Development and bioevaluation of 99mTc(CO)3-labeled (1-azido-1-deoxy-ß-D-glucopyranoside) complex as a potential tumor-seeking agent.

The 1,2,3-triazole-containing (1-azido-1-deoxy-ß-D-glucopyranoside) complex was synthesized using click chemistry approach and evaluated its potential as a tumor-seeking agent. In the present study, (99m)Tc-tricarbonyl labeled (1-azido-1-deoxy-ß-D-glucopyranoside) radiotracer [(99m)Tc(CO)(3)-BM], (where BM stands for biomolecule, e.g., (1-azido-1-deoxy-ß-D- glucopyranoside)) was synthesized via click chemistry approach and then labeled with technetium-99m through isolink kit. Radio labeled drug was tested for radiochemical purity and in vitro stability by chromatographic techniques. Normal distribution and tumoral uptake were studied in Swiss Webster mice. Radiochemical purity results show 97.9 ±1.5% labeling and its in vitro stability were studied at room temperature up to 5h. The radio labeled drug exhibited 73.6±1.1% binding with blood proteins. Normal distribution of drug shows prominent uptake in brain while in case of tumor-bearing mice, the uptake was maximum in tumor tissue and negligible amount was shown in brain. The biodistribution was further compared with 2-fluoro-2-deoxy glucose ((18)F-FDG), which was used as a positive control. The data indicate that (99m)Tc-tricarbonyl labeled (1-azido-1-deoxy-ß-D- glucopyranoside) radiotracer might be a feasible candidate with reasonable potential for tumor diagnosis.

Biochemical analysis of the crude extract of Momordica charantia (L.).

Momordica charantia (L.) commonly referred as bitter gourd, karela and balsam pear. Its fruit is used for the treatment of diabetes and related conditions amongst the indigenous populations of Asia, South America, India and East Africa. The study was conducted to find out the biochemical aspects of crude extract of whole fruit of M. charantia including seeds which includes blood test (Hemoglobin, RBC, Total leukocyte count, platelets count, HbA1C (Glycocylated heamoglobin Type A1C)), Lipid profile test and electrolyte balance. Hemoglobin (7.1±0.14), platelets count (827 ×109±1.95), Cholesterol level (111±2), HDL (high density lipoproteins) (20±1.22) at 10mg shows marked increase in values as compared to control. While 25 mg dose shows insignificant result. Electrolyte balance are found significant at 10mg and 25mg except bicarbonates (Na(+¬)=143±1.87, K-=3.45±0.35, Cl(-) =108±1.48). Another important property of M. charantia is the elevation of platelet counts, heamoglobin and specifically high-density lipoproteins (HDL). It also controls cholesterol, triglycerides, HDL, LDL and VLDL at low dosage (10mg). Further studies can be conducted to find out which phytochemical components acts on specific biochemical activity.

Development of 99mTc-5-fluorouracil as a potential tumor diagnostic agent.

5-Fluorouracil is a well know drug for chemotherapy of various types of cancer. In the present study, we radiolabeled 5-fluorouracil with (99m)Tc for a diagnostic study of cancer. After successful labeling of the drug we performed an animal study to evaluate the potential of this radiopharmaceutical as a tumor diagnostic agent. The results showed 98.1 ± 1.2% labeling efficacy of 5-fluorouracil with (99m)Tc. The in vitro stability of the radiolabeled drug at room temperature at 4 hr of post-labeling was >96.5 ± 0.4%. The binding of the radiolabeled drug with plasma proteins was 66.6 ± 3%. Partition coefficient results showed that this drug is hydrophilic in nature. Biodistribution study in rabbit models displayed faint uptake in liver. Both kidney and bladder were prominent as excretory route of the labeled drug. Bioevaluation was performed in Swiss Webster mice having naturally developed tumor. Mice were dissected, uptake of drug in various organs was studied and results showed prominent uptake in liver and tumor. Tumor was further investigated by histopathological study.

Synthesis, characterization and bioevaluation of technetium-99m labeled N-(2-Hydroxybenzyl)-2-amino-2-deoxy-D-glucose as a tumor imaging agent.

N-(2-Hydroxybenzyl)-2-amino-2-deoxy-D-glucose (NHADG) was synthesized by conjugation of salicylaldehyde to glucosamine. The obtained compound was well characterized via different analytical techniques. Labeling of the synthesized compound with technetium-99m ((99m)Tc) in pertechnetate form ((99m)Tc O4-) was carried out via chelation reaction in the presence of stannous chloride dihydrate. Maximum radiochemical yield of (99m)Tc-NHADG complex (99%) was obtained by using 1 mg NHADG, 200 µg SnCl2.2H2O, at pH 9.5 and reaction time of 15 min. The radiochemical purity of the (99m)Tc-NHADG complex was measured by instant thin layer chromatography (ITLC) and paper chromatography (PC), without any notable decomposition at room temperature over a period of 4h. The biological evaluation results show that the (99m)Tc labeled NHADG conjugate is able to specifically target mammary carcinoma in mice models, thus highlighting its potential as an effective (99m)Tc labeled glucose-derived agent for tumor imaging.

In house development of (99m)Tc-Rhenium sulfide colloidal nanoparticles for sentinel lymph node detection.

In this study, rhenium sulfide colloidal nanoparticles were developed as radiopharmaceutical for sentinel lymph node detection. We directly used rhenium sulfide as a starting material for the preparation of colloidal nanoparticles. UV-visible spectrophotometry was used for characterization of in house developed colloidal particles. The size distribution of radioactive particles was studied by using membrane filtration method. The percentage of radiolabeled colloidal nanoparticles was determined by paper chromatography (PC). The study also includes in vitro stability, protein binding in human blood and bioevaluation in a rabbit model. The results indicate that 77.27 ± 3.26 % particles of size less than 20nm (suitable for lymphoscintigraphy) were radiolabeled. (99m)Tc labeled rhenium sulfide labeling efficacy with the radiometal is 98.5 ± 0.5%, which remains considerably stable beyond 5h at room temperature. Furthermore, it was observed that 70.2 ± 1.3% radiolabeled colloid complex showed binding with the blood protein. Bioevaluation results show the remarkable achievement of our radiopharmaceutical. The in house prepared (99m)Tc labeled rhenium sulfide colloidal nanoparticles reached the sentinel node within 15 min of post injection. These results indicate that (99m)Tc labeled rhenium sulfide colloid nanoparticles kit produced by a novel procedure seems of significant potential as a feasible candidate for further development to be used in clinical practice.

Preparation and biodistribution in mice of a new radiopharmaceutical-technetium-99m labeled methotrexate, as a tumor diagnostic agent.

Our aim was to develop the procedure for radiolabeling of an anticancer drug e.g., methotrexate with (99m)Tc for tumors diagnosis. The study included the radiolabeling of methotrexate, in vitro stability of radiolabeled drug, in vitro binding of radiolabeled drug with plasma protein, partition coefficient and biodistribution of radiolabeled drug in mice. Results showed 98.2±0.5% radiolabeling of methotrexate with technetium-99m ((99m)Tc). In vitro stability was studied for 5h and 79.3±5% of the drug was bound with plasma proteins. Partition coefficient of the labeled drug showed that it was highly hydrophilic. Biodistribution study in tumor bearing mice exhibited high uptake in tumor cells which were further investigated by histopathological studies. In conclusion, our study indicates that technetium-99m labeled methotrexate is a potentially strong tumor diagnostic agent with low uptake in normal tissues.

Preperation of (99m)Tc labeled 5-fluorouracil as a potential diagnostic agent in advanced breast cancer: first clinical trial.

The chemotherapeutic drug 5-fluorouracil (5FU) is used for treatment of various types of cancers. The present study was conducted to evaluate the potential of this drug as a diagnostic radiopharmaceutical in advanced breast cancer. We have labeled 5FU by using the stannous chloride reduction method with 555MBq of technetium-99m ((99m)Tc). The (99m)Tc-5FU was injected intravenously in 4 patients having advanced breast cancer. Dynamic and static images were taken at various time intervals till 2h. Whole body images were used to calculate the percentage of the injected dose, in each organ. Target to non target ratio was calculated to find out the optimum time for imaging. In conclusion, our study showed that (99m)Tc-5FU was a promising agent for diagnosing advanced breast cancer with optimum visualization at 1h.

Synthesis, characterization and biodistribution of novel amine thiophene 99mTc labeled complex.

(99m)Tc-labeled amine thiophene ligand might be a potential candidate for brain imaging. The purpose was to investigate the uptake of a radiolabeled drug in the brain. In this study, a tetradentate amine-thiophene-dione ligand was synthesized by the reaction of thiophene-2-carboxaldehyde with ethane-1,2-diamine and reducing with NaBH(4). The ligand system was characterized by elemental analysis, FTIR and 1H NMR. Radiolabeling of the complex with (99m)Tc was performed by reducing with stannous ions. The radiochemical purity of the radiolabeled drug was determined by paper chromatography (PC) and instant thin layer chromatography (ITLC). Bioevaluation of the (99m)Tc complex was studied in rabbits. The yield of the final product was 4.42 g (60%) and the characterization data confirmed the synthesis of the final product. The efficacy of radiolabeling was >98%. A significant uptake was observed in the brain which retained significantly upto 4h. The data indicate that the proposed system may be suitable for brain imaging in future clinical applications.