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Gold nanoparticles (AuNPs) represent very attractive and promising drug delivery carriers due to their unique dimensions, adjustable surface functions, and controllable drug release. Therefore, AuNPs are used to overcome the limitations of conventional chemotherapy, for example methotrexate (Mex), one of the first-generation chemotherapy drugs for cancer treatment, whose usefulness has been restricted due to drug resistance and dose-dependent side effects. In the present study, the AuNPs drug delivery system was synthesized and loaded with technetium-99 m radiolabeled Methotrexate (99mTc-Mex) to produce new potential nanoradiopharmaceutical for tumor targeting and further imaging. The Methotrexate loaded gold nanoparticles (Mex-AuNPs) successfully prepared in small spherical particle size (20.3 nm), polydispersity index PDI ( 90 %. The preclinical biodistribution studies of 99mTc-Mex-AuNPs were performed in 3 experimental groups A (intravenous (I.V.) injected normal mice), B and C (I.V. and intratumor (I.T.) injected tumor bearing mice, respectively). The 99mTc-Mex-AuNPs achieved highest tumor uptake (93 ± 0.39 %ID/g) and highest Target/NonTarget (T/NT) ratio (58.1 ± 0.91) with high Tumor/Blood (T/B) ratio (25.8 ± 0.11) at 10 min post I.T. injection and retained high tumor uptake (79 ± 0.65 %ID/g) up to 60 min post I.T. injection before escaping into blood stream. Consequently, 99mTc-Mex-AuNPs can be considered as new potential nanoradiopharmaceutical in tumor diagnosis.

This study was designed to biosynthesize Aspergillus flavus copper oxide NPs (AFCuONPs) using extracellular fungous filtrate technique and evaluating its medical importance. AFCuONPs were successfully biosynthesized with average size of 32.4 nm and zeta potential of – 36 mV. They were fully characterized using FT-IR, UV–Vis spectrophotometry, and TEM. AFCuONPs cytotoxicity and bactericidal activity were evaluated against different cell lines and pathogenic bacteria, respectively. [99mTc]Tc-AFCuONPs were radiosynthesized with high radiolabeling yield (93 ± 0.85%). In vivo biodistribution of [99mTc]Tc-AFCuONPs in tumor-bearing mice model showed high tumor uptake. These results introduce AFCuONPs as a promising medical agent.

The [99mTc]Tc-Doxorubicin–Gold Nanoparticles (99mTc-Dox-AuNPs) was formulated as a nanoradiopharmaceutical by different loading procedures to enhance tumor targeting. The formula F1 that was prepared by direct loading of pre-prepared [99mTc]Tc-Doxorubicin showed a reasonable in-vitro characterization values, high entrapment efficiency (92 ± 0.72%), acceptable in vitro release data and convenient in-vitro serum stability up to 24 h. F1 presented high tumor uptake (54%ID/g) with high Target/ Non Target (T/NT) ( ≈ 77) and Drug Target Efficiency percent (%DTE) above 100% at 0.5 h via intra-tumoral injection that prove the increasing of tumor targeting and in-vivo stability by direct loading for pre-prepared [99mTc]Tc-Doxorubicin.

The current work represents the design and synthetic approaches of a new set of compounds 6–10 bearing the 1,4-dimethyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide scaffold. The biological evaluation revealed that most of the new compounds were promising selective dipeptidyl peptidase-IV (DPP-4) inhibitors and in vivo hypoglycemic agents utilizing linagliptin as a standard drug. The acute toxicity examination confirmed the safety profile of all compounds. Molecular docking studies related the significant DPP-4 suppression activity of compounds 9a, 10a, 10f, 10g to their nice fitting in the active pocket of DPP-4. In addition, the molecular dynamic study exhibited the stability of both 10a and 10g within the active site of DPP-4. The QSAR study showed that the difference between the predicted activities is very close to the experimental suppression effect. Moreover, both compounds 10a and 10g obeyed Lipinski's rule, indicating their efficient oral bioavailability. Compound 10a was radiolabeled, forming the 131I-SQ compound 10a to study the pharmacokinetic profile of this set of compounds. The biodistribution pattern hit the target protein since the tracer accumulated mainly in the visceral organs where DPP-4 is secreted in a high-level, thus with consequent stimulation of insulin secretion, leading to the target hypoglycemic effect.

This study aimed to synthesize a nano-structure between selenium, Vit. C, and Vit. E (Vit-E/C@SeNPs) as a promising protective and therapeutic agent for hepatocellular carcinoma. Vit-E/C@SeNPs were characterized using TEM and DLS and its zetapotential was measured to evaluate its stability. DPPH assay and SRB test were performed to estimate its antioxidant capacity and cytotoxicity, respectively. A radiosynthesis of 99mTc-Vit-E/C@SeNPs was done for further in-vivo pharmacokinetic studies on normal and solid tumor induced mice. Further, in-vivo studies were conducted to investigate Vit-E/C@SeNPs efficacy against hepatocellular damage in Wistar albino rats induced by diethylnitrosamine (DEN) / Carbon Tetra chloride (CCl4). The synthesis results showed spherical Vit-E/C@SeNPs with core size of 50 nm, radical scavenging activity (%RSC) of 75.9%, and IC50 of 27.9 µg/ml. The biochemical analysis results showed that the lower liver function biomarker values (ALT, AST, ALP, total bilirubin and GGT) has gone for the Vit-E/C@SeNPs prevention and treated group, which also showed significant depletion of liver tissue l -MDA, and obvious increase in GSH concentration and CAT activity and marked improvement in the histological feature of liver tissue. Additionally, a significant up-regulation of mRNA gene expression levels of inflammatory gene (TGFβ1, NFκB, iNOS, PPAR-γ and TNFα) and Apoptotic gene (P53) were determined by using Quantitative real-time PCR (qPCR). The values down regulate and tend to normal in prevention and control group. All of these introduce Vit-E/C@SeNPs as a promising agent as protective and therapeutic agent against DEN/ CCl4-induced hepatocellular damage (Hepatocellular carcinoma).

Graphene is a crystalline form of carbon that is regarded as a novel and innovative product. carboxylated nanographene oxide sheets (NGO-COOH) was synthesized using a modified Hummer's method and assess their medical significance. NGO-COOH were successfully synthesized with an average size of 40 nm. FT-IR, UV–Vis, XPS spectrophotometry, and TEM were used to thoroughly describe them. The cytotoxicity function of NGO-COOH nanosheets were tested against cell line. The radiosynthesized [99mTc]Tc-NGO-COOH had a high radiolabeling yield (97.3±0.45 %). The tumor uptake of [99mTc]Tc-NGO-COOH nanosheets in an in vivo biodistribution model in tumor-bearing mice was high. NGO-COOH nanosheets may be a promising imaging agent, based on these findings.

PURPOSE: Oral administration of Iodine(−131) (I(−131)) solutions causes high risk of contamination for patients and dispensers. The objective of the study was to adapt hard gelatin capsules (HGCs) for filling with radiopharmaceutical solutions without deformation. METHODS: Polystyrene (PS) internally lining films with different thicknesses were used to protect HGCs. The insulated HGCs were evaluated for their physicochemical characteristics and rupturing time in different dissolution media. HGCs internally lined with PS were examined for withstand loading with different volumes and radioactivities of I(−131) solutions. Radioactivity release was studied in deionized water and acidic media. Quality control of released I(−131) was inspected for radiochemical purities. RESULTS: There was a directly proportion between PS lining thickness and stability of HGCs after filling with 500 μl aqueous methylene blue solution. HGCs internally lined with PS 100 μm thickness withstand deformation for ˃ two months; however showed fast in-vitro rupturing time in different dissolution media. Internally lined HGCs loaded with different volumes and radioactivities of I(−131) solutions resisted for one week without radioactive leakage. Yet, revealed complete release of I(−131) after 20 min in dissolution media with great radiochemical purity. CONCLUSION: The study promises safely I(−131) aqueous solution delivery via adapted HGCs. [Figure: see text]

Curcumin is a polyphenol extracted from Curcuma longa, used as a spice, in food coloring, and as a traditional herbal medicine. It has wide therapeutic platform as anti-oxidant, anticancer, anti-inflammatory and anti-infection properties. This review discusses the analytical methods used in determination of curcumin in various matrices with degradation profile, expected degradation products and stability tests.

Selenium nanoparticles (SeNPs) have become one of the most prospective and promising tools in the course of cancer diagnosis and therapy. Here we describe the synthesis of a novel radioactive platform for tumor imaging using selenium nanoparticles. SeNPs were synthetized using dithionite and glutathione as reducing and capping agent respectively with 5 mmol/L sodium selenite as a precursor and then SeNPs radiolabeled with technetium-99 m, the most common and famous radioactive isotope used for imaging purposes. A characteristic profile for the synthesized SeNPs was performed including size analysis, zeta potential, antioxidant activity, radiochemical yield and in-vivo biodistribution in normal and solid tumor bearing mice. Size analysis showed amorphous SeNP cores of a mean diameter of 21 ± 5 nm with a hydrodynamic size of 43 ± 8 nm and −28 mV zeta potential. The particles also showed a superior antioxidant activity of radical scavenging activity 55.6% according to DPPH assay, in addition, satisfying radiochemical yield up to 97 ± 1.5 was achieved. In vivo studies were applied on male Swiss albino mice that demonstrated a good biodistribution pattern in normal mice with a moderate accumulation in liver at 30 min post injection. Excellent T/NT ratios were obtained in solid tumor bearing mice throughout the experimental time points. The as-synthetized selenium nanoparticles demonstrated surprising and satisfying features which make them promising enough for tumor theranosis.

We report herein an innovative approach to prostate tumor therapy using tumor specific radioactive gold nanoparticles (198Au) functionalized with Mangiferin (MGF). Production and full characterization of MGF-198AuNPs are described. In vivo therapeutic efficacy of MGF-198AuNPs, through intratumoral delivery, in SCID mice bearing prostate tumor xenografts are described. Singular doses of the nano-radiopharmaceutical (MGF-198AuNPs) resulted in over 85% reduction of tumor volume as compared to untreated control groups. The excellent anti-tumor efficacy of MGF-198AuNPs are attributed to the retention of over 90% of the injected dose within tumors for long periods of time. The retention of MGF-198AuNPs is also rationalized in terms of the higher tumor metabolism of glucose which is present in the xanthanoid functionality of MGF. Limited/no lymphatic drainage of MGF-198AuNPs to various non-target organs is an attractive feature presenting realistic scope for the clinical translation of MGF-198AuNPs in for treating prostate cancers in human patients. The comparative analysis of MGF-198AuNPs with other radioactive gold nanoparticles, functionalized either with epigallocatechin gallate or the Gum Arabic, has revealed significantly superior tumoricidal characteristics of MGF-198AuNPs, thus corroborating the importance of the tumor-avid glucose motif of MGF. Oncological implications of MGF-198AuNPs as a new therapeutic agent for treating prostate and various solid tumors are presented.

Purpose: Ifosfamide as a chemotherapeutic drug is used for the treatment of different cancer types. The purpose of this study is the preparation of 99mTc-ifosfamide complex to be evaluated as a pot...

Selenium is one of the most important dietary supplements in the human diet. It is incorporated into the synthesis of many antioxidant proteins, which serve as scavengers of reactive oxygen species such as glutathione peroxidase. Therefore, selenium has become antagonistic and resistant to many diseases resulting from oxidative stress such as arthritis, tumors, and heart and brain diseases. Selenium nanoparticles (SeNPs) have the potential to serve as new nutritional supplements with higher degradability, lower toxicity and ability to be cleared gradually from the body. Selenium nanoparticles have emerged as unusual selenium species with amazing prophylactic and therapeutic properties with dual synergistic effects of providing therapeutic cargo and improved anticancer activity. Recent investigations have also explored new applications of nano-scaled forms of selenium for a wide range of biological activities such as antibacterial and antifungal agents. Herein, we provide a focused account on the recent advances on various biomedical applications of selenium nanoparticles with a particular emphasis on their chemistry, nanotechnology and various applications in life sciences.

Non-invasive molecular imaging techniques are accruing more interest in the last decades. Several radiolabelling elements have been FDA-approved and are currently used to characterize tumors. In this study, the DNA intercalating agent doxorubicin was radiolabelled with 125I. Several parameters for the radiolabelling reaction were investigated and optimized. A maximum yield of 94 ± 0.3% was reached after reacting 20 μg of doxorubicin with 200 μg Chloramine-T at pH 5 for 30 min. The in vivo stability of 125I-doxorubicin is validated by the low propensity for thyroid uptake in mice. The preclinical T/NT ratio was approximately 6.4 at 30 min. Docking and molecular dynamics confirmed that the radiolabelling of doxorubicin did not affect (or slightly improved its binding to DNA). Overall, 125I-doxorubicin was demonstrated to be a promising non-invasive probe for solid tumor imaging.

Virus infections are an increasing and probably lasting global risk. Nucleoside and nucleotide analogs represent the largest class of antiviral drugs. Early success in the treatment of human immunodeficiency virus infection and the recent approval of sofosbuvir as phosphoramidate nucleoside prodrug for chronic hepatitis C have provided proof of concept for important this class of compounds as an antiviral agent. This review summarizes the antiviral activity of nucleoside and nucleotide analogs and their recent application.

The aim of the presented study is to investigate a new promising radiopharmaceutical tracer able to visualize and differentiate inflammation versus infection in early stages. Radioiodinated tenoxicam ( 125 I-tenoxicam) was prepared and its radiochemical yield and in vitro stability were assayed. The biodistribution studies were conducted on two different mice models: sterile inflammation and bacterial infection mice models. 125I-tenoxicam showed high T/NT accumulation in the inflammatory tissues revealing high selectivity to the inflammatory tissues in contrast to infection bearing mice. The docking study using CDOCKER protocol for tenoxicam and radioiodinated tenoxicam with COX enzymes was performed to confirm that radioiodinated tenoxicam still retaining COX enzymes selectivity.

Stem cells are undifferentiated cells with a potential to be developed into different types of body cells. Stem cells are used in regenerative medicine as a repair system that is working to restore the structures and functions of damaged tissues and organs aiming to find a way to cure untreatable injuries and diseases. Stem cell-nanotechnology hybrid is the application of nanotechnology in stem cells research. One of the most interesting applications is the biocompatible magnetically-responsive nanoparticles (NP) that are being utilized for the targeted delivery of stem cells; in order to enhance their retention in the desired treatment site. This review provides an overview of stem cells therapy based on nanotechnology for the treatment of different diseases, such as: peripheral artery disease (PAD), myocardial infarction (MI), atherosclerosis, Huntington's disease, spinal cord injury (SCI), Alzheimer disease (AD), diabetes mellitus (DM), multiple sclerosis (MS), erectile dysfunction (ED), and cancer diseases.

The current study is aimed to prepare 99mTc-lidocaine as a new myocardial perfusion-imaging agent. The used 99mTc was obtained from Al–99Mo-molybdate(VI) gel matrix. 99mTc-lidocaine showed higher (15.4 ± 0.11% ID/g) and faster (15 min post injection) cardiac uptake than the recently studied 99mTc-valsartan and 99mTc-procainamide. Consequently, 99mTc-lidocaine will be a valuable myocardial SPECT agent for diagnosis of emergency patients. Besides, the receptor affinity study confirmed the selectivity of 99mTc-lidocaine for sodium channels in the heart.

Several novel thiazolidinone and fused thiazolidinone derivatives bearing benzenesulfonamide moiety were synthesized and confirmed via spectral and elemental analyses. The newly synthesized compounds were evaluated for their cytotoxic activity on colorectal cancer cell line (Caco-2). All the synthesized compounds showed better activity than the reference standards (Doxorubicin and 5-FU). Investigation of the apoptotic activity of the most active compounds revealed that compounds 3a, 5a, 5c and 6c activate both caspase-3 and Fas-ligand in Caco-2 cell line. Compound 3a was the most active compound with caspase-3 concentration of 0.43 nmol/mL and Fas-ligand concentration of 775.2 pg/mL in treated Caco-2 cells. Compound 3a was radiolabeled with 99mTc and its biodistribution pattern was evaluated in vivo using normal Swiss Albino mice. 99mTc-compound 3a complex didn't exhibit any accumulation in any body organs except for its accumulation in the colon; target organ; where it showed 8.97 ± 1.35 %ID/g at 15min p. i. that elevated till 16.02 ± 2.43 %ID/g at 120min p. i.

The purpose of our study was to improve the delivery of a direct-acting antiviral drug, daclatasvir, to the site of action, liver tissues, using physically and biologically stable cationic bile-based vesicles. Accordingly, cationic bile-based vesicles were prepared as pro-bile-based vesicles and diethylaminoethyl dextran (DEAE-Dx)-stabilized bile-based vesicles to increase their stability without negatively affecting their hepatic affinity. The prepared bile-based vesicles were characterized for particle size, polydispersity index, ζ-potential, in vitro daclatasvir release, and ex vivo permeation using non-everted gut sac intestine. The in vivo biodistribution was experimented after oral administration utilizing the radiolabeling assay, where the liver showed the highest accumulation of the DEAE-Dx-stabilized bile-based vesicles after 4 h, reaching a value of 4.6% ID/g of the total oral administered dose of the labeled drug compared to drug solution, pro-bile-based vesicles, and cationic bile-based vesicles where the accumulation was 0.19, 1.3, and 0.31% ID/g, respectively. DEAE-Dx-stabilized bile-based vesicles increased the drug deposition into the liver about 42-fold compared to oral solution. The high physical stability and the high resistance to opsonization and clearance show that DEAE-Dx-stabilized bile-based vesicles could be efficiently applied for enhancing daclatasvir delivery to the liver after oral administration.

A new series of thiazolidinone (5a-g), thiazinone (9a-g) and dithiazepinone (9a-g) heterocycles bearing a benzenesulfonamide scaffold was synthesized. Cytotoxicity of these derivatives was assessed against MCF-7, HepG2, HCT-116 and A549 cancer cell lines and activity was compared to the known cytotoxic agents doxorubicin and 5-FU where the most active compounds displayed better to nearly similar IC50 values to the reference compounds. For assessing selectivity, the most active derivatives against MCF-7, 5b, 5c and 5e, were also assessed against the normal breast cell line MCF-10 A where they demonstrated high selective cytotoxicity to cancerous cells over that to normal cells. Further, the effect of the most active compounds 5b-e on MCF-7 and HepG2 cell cycle phase distribution was assessed and the tested sulfonamide derivatives were found to induce accumulation of cells in the

The development of cancer theranostic nanomedicines is recommended to concurrently achieve and evaluate the therapeutic benefit and progress. The current work aims to develop gallic acid-gold nanoparticles (GA-Au NPs) as a theranostic probe for 99mTc-Doxorubicin (99mTc-DOX) based on the spatiotemporal release pattern induced intra-tumoral (IT) delivery. DOX-loaded GA-Au NPs were developed and identified via UV–Vis spectroscopy. The system was characterized for drug loading efficiency%, particle size, zeta potential, topography, in vitro DOX release and anti-proliferative activity against the MCF-7 cell-line. The factors influencing radiolabeling efficiency of DOX with 99mTc (DOX concentration, stannous chloride concentration, reaction time and pH) were optimized. The in vitro stability in mice serum and in vivo distribution studies in mice of 99mTc-DOX-loaded GA-Au NPs were investigated following IV and IT administration. Dox-loaded GA-Au NPs had a loading efficiency of 91%, a small particle size (≈50 nm), a promising zeta potential (−20 mV) and a sustained drug release profile at pH 5.3. GA-Au NPs exhibited increased anti-proliferative activity, with approximately a four-fold lower IC50 value (0.15 μg/ml) than free DOX. The optimized radiolabeling efficiency of 99mTc-DOX was ≈93%. It showed good physiological stability in mice serum for at least 8 h. The IT delivery of 99mTc-DOX-loaded GA-Au NPs in tumor-induced mice showed dramatic tumor accumulation. A maximum magnitude of 86.73%ID/g was achieved, at 15 min post-injection, with a target/non-target ratio of ≈56. 99mTc-DOX-loaded GA-Au NPs could be used for the selective IT delivery of a chemotherapeutic agent and an imaging agent to a target organ.

Gold nanoparticles are currently used for the treatment of cancer through a myriad of modalities and delivery approaches. Conjugation of tumor imaging Single Photon Emitting Computed Tomographic (SPECT) radiopharmaceutical to gold nanoparticles will allow systemic targeting and imaging of cancer tissues simultaneously. In this study, gold nanoparticles (AuNPs) were prepared using Epigallocatechingallate (EGCG), loaded with doxorubicin (Dox), and characterized before and after doxorubicin conjugation. Cytotoxicity of EGCG-AuNPs and Dox-EGCG-AuNPs were evaluated against breast carcinoma (MCF-7) and hepatocellular carcinoma (HepG-2) cell lines demonstrating high cytotoxic effects of Dox-EGCG-AuNPs against both cell lines. Doxorubicin was radiolabeled with 99mTc and our new approach has optimized various labeling conditions resulting in a radiochemical yield of 93.5 ± 2.04%. Biodistribution of 99mTc-Dox-EGCG-AuNPs was studied in normal and tumor bearing mice following I.V. and intratumoral injections at different time intervals. Results showed high uptake of the intravenously injected 99mTc-Dox-EGCG-AuNPs in tumor tissue (22.45 %ID/g at 2 h). In addition, localized intratumoral injection of 99mTc-Dox-EGCG-AuNPs showed extremely high levels of uptake in tumor (80.22 %ID/g at 15 min) with high retention for extended periods post injection. Our results present prospects for the utility of 99mTc-Dox-EGCG-AuNPs as a multiplexed theranostic agent through SPECT imaging of tumor tissue and therapy through photothermal destruction of cancer tissue through the application of exogenous laser lights as well as through tyrosine phosphatases inhibitor (through EGCG), and topoisomerase II inhibitor (through doxorubicin) effects.

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 ± 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 β1-adrenergic receptor. Its biodistribution studies in normal Swiss albino mice showed high heart uptake (38.5 ± 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 β1-adrenoceptor was confirmed by prior injection of cold esmolol. Gamma camera biodistribution pattern showed that radioiodinated esmolol accumulated selectively in heart.

This study describes the preparation of radioiodinated anastrozole and epirubicin and their biological evaluation as potential solid tumor imaging gents. Radioiodinated anastrozole and epirubicin were successfully prepared via direct electrophilic substitution reaction at ambient temperature. The radiochemical yields for radioiodinated anastrozole and epirubicin were maximized to 92.9 ± 0.1 and 98.8 ± 0.1 %, respectively by studying different reaction parameters such as substrate amount, chloramine-T, pH of the reaction mixture, reaction temperature and reaction time. They showed in vitro stability up to 4 and 24 h, respectively. The preclinical evaluation and biodistribution in mice bearing solid tumor showed high retention and biological accumulation in solid tumor cells (12.4 and 25.3 % injected activity/g tissue) and high T/NT ratio equal to 4.7 ± 0.1 and 5.2 ± 0.1 at 2 and 1 h post-injection, respectively. Data described before could recommend radioiodinated anastrozole and radioiodinated epirubicin as potential targeting radiopharmaceuticals for solid tumor imaging.

Acebutolol was successfully labeled with (125) I via direct electrophilic substitution reaction. Radioiodinated acebutolol was prepared with a maximum radiochemical yield of 96.5 ± 0.3% and in vitro stability up to 72 h. The in vivo biological distribution of radioiodinated acebutolol showed high heart uptake of 37.8 ± 0.14% injected activity/g organ with low lungs and liver uptakes at 5 min post-injection. In vivo receptor blocking study was carried out in mice to evaluate its selectivity to heart. Radioiodinated acebutolol showed fast heart accumulation with high heart/liver ratio, which provides the ability for fast myocardial imaging with significant decrease in the radiation hazards risk on patients. So, radioiodinated acebutolol could be displayed as a radiotracer drug of choice in case of emergency patients for myocardial perfusion imaging.

Radioiodinated fenoterol and reproterol were prepared by electrophilic radioiodination reaction using chloramin-T as oxidizing agent with radiochemical yields of 97.7 ± 0.7 and 95.2 ± 0.3 %, respectively, and in vitro stability up to 72 h. Biodistribution study performed in male Albino Swiss mice showed maximum radioactivity accumulation in lungs tissue to the extent of 52 ± 1.03 and 50.6 ± 1.2 % ID/g at 15 and 30 min post injection (p.i.) for radioiodinated fenoterol and reproterol, respectively, with low accumulation in heart and blood. The clearance pathway of both iodo-compounds was through renal and hepatobiliary routes. The selectivity of iodo-compounds to lung was examined by in vivo receptor blocking study. Radioiodinated fenoterol and reproterol are not a blood products and so they are more safer than the currently available 99mTc-MAA, and their lungs uptake is higher than that of the recently discovered 125/123I-IPMPD, 99mTc(CO)5I, 99mTc-DHPM and 125/123I-paroxetine. So, radioiodinated fenoterol and reproterol could be introduced as a new compromising radiopharmaceuticals for lung perfusion scintigraphy more safe than the currently available 99mTc-MAA and more potential than the recently discovered 125/123I-IPMPD, 99mTc(CO)5I, 99mTc-DHPM and 125/123I-paroxetine.

The goal of this study was to biologically evaluate a newly synthesized radioiodinated ethyl 1,4-dihydro-7-iodo-4-oxoquinoline-3-carboxylate (EIOQC) as a potential lung scintigraphic agent. EIOQC was synthesized, characterized then radioiodinated via direct electrophilic substitution reaction. Factors affecting the radiochemical purity were studied in details and the biological distribution of the radioiodinated compound was evaluated in normal male Albino mice. EIOQC was successfully synthesized and radioiodinated with high radiochemical purity (96 ± 1.21 %) and in vitro stability up to 48 h. The biological evaluation of radioiodinated EIOQC showed high lung affinity of 21.36 ± 1.73 % injected dose/g organ (% ID/g) at 15 min. This study introduces radioiodinated EIOQC as a novel potential radiopharmaceutical for lung perfusion scintigraphy.

The aim of this study is the formulation of a new radiopharmaceutical for imaging solid tumor bearing. Gemcitabine is a nucleoside analogue used as chemotherapeutic agent. Gemcitabine was formulated and radiolabeled with one of the most important diagnostic radioactive isotopes (technetium-99m) to be investigated in solid tumor imaging. The labeling parameters such as gemcitabine amount, stannous chloride amount, pH of the reaction mixture, and reaction time were optimized. 99mTc–gemcitabine was prepared at pH 9 with a maximum labeling yield of 96 ± 0.3 % without any notable decomposition at room temperature over a period of 8 h. The preclinical evaluation and biodistribution in solid tumor bearing mice showed that 99mTc–gemcitabine had solid tumor selectivity, preclinical high biological accumulation in tumor cells and high retention. Tumor/normal muscle (T/NT) ratios increased with time showing high T/NT ratio (T/NT = 4.9 ± 0.27 at 120 min post injection) and high Tumor/Blood ratio (3.4 ± 0.06), suggesting 99mTc–gemcitabine as a novel solid tumor imaging agent.

Radioiodinated N-(3-iodophenyl)-2-methylpyrimidine-4,6-diamine (radioiodinated IPMPD), a potential lung scintigraphic agent, was synthesized via direct electrophilic substitution. Factors affecting the radiochemical yield were studied in detail. High radiochemical yield (92.3 ± 2.3%) was reached. The compound is stable in vitro for 24 h. Radioiodinated IPMPD was biologically evaluated in normal Albino mice. The compound demonstrated high lung uptake (21.4 ± 1.7% of injected dose per gram organ at 15 min) and thus shows promise for lung perfusion scintigraphy.

Tyrosine kinases are groups of enzymes, which are over-expressed in solid tumor cells, representing good targets for different drugs such as sunitinib (N-[2-(diethylamino)ethyl]-5-{[(3Z)-5-fluoro-2-oxo-2,3-dihydro-1H-indol-3-ylidene]methyl}-2,4-dimethyl-1H-pyrrole-3-carboxamide). The aim of this work was to design and synthesize (99m)Tc-sunitinib radiotracer and to study its tumor binding specificity as a novel selective radiopharmaceutical for tumor hypoxia imaging. The in vivo biodistribution of (99m)Tc-sunitinib in tumor bearing mice showed high target/non-target (T/NT) ratio (T/NT ~ 3 at 60 min post injection). This preclinical high biological accumulation in tumor cells suggests that (99m)Tc-sunitinib is ready to go through the clinical trials as a potential selective radiotracer able to image tumor hypoxia.

Non-invasive quantification of myocardial β-receptors could become an independent prognostic marker for chronic heart failure and cardiovascular disorders. The aim of this study was to formulate a novel radiopharmaceutical for the detection of myocardial infarction at early stages in susceptible patients, which requires the development of high myocardium affinity radiopharmaceuticals able to establish an accurate in vivo quantification of cardiac β1-adrenoceptors. This was attained by the direct complexation of nebivolol as a cardioselective agent with technetium-99m as one of the most useful radionuclides in diagnostic nuclear medicine. Factors affecting the radiochemical yield such as nebivolol amount, stannous chloride amount, reaction time and pH of the reaction mixture were optimized. The results showed that the radiochemical yield was 95 ± 2.87 % and the radiolabeled compound was separated by high performance liquid chromatography. In vitro studies showed that the formed complex was stable for up to 24 h. In vivo uptake of 99mTc-nebivolol in the heart was 4.55 ± 0.23 % ID/g organ at 0.5 h post injection, whereas the clearance from Albino mice appeared to proceed via the hepatobiliary and renal clearance pathways. Predosing mice with cold nebivolol reduced the heart uptake to 1.1 ± 0.02 % and further confirmed the high specificity and selectivity of this radiotracer for the assessment of the myocardial β1-adrenoceptors.

Meropenem was successfully radiolabeled with 99mTc in high labeling yield (92 ± 2%) and stability (~6 h). 99mTc–meropenem showed high accumulation in tumor hypoxic tissue (4.193% injected dose/g organ). 99mTc–meropenem showed high ability to differentiate the tumor tissue from inflamed or infected tissues in different mice models as its T/NT ratio ~4 in case of tumor mice model while T/NT ratio ~1 in case of inflamed mice model. So, 99mTc–meropenem showed high selectivity in comparison with FDG-PET and 99mTc-nitroimidazole analogues. Thus, 99mTc–meropenem could be used as a selective potential imaging agent for diagnosis of tumor hypoxia.

The detection of bone metastasis in early stages requires the development of high-affinity bone imaging radiopharmaceuticals for the improvement of the diagnostic accuracy of routine bone scanning and effective management of these medical cases. This study aimed to provide a convenient synthesis of 1-thioethylidene-l,l-disodiumphosphonate (TEDP) and an improved preparation of its 99mTc-TEDP complex. The results showed that the radiochemical purity of 99mTc-TEDP was found to be 95 ± 2% and that its stability was up to 6 h. Biodistribution study showed high and long uptake of 99mTc-TEDP in bone starting from 15 min (39 ± 4 ID/g) to 3 h (53 ± 2.4 ID/g) showing high affinity of 99mTc-TEDP complex to bones. This research could introduce a novel radiopharmaceutical that could be used in scanning body bones starting from 15 min between injection of 99mTc-TEDP and bone imaging, minimizing the burden on patients in terms of the total length of the examination and the dose of radiation absorbed and showing high specificity and efficacy in bone scintigraphy.

Zirconium molybdate gel was prepared by mixing (99)Mo, produced from (98)Mo(n,gamma) reaction and Zr solutions in nitrate media with excess H(2)O(2), and used as the base material for (99)Mo/(99m)Tc generator. The prepared generator showed a good performance. (99m)Tc eluted from the prepared generator passed the quality control tests with specifications meeting the requirements of European and US Pharmacopeias. The (99m)Tc eluate was used for labeling of cephalosporin analogue, ceftriaxone, which was then assessed for infection imaging in a mouse model. (99m)Tc-ceftriaxone was prepared at pH 9 with a radiochemical yield of 95+/-2% by adding (99m)Tc to 30 mg ceftriaxone in the presence of 50 microg SnCl(2).2H(2)O. Biodistribution studies in mice were carried out using experimentally induced infection in the left thigh using E. coli. Both thighs of the mice were dissected and counted to evaluate the ratio of bacterial infected thigh/contralateral thigh. (99m)Tc-ceftriaxone showed high uptake in the infectious lesion (T/NT =5.6+/-0.6 at 4h post injection). The abscess to normal muscle ratio indicated that (99m)Tc-ceftriaxone could be used for infection imaging. Besides, in vitro studies showed that (99m)Tc-ceftriaxone can differentiate between bacterial infection and sterile inflammation.