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2,3,7,8,12,13,17,18-Octaethyl-21H,23H-porphine (OEP) was successfully radiolabeled with technetium-99m by direct technique using two different reducing agents: stannous chloride and sodium borohydride. High radiochemical yield (97%) and in vitro stability for up to 8 h were obtained using sodium borohydride. Paper chromatography (PC), paper electrophoresis, and high-performance liquid chromatography (HPLC) were used to evaluate the radiochemical yield and identify the purity of the final product. Biodistribution studies of the 99mTc-OEP complex (prepared using sodium borohydride) in tumor-bearing mice showed high target/nontarget (T, right thigh/NT, left thigh) ratio of 4.40 ± 0.12 at 60 min post injection, suggesting that this complex can be used as a solid tumor imaging agent.

The objective of this work was to develop a potential selective radiotracer for the non-invasive assessment of heart imaging. [125I]iododobutamine was obtained via direct electrophilic substitution reaction with a high labeling yield of 96.79 ± 0.86%. The in vivo biodistribution of iodinated dobutamine showed high heart uptake of 31.49 ± 1.3%ID/g at 2 min after injection with low lungs and liver consumption which alleviate rapid myocardial imaging with significant minimum radiation hazards risk to the patients. Receptor blocking study showed reduction of heart uptake to 0.9 ± 0.01% which confirm the selectivity and specificity of [125I]iododobutamine for beta-adrenoceptors.

Aspirin, one of nonsteroidal anti-inflammatory analgesic drugs, was labeled with 125I with a labeling yield of 85.5% under the following conditions: pH 9, 100 mg of the substrate, 50 µg of Chloramine-T, 5–15 min, room temperature. The radiochemical yield of 125I-aspirin was determined by paper chromatography and electrophoresis, and the radiochemical purity was determined by HPLC.125I-aspirin was stable for at least 3 h. Biodistribution of 125I-aspirin in normal and tumor-bearing mice was studied. The uptake of 125I-aspirin in tumor sites makes it promising as a new radiopharmaceutical for tumor imaging.

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.

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

Haloperidol (HP) is a dopamine blocking agent. HP was radiolabeled with 125I using direct electrophilic substitution. Different HP formulations such as intravenous solution (VS), intranasal solution (NS) and intranasal microemulsion (NME) have been prepared. Optimum labeling yield of 125I-HP was obtained 93.42 ± 1.53%. Isopropylmyristate oil (10%), Tween 80 (30%), propylene glycol (15%) and aqueous phase (45%) were used for NME preparation. Using Swiss Albino mice, the % brain uptake were 1.4 ± 0.2, 4.3 ± 0.2 and 5.7 ± 0.4% for VS, NS and NME, respectively. 125I-HP in NME formula showed superiority as drug delivery system for brain imaging.

3-Benzyl-2-((3-methoxybenzyl)thio)benzo[g]quinazolin-4(3H)-one was previously synthesized and proved by physicochemical analyses (HRMS, 1H and 13C NMR). The target compound was examined for its radioactivity and the results showed that benzo[g]quinazoline was successfully labeled with radioactive iodine using NBS via an electrophilic substitution reaction. The reaction parameters that affected the labeling yield such as concentration, pH and time were studied to optimize the labeling conditions. The radiochemical yield was 91.2 ± 1.22% and the in vitro studies showed that the target compound was stable for up to 24 h. The thyroid was among the other organs in which the uptake of 125I-benzoquinazoline has increased significantly over the time up to 4.1%. The tumor uptake was 6.95%. Radiochemical and metabolic stability of the benzoquinazoline in vivo/in vitro and biodistribution studies provide some insights about the requirements for developing more potent radiopharmaceutical for targeting the tumor cells. Keywords: Benzo[g]quinazoline, Radioiodination, Biodistribution, Tumor cell, NBS

4-{(4-Methylphenyl)glycyl}-3,4-dihydroquinoxalin-2(1H)-one (QIN) was prepared from 4-(2-chloroacetyl)- 3,4-dihydroquinoxalin-1(1H)-one). 125I-QIN was prepared by electrophilic substitution using Chloramine- T as an oxidizing agent. The highest labeling yield, 94%, was obtained under the following conditions: pH 7, 15 min, 100 μg of QIN, 50 μg of Chloramine-T, and carrier-free Na125I. The labeled compound was stable for up to 12 h post labeling. A biodistribution study of 125I-QIN in mice showed that its brain uptake was about 5.1% at 30 min post injection and remained on this level up to 1 h. As compared to commercially used radiopharmaceuticals for brain imaging, 125I-QIN is more stable and shows higher brain uptake.

A newly synthesized s-triazine derivative 1,1',1″-(((1,3,5-triazine-2,4,6-triyl) tris (azanediyl)) tris (benzene-4,1-diyl))tris (ethan-1-one), (1), was synthesized as a part of an ongoing research for development of novel s-triazine-based radiopharmaceuticals. In-vitro cell viability assay against different human cancer cell lines showed very promising inhibitory activity of the synthesized compound. This finding encouraged the radioiodination of 1 to study the degree of its localization in tumor site for evaluating the possibility of its use as a tumor imaging agent. The biodistribution study showed good localization of the radioiodinated derivative 2 at tumor site following i.v. administration in solid tumor-bearing mice. Finally, in a trial to understand the mechanism of the anticancer effect exerted by 1, a target prediction study and a docking study were performed. The results of the first study showed that focal adhesion kinase is a possible target for compound 1 and the docking study confirmed successful binding of both compound 1 and its radioiodinated derivative 2 to the binding site of focal adhesion kinase. As a conclusion, the results of this study suggest that, compound 2 could be used as a potential agent for tumor imaging after preclinical trials.

1,3,5-Triazine-based compounds form a privileged class of compounds in the medicinal chemistry field as they are versatile synthetic scaffolds possessing wide spectra of biological effects including potential anticancer activity. 1,3,5-Triazine compounds explored for anticancer activities have been reported to act by various mechanisms on several molecular targets in human cells such as methyltransferase (DNMT), heat shock protein 90 (Hsp90) and phosphoinositide 3-kinase (PI3K). This review focuses on the synthetic strategies for current developments of 1,3,5-triazine-based anticancer agents and discuses the docking studies that confirm their unique binding modes in the targeted receptors active sites. This article also aims to highlight the future directions for the easy access to these frameworks of more potent and specific anticancer activity.

Background: Recently, the direct intratumoral (i.t.) injection of anticancer agents has been investigated. A newly synthesized Antineoplaston A10 analog 3-(4-methoxybenzoylamino)-2,6-piperidinedione (MPD) showed an antitumor activity in human breast cancer cell line. Unfortunately, MPD suffered from poor water solubility. Materials and Methods:Pseudoternary phase diagram of oil (isopropyl myristate), surfactant (Tween 80), cosurfactant (ethanol), and water was plotted. MPD microemulsion (MPDME) was developed and characterized for particle size (PS), polydispersity index (PDI), zeta potential (ZP), and morphology (transmission electron microscopy). MPDME and MPD solution (MPDS) were radiolabeled with technetium 99m (99mTc) using stannous chloride dihydrate (SnCl2.2H2O). Molecular docking of MPD and 99mTc-MPD was performed to study the interaction with DNA. Results:The impacts of intravenous (i.v.) and i.t. injections of 99mTc-MPDME and 99mTc-MPDS on biodistribution were studied. The developed MPDM...

A10, (3-phenylacetylamino-2,6-piperidinedione), is a natural peptide with broad antineoplastic activity. Recently, in vitro antitumor effect of a new A10 analog [3-(4-methoxybenzoylamino)-2,6-piperidinedione] (MPD) has been verified. However, poor aqueous solubility represents an obstacle towards intravenous formulation of MPD and impedes successful in vivo antitumor activity. To surmount such limitation, MPD microemulsion (MPDME) was developed. A 3122 full factorial design using Design-Expert® software was adopted to study the influence of different parameters and select the optimum formulation (MPDME1). Transmission electron microscopy (TEM) displayed spherical droplets of MPDME1. The cytotoxicity of MPDME1 in Michigan Cancer Foundation 7 (MCF-7) breast cancer cell line exceeded that of MPD solution (MPDS) and tamoxifen. Compatibility with injectable diluents, in vitro hemolytic studies and in vivo histopathological examination confirmed the safety of parenteral application of MPDME1. Molecular docking results showed almost same binding affinity of A10, MPD and 125I-MPD with histone deacetylase 8 (HDAC8) receptor. Accordingly, radioiodination of MPDME1 and MPDS was done via direct electrophilic substitution reaction. Biodistribution of 125I-MPDME1 and 125I-MPDS in normal and tumor (ascites and solid) bearing mice showed high accumulation of 125I-MPDME1 in tumor tissues. Overall, the results proved that MPDME represents promising parenteral delivery system capable of improving antineoplastic activity of MPD.

The present study was oriented to synthesis radioiodinated celiprolol (Cel) for a potential cardiac imaging. Celiprolol has been labeled using 125I with chloramine-T (Ch-T) as an oxidizing agent. The key effective factors such as amount of oxidizing agent, amount of substrate, pH, reaction temperature and reaction time, have been systematically studied to optimize the iodination. The biological distribution indicates the suitability of radioiodinated Cel as a novel tracer to image heart.

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.

Uridine, a pyrimidine nucleoside essential for the synthesis of RNA and biomembranes, was radiolabeled with 99mTc to obtain a potential tumor imaging agent. The maximal radiochemical yield of about 96.5%, as determined by paper chromatography and instant thin-layer chromatography, was reached under the following optimum conditions: 1 mg of uridine, 20 μg of SnCl2·2H2O as reducing agent, 20 mg of mannitol as a stabilizer, and pH 8. 99mTc-uridine is stable in vitro at room temperature for up to 6 h post labeling. The biodistrbution study in tumor-bearing mice shows high target-to-nontarget ratio. These results match with the high docking score of the complex on uridine phosphorylase enzyme. 99mTc-uridine shows promise as a tumor imaging agent.

The design and synthesis of ethyl 4-(6-amino-7-cyano-2,3-dihydro-1H-pyrrolizine-5-carboxamido)-benzoate (KH16) were discussed, and its structure was determined. The anti-inflammatory activity of a new compound was evaluated using in vitro cyclooxygenase (COX) inhibitory assay. KH16 exhibits higher selectivity to COX-2 than to COX-1 with the selectivity index of 3.46. KH16 was labeled with 99mTc with the maximum radiochemical yield of 99mTc-KH16 of 90.5 ± 1.5%. Biodistribution of 99mTc-KH16 in normal, infected, and inflamed mice was studied. The uptake in inflamed muscle was higher than that in normal muscle throughout the examined time interval. This work is a step ahead in the direction of using pyrrolizine derivatives for site-specific delivery to the inflamed tissue.

Hexoprenaline and dapoxetine (two lung selective pharmaceutical compounds) were radiolabeled to produce lung imaging radiopharmaceuticals using 99mTc and 131I, respectively. Different factors affecting labeling process were examined and optimum radiochemical purities of 91.3 ± 0.294 and 96.5 ± 0.342% were obtained, respectively. In silico molecular modeling studies for 99mTc-hexoprenaline and 131I-dapoxetine were done. Molecular modeling studies of the radiolabeled compounds examined the effect of radiolabeling on structure activity relationship for hexoprenaline and dapoxetine. Biodistribution studies in Swiss albino mice showed poor lung uptake of 99mTc-hexoprenaline and high uptake for 131I-dapoxetine (15.26 ± 0.11 and 55.82 ± 0.201%ID/g, respectively) matching the molecular modeling expectations. Consequently, 131I-dapoxetine could be a hopeful radiopharmaceutical for lung scintigraphic imaging and further studies to radiolabel hexoprenaline with 131I are recommended.

A novel zoledronic acid (ZL) derivative, 3-(2-ethyl-4-methyi-1H-imidazole-1-yl)-1-hydroxy-1-phosphonopropyl phosphonic acid (EMIHPBP), was synthesized, characterized and successfully radiolabeled with 99mTc. The in-vivo biodistribution of 99mTc-EMIHPBP was investigated and compared with the previously reported zoledronate derivatives aiming to formulate a novel zoledronate derivative with a high potential uptake to bone as a promising antiosteoporotic candidate. In order to further evaluate the bone uptake efficiency, the pharmacokinetics of 99mTc-EMIHPBP was investigated, and showed that maximum concentration in bone (Cmax) was 31.60±0.15%ID/gram after 60min (tmax). Cumulative residence of 99mTc-EMIHPBP in the bone [AUC (0-∞) (%ID.min /gram bone)] was 3685.23, mean residence time (MRT) was 384.354min and the calculated bone bioavailability was 15.831%. Finally, the time needed for half of the 99mTc-EMIHPBP formulation to be eliminated from bone (t1/2) was 263.914min. Excellent bone uptake can be obtained 1h post injection with high bone\blood ratio of 23.76 detected with gamma counter. The biodistribution and kinetic studies could recommend EMIHPBP as a promising antiosteoporotic candidate with high selectivity to the skeletal system and rapid clearance from soft tissues.

To develop a radiopharmaceutical localizing in tumor hypoxic tissues, secnidazole (SECN) was labeled with 125I. The labeled product was prepared with the radiochemical yield higher than 96% when performing the reaction at 45°C for 30 min. The electrophilic radioiodination of SECN was done using different oxidizing agents. Iodogen appeared to be more effective than chloramine-T (CAT) and N-bromosuccinimide (NBS). 125I-SECN was tested in vivo with a tumor model prepared by the intramuscular injection of Ehrlich cell line into the thigh muscle of mice. 125I-SECN showed high accumulation in tumor hypoxic tissue (3.6% of injected dose per gram of organ at 2 h post injection). The target/nontarget (T/NT) ratio was high (T/NT = 6 at 24 h post injection). Thus, radioiodinated SECN shows promise as a selective imaging agent for diagnosis of tumor hypoxia.

3-Amino-2-quinoxalinecarbonitrile 1,4-dioxide (QN) was labeled with 125I, and the biological distribution of the product was studied. 125I-QN was prepared by direct electrophilic substitution reaction using N-bromosuccinimide (NBS) as an oxidizing agent. The radiochemical yield of 92% was reached under the following optimum conditions: pH 7, 15 min, 100 μg of QN, and 75 μg of NBS. The labeled QN was stable for up to 12 h post labeling. Biodistribution study of 125I-QN in tumor-bearing mice reflected that it accumulated in tissues with high proliferation rate with preferential accumulation in tumor sites. 125I-QN was incorporated rapidly in the tumor site (T/NT = 4 at 2 h post injection), and then its content slowly decreased, whereas in the other tissues it decreased rapidly. The results obtained encourage the use of 123I-QN as a tumor imaging agent.

Timonacic acid (TCA) was successfully labeled with 99mTc. The influence exerted on the reaction by the substrate and reducing agent concentrations, pH of the reaction mixture, and reaction time was examined, and in vitro stability of 99mTc-TCA was evaluated. The maximum labeling yield was 98.5 ± 0.6%. The complex was stable throughout the working period (6 h). A study of in-vivo biodistribution in mice showed that the maximum uptake of 99mTc-TCA in the liver was 22.3 ± 0.3% of the injected activity per gram of the tissue or organ (% ID/g) at 30 min post injection. The clearance from the mice appeared to proceed via the circulation mainly through the kidneys and urine (approximately 56% of the injected dose at 1 h after injection). The liver uptake of 99mTc-TCA is higher than that of 99mTc-UDCA (ursodeoxycholic acid); therefore, 99mTc-TCA shows more promise for liver SPECT.

Procainamide (4-amino-N-[2-(diethylamino) ethyl] benzamide) is a sodium channel blocker, which acts as an effective antiarrhythmic agent used in the treatment of a variety of atrial and ventricular arrhythmias. The aim of this study was to prepare 99mTc-procainamide complex, apply different chromatographic techniques for the assay of radiolabeling yield and study its biodistribution as a novel radiopharmaceutical for heart imaging. 99mTc-procainamide was obtained with a maximum labeling yield of 95.76±0.20% via direct labeling method under optimum conditions of 200 μg of procainamide, 300 μL of buffer (carbonate) at pH 11, 30 μg SnCl2·2H2O at room temperature (25°C) for 15 min. In terms of in vitro stability, the complex was stable for 3 h. Chromatographic evaluation using paper chromatography, thin layer chromatography, gel chromatography, and high performance liquid chromatography showed reliable results for measuring the radiochemical yield. Biodistribution study of 99mTc-procainamide showed ratios of heart/lung and heart/liver (6.38±1.50, 2.06±0.31, respectively at 30 min post injection) which was comparable to that of 99mTc-sestamibi (7.4±2.00, 0.97±0.10, respectively at 60 min, P

Radiolabeling of histidine (Hist), an essential amino acid, with 99m Tc was performed. The radiochemical yield higher than 95% was achieved with stannous chloride as a reducing agent. Factors affecting the radiochemical yield (histidine amount, stannous chloride amount, reaction time, pH of the reaction mixture) were studied in detail, and the reaction conditions were optimized. In vitro stability of the radiolabeled complex was checked, and it was found to be stable for up to 6 h. 99m Tc-Hist was injected intravenously into normal and tumor-bearing mice. Biodistribution studies revealed that the 99m Tc-Hist uptake in tumor sites was 10 and 16% ID/g in ascites and 7 and 9.2% ID/g in thigh solid tumor at 60 and 120 min post injection, respectively. The amount of 99m Tc-Hist in ascites and solid tumor increased with time and then decreased slowly. Thus, 99m Tc-Hist can be used as a potential agent for imaging tumor sites.

Meclofenoxate is a drug used to cause a broad improvement in brain function and mental performance. Meclofenoxate was successfully labeled with 125I via direct electrophilic substitution reaction at room temperature. Percent radiochemical yield was evaluated by paper electrophoresis and HPLC. The reaction parameters affecting the preparation process were studied in details. 125I-meclofenoxate gave maximum percent radiochemical yield of about 95 ± 1.0% with specific activity 1.9 μCi/μg meclofenoxate and its stability was up to 4 h. Biodistribution studies showed that maximum uptake of 125I-meclofenoxate in the brain of mice was 4.27 ± 0.3% injected dose (ID)/g tissue organ at 15 min post-injection. This uptake of 125I-meclofenoxate was found to be enough to image brain as it still 4.3% ID/g at 30 min post injection.

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.

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.

Rabeprazole, antiulcer drug, was labeled with 99m Tc to obtain an agent for ulcer imaging. The radiochemical yield of 99m Tc-rabeprazole reaches approximately 98.5 ± 0.4%.The optimum conditions are as follows: pH 9, 50 μg of SnCl2·2H2O, 30 min, and 3 mg of the substrate.99m Tc-rabeprazole was stable for 6 h. Intravenous biodistribution studies of 99m Tc-rabeprazole revealed high concentration in the stomach ulcer, reaching about 33.4% of the total injected dose at 30 min post injection. This concentration of 99m Tc-rabeprazole in stomach ulcer makes this agent promising for stomach ulcer 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.

Objectives: This study aimed at exploring the possibility of radiolabeling 5-Azacytidine with technetium-99m (99mTc) as a surrogate for Rhenium- 186/188 in order to explore the possibility of using the radiolabeled complex as a targeted radiotherapeutic agent. Methods: Radiolabeling of 5-Azacytidine with 99mTc via complexation reaction using stannous chloride dihydrate as a reducing agent. The biodistribution of the formed complex was then studied in tumour bearing mice. Results: Successful radiolabeling of 5-Azacytidine with 99mTc was achieved with radiolabeling yield 84.94%. The formed complex showed in vitro stability up to 60 min post labelling. The biodistribution study of the complex showed a Target /Non-target ratio of 2.27 at 2h post injection suggesting good localization of the complex. Conclusion: The radiolabeling of 5-Aza was successfully achieved with 99mTc. The biodistribution study in tumour bearing mice showed good localization of the radiolabeled complex at the tumour site, however further studies are needed for achieving better targeting of the complex.

An adopted method for the preparation of high radiochemical purity [ 125 I] iodoepinephrine was developed in order to characterize the binding properties of adrenergic receptors. Direct radioiodination of epinephrine was carried out using chloramine-T as oxidizing agent. The reaction proceeds well within 15 min at ambient room temperature up to 25+1oC and afforded a radiochemical yield up to 94%. Different chromatographic techniques (electrophoresis and pap er chromatography) were used to evaluate the radiochemical yield and purity of the labeled product. Biodistribution studies were carried out in normal Albino Swiss mice and the results showed rapid and high cardiac uptake of 125 I-epinephrine. The result in dicates the possibility of using radioiodinated epinephrine as myocardial imaging agent.

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 1 mg of the compound, 50 µg CAT oxidizing agent, 30 min as reaction time at pH with a yield about 95%. The 125I-coumarin derivative was stable for about 48 h. 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 1 h and 4 h post-injection. This uptake encourages the use of 123I-coumarin derivative in imaging of tumor sites., Highlights • Labeling of coumarin derivative with iodine-125. • The appropriate conditions for labeling of coumarin derivative (95% yield). • 125I-coumarin derivative was found to be highly localized in tumor.

Ritodrine (a beta-2 adrenergic receptor agonist) was successfully labeled with 125I via direct electrophilic substitution reaction at ambient temperature. 125I-ritodrine was obtained with a maximum labeling yield of 97 ± 0.163 % and in vitro stability up to 24 h. Biodistribution studies showed that maximum in vivo uptake of 125I-ritodrine in lungs was 20.4 ± 0.22 % injected activity/g tissue at 1 h post-injection, whereas the clearance from mice appeared to proceed mainly via the renal pathway. 125I-ritodrine is not a blood product and so it is more safe than the currently available 99mTc-MAA, and its lung uptake is higher than that of the recently discovered 99mTc(CO)5I and 99mTc-DHPM. As a conclusion, radioiodinated ritodrine could be used as a novel radiopharmaceutical for lung perfusion scan safer than the currently available 99mTc-MAA and more potential than the recently discovered 99mTc(CO)5I and 99mTc-DHPM.

Bambuterol·HCl was successfully labeled with 125I via direct electrophilic substitution at ambient temperature. The effect of reaction parameters such as Bambuterol amount, CAT amount, pH of the reaction mixture, reaction temperature, and reaction time and the in vitro stability of 125I-Bambuterol·HCl were studied. The maximum yield of 125I-Bambuterol·HCl was 92.5 ± 1.9%. The yield was determined by paper electrophoresis. In vitro stability study showed that it is preferred to use the freshly prepared agent. Biodistribution studies showed high uptake of 125I-Bambuterol·HCl in liver and lungs (16 ± 0.15 and 4.3 ± 0.08% injected dose/g tissue, respectively, at 5 min post injection). The uptake in liver and lung remained high up to 1 h, as β2-receptors are located mainly at the liver and lungs (bronchial smooth muscles). The clearance of 125I-Bambuterol·HCl from mice appeared to be mainly via the renal pathway. Radioiodinated Bambuterol·HCl shows promise as novel selective β2-adrenoceptor imaging agent.

A procedure was developed for preparing high radiochemical purity 99m Tc-Losartan in a yield of about 90%. The optimal reaction conditions are as follows: 100 μg of Losartan, 50 μg of SnCl2·2H2O, 150 μL of phosphate buffer (pH 7), room temperature (25 ± 1°C), reaction time 5 min. Under these conditions, the radiochemical yield up of 99m Tc-Losartan reaches 98%. The radiochemical yield and purity of the labeled product were determined by electrophoresis and paper chromatography. Biodistribution studies were carried out in normal Albino Swiss mice at different time intervals after administration of 99m Tc-Losartan. The labeled compound cleared from the systematic circulation within 3 h after administration, and the majority of organs showed significant decrease in the uptake of 99m Tc-Losartan. The heart uptake of 99m Tc-Losartan was sufficiently high for using this agent as myocardial imaging agent.

Pantoprazole, antiulcer drug, was labeled with 99m Tc to obtain an agent for ulcer imaging. The radiochemical yield of 99m Tc-Pantoprazole reaches approximately 96.5%. The optimum conditions are as follows: pH 10, 75 μg of tin chloride, 30 min, and 2 mg of the substrate. 99m Tc-Pantoprazole was stable for 3 h. Intravenous biodistribution studies of 99m Tc-Pantoprazole revealed high concentration in the stomach ulcer, reaching about 27.2% of the total injected dose at 30 min post injection. This concentration of 99m Tc-Pantoprazole in stomach ulcer makes this agent promising for stomach ulcer imaging.

Aripiprazole was successfully labeled with radioactive iodine using chloramine-T via an electrophilic substitution reaction. The influence exerted on the labeling yield by reaction parameters such as concentration, pH, and time was studied to optimize the labeling conditions. The radiochemical yield was 96 ± 3%. The radioiodinated compound was separated by HPLC. In vitro studies showed that the compound was stable for up to 24 h. The brain uptake was 5.53%, which was higher than that for the commercially available Ceretec kit. The clearance from the rats occurs via the hepatobiliary and renal pathways. Predosing the rats with cold aripiprazole reduced the brain uptake to 1.9 ± 0.1% and further confirmed that the uptake of this radioiodinated compound was specific for the brain. A mechanism of the formation of electropositive iodine is discussed, and possible oxidizing species of Chloramine-T in both acidic and alkaline media are ascertained.

The aim of this work was to develop a novel 99mTc-labelled derivative based on triphenylethylene for breast cancer imaging. 99mTc-Clomiphene was obtained with a radiochemical yield of 94.4% by adding 99mTc to 1.5 mg Clomiphene citrate in the presence of 10 μg SnCl 2 at pH 7. The optimization of the labeling yield of Clomiphene citrate, with 99mTc, is described. The reaction parameters that affect the labeling yield were studied to optimize the labeling conditions. Radiochemical purity of the final product has been verified by means of paper chromatography and paper electrophoresis. Ehrlich Ascites Carcinoma (EAC) as a model of breast cancer cells was injected intraperitoneally (IP) to produce ascites and intramuscularly (IM) to produce solid tumor. Biodistribution study was carried out by the injecting solution of 99mTc-Clomiphene in normal and tumor bearing mice. The uptake in ascites was over 12.5 % injected dose per gram tissue body weight, at 1hr after injection and above 12% in solid tumor. The T/NT value for 99mTc-Clomiphene complex was found to be which was higher than that of the commercially available 99mTc-MIBI. This data revealed the localization of tracer in tumor tissue with high percent sufficient to use 99mTc-Clomiphene as a promising tool for the diagnosis of breast cancer.

NBNPQD (2-benzyl-1-oxo-1,2-dihydropyrido[4,3-b]quinoxaline 5,10-dioxide) is a new synthesized quinoxaline derivative. It could be labeled with auger emitter 125I successfully with yield about 90 %. The labeled product was evaluated by electrophoresis and thin layer chromatography. Factors affected labeling yield were studied. 125I-NBNPQD was stable up to 48 h post labeling. Biodistribution study of 125I-NBPQD in normal and tumor bearing mice was also conducted. The biodistribution data revealed that 125I-NBNPQD diffused rapidly to tumor sites in both ascites and solid tumor bearing mice. 125I-NBNPQD was declined rapidly from most of organs but slowly from tumor sites. In vitro radiotoxicity of 125I-NBNPQD increased with the increase of its radioactivity. This study encourages the possible use of 125I-NBNPQD in tumor imaging and treatment. It also encourages further studies on the chemotherapeutic activity of NBNPQD hoping to get a new potent antitumor agent.

Quinoxaline 1,4-dioxide derivative, 2-{[benzyl(cyanomethyl)amino]methyl}-3-(ethoxycarbonyl) quinoxaline 1,4-dioxide (Q3D), was synthesized and labeled with radioiodine via direct electrophilic substitution giving labeling yield above 90%. The product was examined by paper electrophoresis. 125I-Q3D was prepared using Chloramine T as oxidizing agent. 125I-Q3D was stable for up to 72 h post labeling, in contrast to 99mTc-AQCD which is stable only for a short time. Biodistribution study of 125I-Q3D in ascites tumor bearing mice revealed large uptake of the labeled compound in tumor sites. In addition, in vitro incubation of the labeled compound with Ehrlich cells indicated incorporation of these compounds in DNA of tumor cells. This uptake of 125I-Q3D in DNA of tumor cells may be helpful in tumor diagnosis and therapy.

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.

Tannic acid is a polyphenolic compound that could be labeled with technetium-99m. To produce about 90% yield of 99mTc-tannic acid in acidic media (pH), the conditions required were 150 g tin chloride, 30 min reaction time, and 200 g of the substrate. 99mTc-tannic was stable for 6 h. Oral biodistribution of 99mTc-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 99mTc-tannic in stomach ulcer may be sufficient to radio-image the presence of ulcer in the stomach.

The aim of this study was to develop a potential selective radiopharmaceutical for the non-invasive assessment of cardiac β1-adrenoceptors in vivo. Nebivolol is a cardioselective β1-adrenergic receptor antagonist that was successfully labeled with NCA 125I via direct electrophilic substitution at ambient temperature. The reaction parameters studied were nebivolol concentration, pH of the reaction mixture and kinds of oxidizing agents. The radiolabeled compound maintained its stability throughout working period of 24 h. In vivo uptake of 125I-nebivolol in the heart was 8.51 ± 0.01% ID/organ at 0.5 h post-injection, whereas the clearance pathways from the rats appear to proceed via the hepatobiliary and renal clearance. Administration of cold nebivolol reduced the heart uptake to 2.1 ± 0.13% and further confirms the high specificity and selectivity of this radiotracer for the myocardial β1-adrenoceptors.

Radiolabeling of oxybutynin, a muscarinic acetylcholine (mACh) receptor antagonist agent with 99mTc is of considerable interest for imaging of urinary bladder. This study is aimed to optimize radiolabeling yield of oxybutynin with 99mTc using SnCl2·2H2O as a reducing agent with respect to factors that affect the reaction conditions such as oxybutynin amount, stannous chloride amount, reaction time and pH of the reaction mixture. In vitro stability of the radiolabeled complex was checked and it was found to be stable for up to 8 h. 99mTc-oxybutynin was injected via subcutaneous and intravenous administration routes into normal Sprague–Dawley rats. Biodistribution studies have revealed that 99mTc-oxybutynin exhibits high affinity and specificity for the muscarinic M3 subtype located on the smooth muscle of urinary bladder relative to the M1 and M2 subtypes of the G protein coupled receptor (GPCR) superfamily. In vivo uptake of subcutaneous 99mTc-oxybutynin in urinary bladder was 19.6 ± 0.42% ID at 0.5 h, whereas in intravenous administration route the accumulation in the urinary bladder was found to be 9.4 ± 0.31% ID at 0.5 h post injection. Administration of cold oxybutynin effectively blocked urinary bladder uptake and further confirms the high specificity of this complex for the M3 receptor.

The optimization of the radiolabeling yield of ciprofloxacin analogous, norfloxacin, with technetium-99m (99mTc) was described. Dependence of the labeling yield of 99mTc–norfloxacin complex on the concentration of norfloxacin, SnCl2·2H2O content, pH of the reaction mixture and reaction time was studied. Norfloxacin was labeled with 99mTc at pH 3 with a labeling yield of 95.4% by using 5 mg norfloxacin, 50 μg SnCl2·2H2O and 30 min reaction time. The formed 99mTc–norfloxacin complex was stable for a time up to 3 h. Biological distribution of 99mTc–norfloxacin complex was investigated in experimentally induced inflammation rats using Staphylococcus aureus (bacterial infection model) and heat killed Staphylococcus aureus and turpentine oil (sterile inflammation model). In case of bacterial infection, the T/NT value for 99mTc–norfloxacin complex was found to be 6.9 ± 0.4 which was higher than that of the commercially available 99mTc–ciprofloxacin under the same experimental condition.