Atomic Energy Council-institute of Nuclear Energy Research

Institute of Nuclear Energy Research, Atomic Energy Council, Executive Yuan, R.o.c

Institute of Nuclear Energy Research, Atomic Energy Council, Executive Yuan

Cheng-Fang Hsu

Yu Lung Chang

Show-Wen Liu

Cheng-Hsien Lin

Tsyh-Lang Lin

Chih-Yuan Lin

Tsung-Hsien Chiang

Kuei-Lin Lu

Yueh-Feng Deng

Ching-Yun Lee

Wuu-Jyh Lin

Da-Ming Wang

Ching-Yun Li

Sheng-Lun Lin

Ming-Che Tsai

Mei-Hui Wang

Jenn-Tzong Chen

Lie-Hang Shen

Wen-Ching Wu

Chyng-Yann Shiue

Shu-Hung Lin

Shiou-Shiow Farn

Jen-Tsung Wang

Yu-Lung Wu

I-Chung Tang

Kwei-Luen Hsu

Te-Sheng Liang

Chang-Mau Sheng

Ching-Jun Liou

Haw-Jan Chen

Wei-Ti Kuo

Hung-Wen Yu

Jia-Dong Tsai

Sheng-Po Huang

The present invention provides a method for preparing S-Bz-MAG3 as a precursor of contrast media. Thioglycolic acid and benzoyl chloride are taken for the thiol protection reaction. Next, N,N'-dicyclohexylcarbodiimide and N-hydroxysuccinimide are converted to corresponding ester compounds. The corresponding ester compounds then react with triglycine by amide bonding reaction. The product of the reaction is recrystallized using acetone, filtered, and finally flushed using flushing agent to give the final product. This is a bifunctional chelator and can be bridged with 99mTc and 186/188Re effectively and applied to nuclear medicine imaging and tumor radiotherapy. By taking advantage of fewer synthesis steps and ease of operations, complicated separation and purification reactions can be reduced and thus achieving highly productivity of S-Bz-MAG3.

Method for preparing S-Bz-MAG3 as a precursor of contrast media

A [F-18]FEONM precursor is synthesized. 2-bromoethanol is added to further connect an atom of oxygen at an N terminal of the precursor. Four atoms of carbon can be further connected. Thus, better fat-solubility is obtained along with the increase in carbon. Positioning in brain imaging becomes better.

Method of fabricating [F-18]FEONM precursor

A contrast agent precursor is revealed. The contrast agent precursor includes a 1,4,7-Tris(carbonylmethyl)-1,4,7,10-tetraazacyclododecane that forms complexes with radioisotopes or connects to a peptide. The contrast agent precursor also includes a 2-nitroimidazole that allows the precursor to become retained in hypoxic tissues According to the features mentioned above, the contrast agent prepared by the precursor has a better binding specificity, labeling accuracy and detection sensitivity. Moreover, a method for preparing the contrast agent precursor not only solves the emulsion problem generated during conventional synthesis of intermediate products but also provides a solution to the problem of residual trifluoroacetic acid. Both the yield rate and the purity of the final product are also improved.

Contrast agent precursor and method for preparing the same

A tetradentate organic ligand H-MN-16Bn containing a long alkyl group, a precursor thereof, and a method for preparing the same are revealed. A precursor of H-MN-16Bn, benzyl 16-bromohexadecanate, is obtained by esterification reaction of 16-bromohexadecanoic acid. Then bimolecular nucleophilic substitution reaction (S2) of Benzyl 16-bromohexadecanate with nitrogen sulfide (NS) is carried out to get H-MN-16Bn that is used as a standard hydrolysis metabolites of non-radioactiveRe-complex compound.

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In a benzodiazepine derivative and a method of producing the derivative, isatoic anhydride or 5-chloroisatoic anhydride is reacted with amino acid ester hydrochloride for conducting a simple cyclization to obtain a produce with a low percentage of by-product directly without requiring the complicated separation and purification processes of column chromatography, and a chlorine-containing structure of the structure can improve the lipo-solubility and chlorine ion permeability and allow a functional group of a radioisotope to be modified to maximize the effects of the pharmacological properties such as the sedative, anticonvulsant and anti-spasmodic effects on the central nervous system or the benzodiazepine derivative can be used as a contrast agent of the system with excellent effects on applications.

Benzodiazepine derivative and method of producing the same

A method for synthesis of 4-OH substituted anabaseine derivative which is used as an &#x3b1;receptor agonist is revealed. A nucleophilic substitution reaction of &#x3b4;-valerolactam with ethyl nicotinate is carried out to get an intermediate product. Then heat the intermediate product under reflux with concentrated hydrochloric acid to get a cyclized product-anabaseine. Next anabaseine and 4-hydroxyethoxy-2-methoxybenzaldehyde are reacted under concentrated hydrochloric acid catalysis to get a 4-OH anabaseine derivative 3-[(4-Hydroxyethoxy-2-methoxy)-benzylidene]anabaseine. The 4-OH anabaseine derivative is synthesized and prepared easily by the present invention. Not only the steps for synthesis are simplified, the yield is as high as 60%. The product can be mass-produced.

Method for synthesis of 4-OH substituted anabaseine derivative

A precursor for labeling therapeutic agents for liver cancer and a method for manufacturing the same are revealed. The chemical structure of the precursor has a ligand linked to complex compounds of radioisotopes. Moreover, the chemical structure of the precursor further includes a specific functional group soluble in Lipiodol or having properties of Lipiodol. Thus the radioisotopes attached to the precursor are allowed to retain in hepatic tissues of patients with liver cancer for internal radiation therapy of liver cancer.

Precursor for labeling therapeutic agent for liver cancer and method for manufacturing the same

A bifunctional compound and a method for manufacturing the same are revealed. The structural formula of the compound includes two main functional groups. One functional group is a diamide dithiolate (NS) ligand able to bind with radioisotopes. The other functional group is polybasic carboxylic acid that binds to biochemical substances. Based on properties of the above two functional groups, the compound of the present invention can be used for preparation of radiopharmaceuticals such as radiotracter for disease diagnosis or radioactive therapeutic agent for disease treatment.

Bifunctional compound and method for manufacturing the same

A precursor used for labeling hepatocyte receptors and applied to radiotracers for imaging or pharmaceutical compositions for liver cancers is revealed. The precursor is a bifunctional compound. The bifunctional group includes a trisaccharide structure and a diamide dimercaptide (NS) ligand. The trisaccharide has high affinity to asialoglycoprotein receptors (ASGPR) on surfaces of hepatocytes while NSligand reacts with radioisotopes to form neutral complexes. Thus the precursor stays on surfaces of hepatocytes to provide radioisotope labeling or treatment effect of liver cancers.

Precursor used for labeling hepatorcyte receptor and containing trisaccharide and diamide demercaptide ligand, method for preparing the same, radiotracer and pharmaceutical composition of the same

A method for preparing a radiotracer precursor SnADAM is revealed. The method overcomes shortcomings of conventional synthesis methods including lower yield rate and time-consuming. Moreover, Pd/C catalyst and hydrogen gas are used to catalyze reduction reaction for avoiding the generation of a large amount of intermediate products with similar structures. Thus there is no need to perform isolation and purification processes. The yield rate of the intermediate products is also increased so that its impact on the low yield rate of the final product SnADAM is minimized. A part of the reaction is significantly accelerated by using tris(dibenzylideneacetone)-dipalladium(0) (Pd(dba)) as a catalyst. Thus the production time of SnADAM is shortened.

Method for preparing radiotracer precursor SnADAM

A method for preparing a precursor used to label hepatocyte receptors is revealed. The precursor contains a bifunctional structure including trisaccharide and DTPA ligand. During synthesis processes of the precursor, silica gel columns and Reverse phase-18 (RP-18) columns are used for purification. Thus both the purification times and cost of each purification are reduced. Moreover, use diethyl ether to facilitate precipitation of products and remove a part of coupling reagent. Removing the coupling reagent helps purification of products. Furthermore, N,N-bis(carboxymethyl)-L-lysine hydrate and benzyl chloroformate are coupled to form a trisaccharide skeleton so as to ensure the yield rate of trisaccharide structure.

Method for preparing precursor used for labeling hepatocyte receptor and containing trisaccharide and DTPA ligand

A radiotracer precursor for imaging of hypoxic tissues, a radiotracer and a method for preparing the same are revealed. The radiotracer precursor, DANI, includes a nitroimidazole functional group with a feature of retention in hypoxic tissues and a bifunctional ligand able to complex with radioisotopes. Thus DANI can be used to produce radiotracers stayed in hypoxic tissues and the radiotracers are applied to medical imaging of malignant tumor with hypoxic layer.

Radiotracer precursor for imaging of hypoxic tissue, radiotracer, and method for preparing the same

The present invention relates to a radiotracer precursor for imaging of hypoxic tissues, a radiotracer and a method for preparing the same. The radiotracer precursor, BANI, includes a nitroimidazole functional group with a feature of retention in hypoxic tissues and a bifunctional ligand able to complex with radioisotopes. Thus BANI can be used to produce radiotracers retained in hypoxic tissues and the radiotracers are applied to medical imaging of malignant tumor with hypoxic layer.

Radiotracer precursor BANI for imaging of hypoxic tissue, radiotracer, and method for preparing the same

A precursor SnBZM for a dopamine receptor radiotracer and a method for preparing the same are revealed. The precursor includes a tributyltin group (BuSn) that is easy to be replaced. Thus a dopamine receptor radiotracerI-IBZM can be produced at high yield rate by a substitution reaction of the precursor. At the same time, both the method for preparing the precursor SnBZM and a method for preparing a reference standard IBZM are simplified. Moreover, stability of each product is improved.

Radiotracer precursor and method for preparing the same

A bifunctional compound with a monosaccharide and a NSligand, and more particularly, a bifunctional compound with a NSligand and aminohexylacetyl galactosamine (ah-GalNAc) is provided. A method for preparing the bifunctional compound with a monosaccharide and a NSligand is also provided, including activating a carboxyl group in an organic ligand, reacting the activated carboxyl group with a galactopyranoside through amidation, and then hydrolyzing. The bifunctional compound of the present invention is widely useful in nuclear medicine for preparation of liver imaging agents for assisting in correct diagnosis of diseases.

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Taoyuan County, Taiwan

Cheng-Fang Hsu