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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.

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.

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.

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.

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.

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.

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.

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.

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.

125I-Metoprolol was prepared by electrophilic substitution reaction in the presence of Chloramine-T (CAT) as an oxidizing agent. The reaction conditions were optimized. The radiochemical yield of 125I-metoprolol exceeding 90% was attained in 10 min at ambient temperature (25 ± 1°C). The radiochemical yield and purity of the labeled product were evaluated by electrophoresis, thin-layer chromatography (TLC), and high-performance liquid chromatography (HPLC). Biodistribution studies of 125I-iodometoprolol were carried out in normal Albino Swiss mice. The results indicate the possibility of using [125I]-iodometoprolol for myocardial imaging.