Facile One-Pot Strategy for Radiosynthesis of 99mTc-Doxycycline to Diagnose Staphylococcus aureus in Infectious Animal Models.

The accurate and early diagnosis of infection is an important feature in the biomedical sciences for better treatment and to decrease the rate of morbidity associated with diseases. Doxycycline (DC) is a semisynthetic antibiotic that belongs to tetracycline family and usually prescribed to treat a variety of infections. The objective of the present research work was to develop a new radiopharmaceutical 99mTc-Doxycycline (99mTc-DC), by using SnCl2·2H2O as a reducing agent for diagnostic applications. It was confirmed through this study that 99mTc-DC possessed high radiolabeling yield (95%). In vitro studies were performed by incubating 99mTc-DC in human serum at 37 °C. The in vitro binding interaction of the labeled antibiotic was analyzed with bacterial strain (live Staphylococcus aureus cells), and its stability was further determined. Moreover, for in vivo infection imaging study, the infection was induced with S. aureus (gram positive) cells intramuscularly injected in mice models followed by biodistribution studies for 99mTc-DC that were performed. Biodistribution studies of 99mTc-DC showed that the radiotracer was significantly accumulated at the site of infection and indicated the renal route of excretion. Scintigraphic images obtained as a result of in vivo study showed good uptake of prepared radiotracer (99mTc-DC) in the infectious lesions at 1-, 4-, and 24-h post-injection. Target-to-non-target ratios for 99mTc-DC were significantly different for the infectious lesions and non-infected tissues and remained 2.13 ± 0.3 up to 24-h post-injection of 99mTc-DC. 99mTc-DC showed preferential binding to living bacterial infected sites as compared to other parts of the body, and thus it can be inferred that 99mTc-DC might be a potential candidate to diagnose the infection.

Radioiodination of zearalenone and determination of Lactobacillus plantarum effect of on zearalenone organ distribution: In silico study and preclinical evaluation.

Purpose: Zearalenone (ZEN) which is one of the known fusarium species mycotoxin, produced primarily on many cereal crops. Consequently, the current study aims to estimate the possibility of labeling zearalenone and the pattern of accumulation of the produced labeled zearalenone [125I]-ZEN in different mice tissues, and the possible protective effect of Lactobacillus plantarum to reduce organ accumulation of Zearalenone. Materials and methods: the experiment was conducted on two groups of mice were used; the two groups received [125I] Zearalenone administered by tail vein injection, the first group receive nothing else while the second group received also L. plantarum (as a control agent) orally. The mice were kept under observation for 120 min to monitor zearalenone distribution. Results: by monitoring the zearalenone distribution the maximum concentration was found to be mainly primarily in the intestine (45.8 %) followed by the liver (27.15 %) while in the ovary (the most susceptible organ was (3.22 %) after120 min, in the first group of mice. The same pattern was observed in the second group with concentrations of (46.1 %), (30.19 %) and (0.09 %) in the intestine, liver respectively. Conclusion: These results indicated the lactic acid bacteria played a role in decreasing labeled zearalenone in the ovaries which is the target organ. [125I]-labeled ZEN is a promising novel tracer for organ imaging and that a significant role that L. plantarum could play in decreasing the zearalenone bioavailability of in mice organs.

Radioiodination of balsalazide, bioevaluation, and characterization as a highly selective radiotracer for imaging of ulcerative colitis in mice.

This work focuses on tracking ulcerative colitis in mice. High labeling yield and radiochemical purity were achieved for the formation of a [125/131 I]balsalazide radiotracer at optimum conditions of oxidizing agent content (chloramines-T [Ch-T], 75 µg), substrate amount (100 µg), pH of reaction mixture (6), reaction time (30 min), and temperature (37°C), using radioactive iodine-125 (200-450 MBq). The radiolabeled compound, [125/131 I]balsalazide, was stable in serum and saline solution during 24 h. Balsalazide is acting as a peroxisome proliferator-activated receptor (PPARγ). Biodistribution studies were carried in normal and ulcerated colon mice. High uptake of 75 ± 1.90% injected dose/g organ (ID/g) observed in ulcerated mice confirmed the suitability of [131 I]balsalazide as a novel radiotracer for ulcerative colitis imaging in mice.

Radiosynthesis and in silico bioevaluation of 131 I-Sulfasalazine as a highly selective radiotracer for imaging of ulcerative colitis.

This study demonstrated the tracking of ulcerative colitis, which is considered a stressful immune disease. Although there are many ways to test for this disease including dependence on gases, dyes, and painful anal endoscopy, these treatment modalities have many disadvantages. Hence, it is the utmost need of time to discover new methods to detect this chronic immune disease and to avoid the defects of traditional methodologies. Sulfasalazine (SSD) was labeled with iodine-131 (half-life: 8 days, Energy: 971 keV) under optimum reaction conditions including the amount of reducing agent, pH factor, chloramine-T (Ch-T) amount, and incubation period. Characterization was performed using 1 H/ 13 C-NMR, ESI-MS, and HPLC (UV/ Radio) techniques. The biodistribution study was performed in normal and ulcerative mice models, and in silico molecular docking study was performed to evaluate the possible mechanism of action to target peroxisome proliferator-activated receptor gamma (PPARγ). The high radiolabeling yield of [131 I]-sulfasalazine ([131 I]-SSD) was achieved ≥90% through the direct labeling method with radioactive iodine-131 in the presence of chloramine-T (100 µg). The radiotracer [131 I]-SSD was observed to be stable in normal saline and freshly eluted serum up to 12 hr at ambient temperature (37℃ ± 2℃). The radiotracer [131 I]-SSD showed the highest uptake in the targeted organ (i.e., ulcerative colon) which was observed to be ≥75% injected dose per gram (% ID/g) organ for 24 hr postinjection (p.i). Furthermore, in silico data collected from molecular modeling analysis of SSD and [131 I]-SSD with antimicrobial protein (PDB code: 3KEG) and peroxisome proliferator-activated receptor gamma (PPARγ) (PDB code: 4XTA) showed azoreductase activity and high binding potential for PPAR-γ site, respectively. The results of biological studies obtained in this study enlighten the usefulness of radiotracer [131 I]-SSD as a potential imaging agent for ulcerative colitis.

Tracing the protective activity of Lactobacillus plantarum using technetium-99m-labeled zearalenone for organ toxicity.

PURPOSE: Zearalenone is a potent estrogenic metabolite produced by some Fusarium and Gibberella species. Therefore, the aim of this study was to determine the accumulation of Technetium-[99m]-labeled zearalenone in mice organs as well as to study the protective effect of Lactobacillus plantarum. MATERIALS AND METHODS: Two different groups of mice were used; the first group of mice received Technetium-[99m]-zearalenone only, and the second group received both Technetium-[99m] zearalenone and L. plantarum (as a protective agent). Technetium-[99m]-labeled zearalenone was administered to mice by tail vein injection and L. plantarum was administered orally. Accumulation of labeled zearalenone in mice was monitored for 120 min. RESULTS: Labeled zearalenone was distributed primarily in the intestine (44.5%) and liver (20.12%) after 120 min in the first group of mice. In the second group of mice which received both Technetium-[99m] zearalenone and L. plantarum, labeled zearalenone was accumulated primarily in the intestine (46.8%) and liver (18.9%). These results indicated the decrease in labeled zearalenone in the liver due to the effect of lactic acid bacteria. CONCLUSION: Technetium-[99m]-labeled zearalenone can be used as a new tracer for organ imaging and that L. plantarum can decrease the bioavailability of zearalenone in mice organs.

Synthesis, characterization, radiolabeling and biodistribution of a novel cyclohexane dioxime derivative as a potential candidate for tumor imaging.

PURPOSE: Dioxime derivative is reported to exhibit high affinity towards tumor cells. The objective of the present study is to synthesize a new dioxime derivative to be labeled with technetium-99m for using as a solid tumor marker. MATERIALS AND METHODS: ((2E,2',3E,3')-3,3'-(cyclohexane-1,2-diylbis (azanylylidene)) bis-(butan-2-one)dioxime) was synthesized by condensation of Butan-2,3-dione monooxime and diaminocyclohexane and labeled with 99mTc. The in-vivo distribution of the agent was studied by carrying out biodistribution in tumor bearing Albino mice. RESULTS: A new cyclohexane dioxime derivative was synthesized with a good yield of 93 ± 2% and its complexation with 99mTc was prepared with 85 ± 4% radiochemical yield under the optimized conditions and the preparation exhibited in-vitro stability up to 6 h. Biodistribution studies showed high uptake in tumor cells with T/NT (target to non-target ratio) = 3.4 ± 0.2 after 0.5 h post injection. CONCLUSION: As a result of biodistribution studies, the newly synthesized cyclohexane dioxime derivative showed its good uptake in tumor cells, which affords a potential radiopharmaceutical that could be used as a good tumor imaging agent.

Radioiodinated esmolol as a highly selective radiotracer for myocardial perfusion imaging: In silico study and preclinical evaluation.

Challenges facing cardiovascular imaging necessitate innovation of better radiopharmaceuticals to augment or replace the existing ones. This research assesses the ability and competency of radioiodinated esmolol as a potential cardio selective imaging agent. Radioiodinated esmolol was synthesized with 97.3 ±â€¯0.3% radiochemical yield and with high stability up to 48 h at room temperature as well as in rat serum. Molecular modeling study was performed to confirm the binding of iodinated esmolol to ß1-adrenergic receptor. Its biodistribution studies in normal Swiss albino mice showed high heart uptake (38.5 ±â€¯0.11%ID/g at 5 min p.i.), heart/liver ratio nearly 3.85:1 and heart/lungs ratio was about 7:1 at 5 min p.i. The evidenced selectivity of the radioiodinated esmolol to ß1-adrenoceptor was confirmed by prior injection of cold esmolol. Gamma camera biodistribution pattern showed that radioiodinated esmolol accumulated selectively in heart.

Radioiodination and bioevaluation of rolipram as a tracer for brain imaging: In silico study, molecular modeling and gamma scintigraphy.

Brain imaging is considered one of the most fruitful applications of radioisotope scanning. Rolipram, a selective phospodiesterase-4 inhibitor, has been labeled using [125 I] with chloramine-T (Ch-T) as an oxidizing agent. Factors, such as the amount of substrate, pH, the amount of oxidizing agent, temperature, and the reaction time, have been systematically studied to optimize the iodination process. In addition, bio-distribution studies have indicated that the brain uptake of [125 I]iodorolipram is 7.6 ± 0.33 injected dose/g organ at 10 minutes post-injection, which cleared from the brain with time until it reaches 1.30 ± 0.17% at 1 hour post-injection. Therefore, iodorolipram could be considered as a potential, new selective radiotracer for brain imaging.

Radioiodination and biological evaluation of nizatidine as a new highly selective radiotracer for peptic ulcer disorder detection.

Nizatidine has been labeled using [125 I] with chloramine-T as oxidizing agent. Factors such as the amount of oxidizing agent, amount of substrate, pH, reaction temperature, and reaction time have been systematically studied to optimize the iodination. Biodistribution studies indicate the suitability of radioiodinated nizatidine as a novel tracer to image stomach ulcer. Radioiodinated nizatidine may be considered a highly selective radiotracer for peptic ulcer imaging.

Radioiodination and biological evaluation of candesartan as a tracer for cardiovascular disorder detection.

The goal of the study aims to evaluate newly radioiodinated candesartan (CAN) as a potential cardiovascular tracer. CAN was labeled using 125 I with chloramine-T (Ch-T) and N-bromosuccinimide (NBS) with full characterization of cold Iodo-candesartan. Factors such as pH, reaction temperature, reaction time, substrate, and oxidizing agent amounts were studied to optimize the radioiodination of CAN. The optimum radiochemical yield of 125 I-CAN was 98%. The labeled compound was separated and purified using high-pressure liquid chromatography. The biological distribution indicates the suitability of 125 I-CAN as a novel tracer to detect cardiovascular disorders.

An easy and effective method for synthesis and radiolabelling of risedronate as a model for bone imaging.

This study aimed to provide an easy method for synthesis of 1-hydroxy-2-(3-pyridyl) ethylidene bisphosphonic acid monosodium (sod. risedronate) with a high yield of 71%. The synthesized risedronate was labeled with technetium-99 m using two different reducing agents (SnCl2 .2H2 O and NaBH4 ) where NaBH4 gave stable complex and higher radiochemical yield more than SnCl2 .2H2 O. The results showed that, the radiochemical purity of (99m) Tc(NaBH4 )-risedronate was 99.2 ± 0.6% and its stability was up to 6 h. Biodistribution study showed high uptake and long retention of (99m) Tc(NaBH4 )-risedronate in bone starting from 15 min (29 ± 2.5% ID/organ) up to 4 h (35.1 ± 3.2 ID/organ) post injection. This research could introduce an easy and effective method for synthesis and labeling of risedrionate and affording a good tracer for bone imaging.