Synthesis, radiolabeling and evaluation of [99mTc][Tc-HYNIC/EDDA]-Met(O) as a early agent for amino acid metabolic imaging in C6 glioblastoma tumor.

Amino acid metabolism is recognized as a target for medical imaging due to its increase in malignant cells. Several radiotracers with primary achievement and possible subsequent chances have been designed and tested to image amino acid metabolism. Here, we report a new amino acid conjugate, with the purpose of extending [99mTc][Tc-HYNIC/EDDA]-Met(O) for single photon emission tomography (SPECT) imaging. The S-oxo-l-methionine (Met(O)) amino acid hydrazinonicotinamide (HYNIC) chelator conjugate (HYNIC-Met(O)) was prepared, using Fmoc solid-phase synthesis, and was radiolabeled with [99mTc]technetium pertechnetate, using tricine and ethylenediamine-N,N-diacetic acid (EDDA) as co-ligands. In vitro cellular uptake profile and saturation binding of radiotracer were determined on C6 glioma cells. Biodistribution and imaging studies were carried out on rat bearing C6 tumor tissue grafts. [99mTc][Tc-HYNIC/EDDA]-Met(O) was prepared in high yield and radiochemical purity (>98 %). The partition coefficient result showed that radioconjugate was very hydrophilic. The radioconjugate indicated both high cell uptake and in vitro internalization. Low nanomolar dissociation constant (66.02 nM) in C6 glioma cells was obtained for it as well. [99mTc][Tc-HYNIC/EDDA]-Met(O) revealed magnificent tumor uptake at early time points, with 1.98 ± 0.33 % injected activity per gram tumor (% IA/g) at 30 min post injection. The tumor uptake continued for 1 and 2 h and was 0.45 ± 0.33 % IA/g at 4 h. The uptake in other organs decreased much more rapidly causing high tumor to normal organ ratios so that the highest ratio of 13.25 of tumor-to-muscle at 60 min after injection was obtained with high contrast in gamma imaging. These results point out a very favorable [99mTc]Tc-labeled amino acid for targeting amino acid metabolism through target system L amino acid transporter (LAT1) in malignant cells especially C6 glioma cells. [99mTc][Tc-HYNIC/EDDA]-Met(O) manifests extremely good distribution, excretion and imaging attributes. So it seems to be an appropriate nominate for clinical imaging.

Inflammation scintigraphy imaging through a novel antimicrobial peptide labeled with technetium-99m in an animal model.

PURPOSE: Antimicrobial peptides (AMPs), due to their biological properties, have great potential for radiopharmaceutical development. In this research, a new antimicrobial peptide, derived from a 21-residue antimicrobial peptide microcinJ25 (MccJ25), was utilized to diagnose inflamed sites in mice bodies after labeling with [99mTc]Tc. MATERIALS AND METHODS: An antimicrobial peptide derivative was connected with an efficient chelator, hydrazinonicotinamide, and then labeled with [99mTc]Tc. The binding of labeled microcinJ25 conjugate to lymphocyte was investigated in vitro. Turpentine oil-induced inflammation uptake and tissue distribution were assessed through the animal pattern. Detector scanning was done through scintigraphy post injection of [99mTc]Tc-radiopeptide within different time points. RESULTS: High radiochemical purity (>98%) was obtained for [99mTc]Tc-radiopeptide. Lymphocyte binding assessment showed specific cell binding. Binding Inhibition was observed when additional unlabeled conjugate was used. In in vivo biological distribution studies, the uptake for inflamed tissue was 1.52 ± 0.12%ID/g. The inflammation site was visualized by scintigraphy imaging at 1 up to 2 hours. CONCLUSION: Based on our results this new designed [99mTc]Tc-radiopeptide was able to detect inflammation sites early and with high resolution, and could be considered a promising diagnostic candidate in inflammatory diseases.

The direct and indirect effects of bioactive compounds against coronavirus.

Emerging viruses are known to pose a threat to humans in the world. COVID-19, a newly emerging viral respiratory disease, can spread quickly from people to people via respiratory droplets, cough, sneeze, or exhale. Up to now, there are no specific therapies found for the treatment of COVID-19. In this sense, the rising demand for effective antiviral drugs is stressed. The main goal of the present study is to cover the current literature about bioactive compounds (e.g., polyphenols, glucosinolates, carotenoids, minerals, vitamins, oligosaccharides, bioactive peptides, essential oils, and probiotics) with potential efficiency against COVID-19, showing antiviral activities via the inhibition of coronavirus entry into the host cell, coronavirus enzymes, as well as the virus replication in human cells. In turn, these compounds can boost the immune system, helping fight against COVID-19. Overall, it can be concluded that bioactives and the functional foods containing these compounds can be natural alternatives for boosting the immune system and defeating coronavirus.

Effect of Persian and almond gums as fat replacers on the physicochemical, rheological, and microstructural attributes of low-fat Iranian White cheese.

The effect of Persian and almond gums (0, 0.1 and 0.2% (w/w)) as fat replacers and milk fat (0.4, 0.9, and 1.4% (w/w)) on physicochemical and rheological characteristics and microstructure of low-fat Iranian White cheese was studied. Persian and almond gums both effectively increased moisture-to-protein (M:P) ratio of low-fat cheese samples which in turn led to a significant reduction in the hardness parameters fracture stress and Young's and storage (G') moduli (p < .05); however, the effect of Persian gum was more pronounced (p < .01). Gum addition promoted cheese yield and proteolysis rate (p < .05). Response surface optimization described that supplementation of cheese milk containing 0.9% fat with 0.2% Persian gum and 0.12% almond gum would result in a low-fat cheese with textural properties similar to its full-fat counterpart. Scanning electron microscopy revealed that the fat replacers produced full-fat-like structure in the low-fat Iranian White cheese, when incorporated at the optimum levels.

Short communication: Effect of whey protein addition and transglutaminase treatment on the physical and sensory properties of reduced-fat ice cream.

The effects of whey protein addition and transglutaminase treatment, alone and in combination, on the physical and sensory properties of reduced-fat ice cream were investigated. Adding whey protein with or without enzyme treatment decreased melting rate, overrun, and hardness of the reduced-fat ice cream; however, the enzyme-treated sample had a higher melting rate and overrun and softer texture. Whey protein-fortified samples showed higher melting resistance, but lower overrun and firmer texture compared with the enzyme-treated sample without added whey protein. Whey protein addition with or without transglutaminase treatment caused an increase in apparent viscosity and a decrease in flow index of the reduced-fat ice cream; nevertheless, the flow behavior of full-fat sample was most similar to the enzyme-treated reduced-fat sample with no added whey protein. Descriptive sensory analyses showed that neither whey protein addition nor transglutaminase treatment significantly influenced the flavor and odor of reduced-fat ice cream, but they both noticeably improved the color and texture of the final product. The results of this study suggest that whey protein addition with transglutaminase treatment improves the physical and sensory properties of reduced-fat ice cream more favorably than does whey protein addition or transglutaminase treatment alone.

Preparation and biological evaluation of [(99m)Tc/EDDA/Tricine/HYNIC(0), BzThi(3)]-octreotide for somatostatin receptor-positive tumor imaging.

Somatostatin-derived analogues play an important role in the diagnosis and treatment of neuroendocrine tumors. The aim of this study was to evaluate a new somatostatin analogue designed for labeling with (99m)Tc: [6-hydrazinopyridine-3-carboxylic acid (HYNIC(0)), ß-(3-benzothienyl)-Ala (BzThi(3))]-octreotide ([HYNIC]-BOC), using ethylenediamine-N,N'-diacetic acid (EDDA) and tricine as coligands. Synthesis was performed on a solid phase using a standard Fmoc strategy. The HYNIC-peptide conjugate was radiolabeled with (99m)Tc and characterized by ITLC and high-performance liquid chromatography (HPLC). In vitro studies were carried out in sstr2 expressing AR4-2J cell lines. In vivo distribution studies were performed in rats bearing the AR4-2J tumor. The radiolabeled complex could be prepared at high-specific activities and >95% radiochemical yield as determined by HPLC. The peptide conjugate showed high-affinity binding for sstr2. The radioligand showed high and specific internalization into AR4-2J cells (18.19%±0.21% at 4 hours). In vivo distribution studies in rats bearing tumor have shown a receptor-specific uptake of radioactivity in somatostatin receptor-positive organs. After 4 hours, uptake in the AR4-2J tumor was 1.71%±0.36% injected dose per gram tissue (%ID/g). These data show that [(99m)Tc/EDDA/Tricine/HYNIC(0), BzThi(3)]-octreotide is a specific radioligand for the somatostatin receptor-positive tumors and is a suitable candidate for clinical studies.

Clinical evaluation of antimicrobial peptide [(99m)Tc/Tricine/HYNIC(0)]ubiquicidin 29-41 as a human-specific infection imaging agent.

INTRODUCTION: Ubiquicidin (UBI) 29-41 is a cationic synthetic antimicrobial peptide fragment that binds preferentially with the anionic microbial cell membrane at the site of infection. This study was conducted to evaluate the potentiality of [(99m)Tc/Tricine/HYNIC(0)]UBI 29-41 prepared from lyophilized kits as an infection imaging agent in humans. METHODS: Seven patients (5 males and 2 females; mean age=55 years; age range=35-75 years) with suspected bone or soft-tissue infections participated in this study. [(99m)Tc/Tricine/HYNIC]UBI 29-41, corresponding to activity in the range 555-740 MBq added to 40 mug of peptide obtained from instant freeze-dried kit formulations with radiochemical purities >95%, was injected intravenously. A 45-min dynamic study was followed by spot views of the suspected region of infection (target) and a corresponding normal area (nontarget). Whole-body anterior and posterior images were also acquired at 30, 60 and 120 min after injection. True- or false-positive or true- or false-negative images were interpreted upon bacterial culture, radiography, clinical tests and bone scanning. RESULTS: The biodistribution of [(99m)Tc/Tricine/HYNIC]UBI 29-41 in patients showed rapid accumulation of activity in the kidneys in the first 30 min after injection that gradually declined and accumulated in the urinary bladder. There were positive findings in five studies and negative findings in two. Findings were subsequently confirmed to be true positive or negative. Images showed minimal accumulation in nontarget tissues, with an average target/nontarget ratio of 2.10+/-0.33 in positive lesions at 30 min. CONCLUSION: Given its favorable clinical characteristics, [(99m)Tc/Tricine/HYNIC]UBI 29-41 shows promise as a tracer for infection imaging that allows early diagnosis (30 min) of infection.