPs) are needed in various fields, especially in the biomedical field. CuO NPs was obtained from Aspergillus terreus filtrate. CuO NPs structure was confirmed by UV-Vis spectrophotometry, as well as Fourier transform infrared (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). XRD offers the nanoparticles purity of CuO biosynthesis. CuO NPs are spherical when examined with TEM. The average size of CuO NPs from TEM was 15.75 ± 3.95 nm. New composite of P (AA-AN)-NPs CuO was synthesized by biotechnology and the induced γ-radiation. The distribution coefficient value (Kd) of 47Sc(III) as well as 47Ca(II) ions for the synthetic new composite was determined by batch technique. Radiochemical separation of 47Sc(III) from irradiated calcium target was studied using chromatographic column packed with the new composite material. The recovery yield of 78 ± 1.2% for 47Sc(III) was obtained using 1 M HCl. The quality control tests (chemical, radionuclide and radiochemical purities) of the eluted 47Sc confirmed that it's adequate for nuclear medicine applications.