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.

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.

Synthesis and biological evaluation of [131I]iodocarvedilol as a potential radiopharmaceutical for heart imaging.

The optimization of the radiolabeling yield of carvedilol with iodine-131 was described. Dependence of the labeling yield of [131I]iodocarvedilol on the concentration of carvedilol, chloramine-T content, pH of the reaction mixture and reaction time was studied in details. Carvedilol was labeled with iodine-131 at pH 6 with a labeling yield of 92.6 ± 2.77% by using 100 µg carvedilol, 200 µg chloramin-T (CAT) and 30 min reaction time. The formed [131I]iodocarvedilol was nearly stable for a time up to one day. Biodistribution of [131I]iodocarvedilol was investigated in experimental animals. [131/123I]iodocarvedilol was located in the heart with a concentration of 19.6 ± 0.41% of the injected dose at 60 min post injection. It has a high heart uptake and heart to liver ratio, both of which are beneficial for high-quality SPECT (single-photon emission computerized tomography) myocardial imaging. [131/123I]iodocarvedilol solve most the drawbacks of the FDA (Food and Drug Administration) approved 99mTc-sestamibi.

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.

Miniaturized chromatographic systems for radiochemical purity evaluation of 131I-Ferulic acid as a new candidate in nuclear medicine applications.

Recently, the anticancer activity of ferulic acid (FA) which is a caffeic acid derivative has been reported. Therefore, in this study FA was radiocaped with 131I- to explore its potential as a tumor targeting agent. The radiolabeling process was carried out via electrophilic substitution reaction. The factors affecting labeling yield were optimized and the radiochemical purity (RCP) was assessed by various analytical techniques including paper chromatography (PC), thin layer chromatography (TLC), instant thin layer chromatography (ITLC), paper electrophoresis (PE) and high-performance liquid chromatography (HPLC). The RCP assay was extended to the utilization of miniaturized techniques including miniaturized PC (mini-PC), mini-TLC and mini-column chromatography (silica, sephadex-G25). Validation of mini-TLC, as one of 131I-FA RCP assay methods, was done according to ICH guidelines. Biodistribution studies of 131I-FA were performed on Ehrlich solid tumor bearing mice at various time points (5, 30, 60, 120 and 240 min), post injection. The radiolabeling yield of 131I-FA was 96.23 ± 0.45% and the miniaturized chromatographic systems showed high efficacy in RCP evaluation comparable to the conventional ones. Mini-TLC was proved to be specific, accurate, precise and linear. The tumor uptake of 131I-FA in solid tumor bearing mice was 4.35 ± 0.41 ID/g at 60 min with 2.79 as a tumor/muscle ratio. Consequently, 131I-FA could be used as a tumor targeting agent for nuclear medicine applications and the fast reaction monitoring could be achieved using miniaturized chromatographic techniques.

Radioiodination and in vivo assessment of the potential of newly synthesized pyrrolizine-5-carboxamides derivative in tumor model.

Recently, pyrrolizine derivatives have been reported to possess numerous anticancer activities. In a previous study, (EZ)-6-((4-chlorobenzylidene)-amino)-7-cyano-N-(p-tolyl)-2,3-dihydro-1H-pyrrolizine carboxamide (EZPCA) compound was synthesized and the cytotoxic activity of EZPCA toward COX-2 enzyme (overexpressed in cancer cells) was reported. In order to assess the suitability of this compound as a promising pilot structure for in vivo applications, EZPCA was radiolabeled with radioiodine-131 (131I) and various factors affecting radiolabeling process were studied. Quality control studies of [131I]iodo-EZPCA were performed using paper chromatography and HPLC was used as a co-chromatographic technique for confirming the radiochemical yield. Biodistribution studies of [131I]iodo-EZPCA were undertaken in normal and tumor bearing mice. The radiochemical yield percentage of [131I]iodo-EZPCA was 94.20 ± 0.12%. The biodistribution results showed evident tumor uptake of [131I]iodo-EZPCA with promising target/non-target (T/NT) ratios. As a conclusion, these data suggest that [131I]iodo-EZPCA had high binding efficiency, high tumor uptake and sufficient stability to be used be used in diagnostic studies.

131I-trazodone: preparation, quality control and in vivo biodistribution study by intranasal and intravenous routes as a hopeful brain imaging radiopharmaceutical.

OBJECTIVES: The preparation of 131I-trazodone hydrochloride and its biological evaluation as a promising brain imaging radiopharmaceutical using two routes of administration. MATERIAL AND METHODS: Trazodone (TZ) was radiolabelled with 131I using direct electrophilic substitution, and different factors affecting labelling yield were studied. Quality control of 131I-TZ was carried out using ascending paper chromatography, paper electrophoresis, and high pressure liquid chromatography (HPLC). In vivo biodistribution of 131I-TZ was evaluated in Swiss albino mice using 3 methods: intravenous 131I-TZ solution (IVS), intranasal 131I-TZ solution (INS), and intranasal 131I-TZ microemulsion (INME). RESULTS: Optimum labelling yield of 91.23±2.12% was obtained with in vitro stability of 131I-TZ up to 6h at room temperature. The biodistribution results showed a notably higher and sustained brain uptake for INME compared to IVS and INS at all time intervals. In addition, heart and blood uptake levels for INME were lower than those for IV solution which, in turn, could decrease the systemic side effects of trazodone. Also, the 131I-trazodone INME brain uptake of 6.7±0.5%ID/g was higher than that of 99mTc-ECD and 99mTc-HMPAO (radiopharmaceuticals currently used for brain imaging). CONCLUSION: 131/123I-trazodone formulated as INME could be used as a promising radiopharmaceutical for brain imaging.

(125)I labeling of clomiphene and biodistribution studies for possible use as a model in breast cancer imaging.

Clomiphene has growth-inhibitory effects of breast cancer cells, clomiphene was successfully labeled with (125)I via direct electrophilic substitution reaction with labeling yield 97%. It was obtained at optimum substrate amount of 0.5mg, Chloramine-T was used as an oxidizing agent at optimum amount of 25µg. Labeling reactions was done at pH 5 at ambient temperature. This study showed good in vitro and in vivo stability of the (125)I-clomiphene. The radiolabeled compound showed high ascetic fluid uptake of 18.12±0.27% at 30min post-injection. Solid tumor uptake of (125)I-clomiphene was 12.48±0.32% at 30min post-injection. This data revealed the localization of tracer in tumor tissue with high percent sufficient to use (125)I-clomiphene as a promising tool for the diagnosis of breast cancer.

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.

Radioiodination of 2,3-dimethyl-4H-furo[3,2-c]coumarin and biological evaluation in solid tumor bearing mice.

Compound 2,3-dimethyl-4H-furo[3,2-c]coumarin is a coumarin derivative that could be labeled with 125I. The process of labeling was started using 1mg of the compound, 50µg CAT oxidizing agent, 30min as reaction time at pH with a yield about 95%. The 125I-coumarin derivative was stable for about 48h. Radiochemical purity of the labeled compound was performed by electrophoresis and HPLC. The labeled compound was separated with purity about 95%. Tumor transplantation to produce a solid tumor in the right leg of albino mice was made by intramuscular injection of 2×106 EAC (Ehrlish acittes carcinoma cells). Biodistribution study of 125I-coumarin derivative revealed that the uptake in tumor bearing leg was over 5% at 1h and 4h post-injection. This uptake encourages the use of 123I-coumarin derivative in imaging of tumor sites.

Labeling of tannic Acid with technetium-99m for diagnosis of stomach ulcer.

Tannic acid is a polyphenolic compound that could be labeled with technetium-99m. To produce about 90% yield of (99m)Tc-tannic acid in acidic media (pH), the conditions required were 150 µg tin chloride, 30 min reaction time, and 200 µg of the substrate. (99m)Tc-tannic was stable for 6 h. Oral biodistribution of (99m)Tc-tannic showed that it concentrated in the stomach ulcer to reach about 50% of the total injected dose at 1 h after orall administration. This concentration of (99m)Tc-tannic in stomach ulcer may be sufficient to radio-image the presence of ulcer in the stomach.