Preparation and evaluation of radiolabeled acetaminosalol microspheres: A new potential selective radiotracer for ulcerative colitis early diagnosis.

Acetaminosalol labeling reaction with technetium-99m was optimized, and the radiocomplex was obtained in a high radiochemical yield of 98.9 ± 0.6% and high stability (>30 h). The tracer was characterized, and its binding to the PPARγ receptor was assessed in silico. To reduce radiation exposure to non-target organs and increase accumulation in the colon, the tracer was formulated as pH-sensitive microspheres with a mean particle size of 201 ± 2.1 µm, a polydispersity index of 0.18, a 25.3 ± 3.6 zeta potential, and 98.6 ± 0.33% entrapment efficiency. The system suitability was assessed in vivo in normal and ulcerative rats, and the biodistribution profile in the colon showed 56.5 ± 1.4% localization within 4 h. Blocking study suggested the selectivity of the tracer to the target receptor. Overall, the reported data encouraged the potential use of the labeled microspheres to target ulcerative colitis.

99mTc-linezolid as a radiotracer for brain abscess: Labeling, in silico docking, and biodistribution studies.

Brain abscess is a life-threatening condition that requires a timely and accurate diagnosis. In this study, linezolid, an oxazolidinone antibiotic, was labeled with technetium-99m according to the stannous chloride method. The labeling reaction factors were studied and optimized to achieve a high yield (97.4 ± 2.3%). The 99mTc-linezolid was radio- and physico-chemically characterized to assess its suitability as a radiopharmaceutical for the brain. In-silico docking to target peptidyltransferase showed an optimal binding fit (energy = -66.6 Kcal/mol). The complex was biologically evaluated in-vitro using binding assays in alive and heat-killed bacteria and in-vivo in an MRSA brain infection model. All results suggested that the labeled complex could potentially be a new nuclear imaging agent to diagnose and localize brain abscesses specifically.

Cyanopyridinone- and Cyanopyridine-Based Cancer Cell Pim-1 Inhibitors: Design, Synthesis, Radiolabeling, Biodistribution, and Molecular Modeling Simulation.

In this study, two new series of 3-cyanopyridinones (3a-e) and 3-cyanopyridines (4a-e) were synthesized and evaluated for their cytotoxicity and Pim-1 kinase inhibitory activity adopting 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and in vitro Pim-1 kinase inhibition assay, respectively. Most of the tested compounds revealed promising cytotoxicity against HepG-2, HCT-116, MCF-7, and PC-3 cell lines. Among them, compounds 4c and 4d showed more potent cytotoxicity against the HePG2 cell line with IC50 = 8.02 ± 0.38 and 6.95 ± 0.34 µM, respectively, than that of the reference 5-FU (IC50 = 9.42 ± 0.46 µM). Moreover, compound 4c was more potent against HCT-116 (IC50 = 7.15 ± 0.35 µM) than 5-FU (IC50 = 8.01 ± 0.39 µM), while compound 4d with IC50 = 8.35 ± 0.42 µM displayed comparable activity to that of the reference drug. Furthermore, high cytotoxic activity was manifested by compounds 4c and 4d against MCF-7 and PC3 cell lines. Our results have also indicated that compounds 4b, 4c, and 4d elicited remarkable inhibition of Pim-1 kinase; 4b and 4c showed equipotent inhibitory activity to that of the reference quercetagetin. Meanwhile, 4d displayed IC50 = 0.46 ± 0.02 µM, showed the best inhibitory activity among the tested compounds, and was more potent than quercetagetin (IC50 = 0.56 ± 0.03 µM). For optimization of the results, docking study of the most potent compounds 4c and 4d in the Pim-1 kinase active site was carried out and compared with both quercetagetin and the reported Pim-1 inhibitor A (VRV), and the results were consistent with those of the biological study. Consequently, compounds 4c and 4d are worthy of further investigations toward the discovery of Pim-1 kinase inhibitors as drug candidates for cancer therapy. Compound 4b was successfully radiolabeled with radioiodine-131, and its biodistribution in Ehrlich ascites carcinoma (EAC)-bearing mice showed more observable uptake in tumor sites, and hence, it can be introduced as a new radiolabeled agent for tumor imaging and therapy.

Preparation and evaluation of radiolabeled gliclazide parenteral nanoemulsion as a new tracer for pancreatic ß-cells mass.

PURPOSE: The present investigation aims to develop and evaluate a radiopharmaceutical for targeting and assessing ß-cells mass based on gliclazide, an antidiabetic drug that specifically binds the sulfonylurea receptor unique to the ß-cells of the pancreas. METHODS: Conditions were optimized to radiolabel gliclazide with radioiodine via electrophilic substitution reaction. Then, it was formulated as a nanoemulsion system using olive oil and egg lecithin by hot homogenization followed by ultrasonication. The system was assessed for its suitability for parenteral administration and drug release. Then, the tracer was evaluated in silico and in vivo in normal and diabetic rats. RESULTS AND CONCLUSIONS: The labeled compound was obtained with a high radiochemical yield (99.3 ± 1.1%) and good stability (>48 h). The radiolabeled nanoemulsion showed an average droplet size of 24.7 nm, a polydispersity index of 0.21, a zeta potential of -45.3 mV, pH 7.4, an osmolality of 285.3 mOsm/kg, and viscosity of 1.24 mPa.s, indicating suitability for parenteral administration. In silico assessment suggested that the labeling did not affect the biological activity of gliclazide. The suggestion was further supported by the in vivo blocking study. Following intravenous administration of nanoemulsion, the pancreas uptake was highest in normal rats (19.57 ± 1.16 and 12 ± 0.13% ID) compared to diabetic rats (8.51 ± 0.16 and 5 ± 0.13% ID) at 1 and 4 h post-injection, respectively. All results supported the feasibility of radioiodinated gliclazide nanoemulsion as a tracer for pancreatic ß-cells.

Radioiodination, nasal nanoformulation and preliminary evaluation of isovanillin: A new potential brain cancer-targeting agent.

Brain cancer is a challenging disease to treat using conventional approaches. The present investigation aimed to develop a radiopharmaceutical targeting brain cancer based on natural isovanillin. Different parameters were optimized, resulting in high radiolabeling efficiency (97.3 ± 1.2%) and good stability (<48 h). The tracer was formulated for intranasal delivery in a chitosan nanoparticles system with a mean particle size of 141 ± 2 nm, a polydispersity index of 0.23 ± 0.02, and a zeta potential of -17.4 ± 0.3 mV to enhance nasal uptake and surmount the blood-brain barrier. The system was characterized and assessed in-vitro for suitability and specificity and evaluated in-vivo in normal and tumorized mice. The biodistribution profile in brain tumor showed 20.5 ± 0.4 %ID/g localization and cancer cell targeting within 60 min. Improvement in brain tumor uptake resulted from both the nanoformulation and nasal administration of iodoisovanillin. Overall, the reported results encourage the potential use of the nanoformulated labeled compound as an anticancer agent.

Preparation and evaluation of radioiodinated avanafil: A novel potential radiopharmaceutical for the diagnostic evaluation of erectile dysfunction.

Avanafil, a selective second-generation phosphodiesterase-5 inhibitor, was successfully labeled with iodine-125 via electrophilic and different factors affecting the labeling efficiency were studied. The labeled compound exhibited in-vitro stability of more than 24 h with a maximum labeling yield of up to 98.4 ± 1.9 %. Molecular modeling and in-vitro assessment of tracer inhibitory activity were performed to ensure that radiolabeling did not affect its binding ability to the target. Biodistribution studies were performed in normal rats and models of erectile dysfunction. The tracer specifically accumulated in the penis, and the clearance appeared to take place via the hepatobiliary route. Results suggested the usefulness of radiolabeled avanafil as a promising tracer for erectile dysfunction.

Preparation and preliminary evaluation study of [131I]iodocolchicine-gallic-AuNPs: a potential scintigraphic agent for inflammation detection.

BACKGROUND: Nanomedicine offers great potential for scintigraphic diagnostic imaging with lower risk and higher quality compared to other traditional techniques. OBJECTIVES: This work aimed to develop and evaluate gold nanoparticles combined with gallic acid (gallic-AuNPs) and [131I]iodocolchicine as a scintigraphic probe for inflammation. METHODS: [131I]iodocolchicine-gallic-AuNPs were synthesized via chemical reduction method where gallic acid was used as reducing agent and [131I]iodocolchicine was used as stabilizing agent. Then a characteristic profile for the synthesized nano-platform was performed including size analysis, zeta potential, radiochemical yield and in-vivo biodistribution in inflammation bearing mice. RESULTS AND CONCLUSION: This platform was successfully synthesized with good stability, appropriate particle size (10 nm diameter for AuNPs), and high radiochemical purity for [131I]iodocolchicine (96.79%). The in-vivo study indicated that [131I]iodocolchicine-gallic-AuNPs accumulated with a high target to non-target ratio in intravenous injection and high retention value in intra-inflammation injection in inflammation model. The obtained data supported the usefulness of the new platform ([131I]iodocolchicine-gallic-AuNPs) as a tracer for the detection and localization of inflammation.

Preparation, characterization and evaluation of [125I]-pirarubicin: A new therapeutic agent for urinary bladder cancer with potential for use as theranostic agent.

Improving urinary bladder cancer diagnosis, follow-up, and therapy tools to overcome existing limitations and increase survival rates is a highly desirable goal. In the current investigation, pirarubicin, a new generation antineoplastic anthracycline, was labeled with [125I] via an electrophilic substitution reaction. The reaction parameters were studied to optimize the iodination process. The labeled compound showed high radiochemical yield (98.5 ± 2.1%) and consistently remained above 90% for more than 20 h at room temperature and in the presence of serum at 37 °C. The binding of [125I]-pirarubicin to its target DNA-human topoisomerase II complex was assessed in-silico. The in-vitro tracer uptake by cancer cells was high and reached saturation (88.4 ± 2.3%) after 3 h with nuclei to cells ratio of 40 ± 1.2%. The labeled compound antiproliferative effect was much stronger than the unlabelled pirarubicin, as cleared by the growth inhibition test. Radiotoxicity improved cancer cells drug cytotoxicity. The in-vivo evaluation results showed that the [125I]-pirarubicin tends to preferentially accumulate in urinary bladder cancerous tissues.

Radiolabeling, characterization, and preclinical evaluation of plazomicin: A potential tracer for bacterial infection.

In this study, 99m Tc-plazomicin, a new radio-antibiotic complex, was prepared specifically for bacterial infection localization and monitoring. Factors affecting the labeling reaction were studied and optimized to obtain a high yield (98.8 ± 0.2%). In silico, radiochemical and physicochemical characterization and biodistribution were performed to assess the complex aptness as a radiopharmaceutical. The complex was biologically evaluated in vitro using bacteria and in vivo using different inflammation models (sterile, bacterial, and fungal). Uptake in the bacterial model was highest (7.8 ± 0.3%). Results indicated that the technetium label did not alter the antibiotic biological behavior and backed the usefulness of 99m Tc-plazomicin as a potential tracer.

Labelling, molecular modelling and biological evaluation of vardenafil: a potential agent for diagnostic evaluation of erectile dysfunction.

99mTc-tricarbonyl-vardenafil was specifically radiosynthesized for diagnostic evaluation of erectile dysfunction with a radiochemical yield ~97.2%. It was stable in saline up to 15h and in serum for more than 6h. The radiocomplex was lipophilic with a partition coefficient ~1.32 and plasma protein binding 72-76%. Its structure was determined using molecular mechanics and confirmed by NMR. In-silico docking to its target PDE5 enzyme was performed. The radiocomplex inhibitory activity was assessed and its IC50 was 0.7nM. Biodistribution in normal rats and biological evaluation in rat models of erectile dysfunction were performed. The results strongly suggested that 99mTc-tricarbonyl-vardenafil is a good candidate to image erectile dysfunction in humans.

Preparation, characterization and evaluation of (186) Re-idarubicin: a novel agent for diagnosis and treatment of hepatocellular carcinoma.

Hepatocellular carcinoma is a widely prevalent cancer, and hence, the development of radiopharmaceuticals for its management is an important issue. In the current investigation, the complexation of idarubicin with (186) Re was studied. Optimum labelling conditions were found to be 4 mg idarubicin, 1.5 mg stannous chloride dihydrate and ~70 MBq Re-186 at pH 7. The complex showed ~97.6% RCY value at 20 min and remained stable up to 24 h in the presence of 2.5 mg ascorbic acid. Molecular docking was performed to evaluate the complex binding to its target DNA-human topoisomerase II complex. Result of the in vivo evaluation showed that the complex tends to preferentially localize in cancerous tissues. The in vitro cell growth inhibition assay showed that the effect of the (186) Re-idarubicin was stronger than the effect of cold idarubicin, which strongly suggested that its cytotoxicity was mainly because of radiotoxicity rather than chemotherapeutic activity.

Technetium-99 m labeling and evaluation of olsalazine: a novel agent for ulcerative colitis imaging.

Ulcerative colitis is a chronic disease having a regressive nature. Commonly used diagnostic methods have the disadvantage to be invasive, time-consuming, and expensive. Therefore, a new sensitive method for the detection and monitoring of disease activity is urgently needed in clinical practice. In the current investigation, radio complexation of olsalazine with technetium-99m, its characterization, and optimization of the labeling conditions were explored. Optimum radiochemical yield of (99m) Tc-olsalazine (97.6% ± 1.8%) was obtained via direct complexation with technetium-99m (~200 MBq) in the presence of stannous chloride dihydrate (100 µg) as reducing agent at pH 6. It was observed that the complex showed significant in vitro stability in serum at 37°C for more than 11 h. The computer-generated optimized geometries of the (99m) Tc-olsalazine were reported, and biodistribution studies were carried out using chemically and microbiologically mice-induced ulcerative colitis models. The tracer showed a good localization in both models and was excreted mainly via liver and to some extent via kidney. Imaging can be performed at 1-2 h post-injection; at that time, the background activity has cleared, and the activity is concentrated in the target site. All the gathered biological data supported the usefulness of (99m) Tc-olsalazine as a potential imaging agent for ulcerative colitis.