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

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

The Johns Hopkins University

Atomic Energy Council-institute of Nuclear Energy Research

Institute of Nuclear Energy Research

Mei-Hui Wang

Wuu-Jyh Lin

Hung-Man Yu

Chuan-Yi Chien

Kun-Liang Lin

Yuan-Chuan Lee

Jen-Tsung Wang

Ping-Yen Wang

Reiko Takasaka Lee

Mao-Chi Weng

Yan-Feng Jiang

Rui-Yu Chen

Chia-Yu Hu

Chun-Hung Yang

Cheng-Fang Hsu

Yu Lung Chang

Po-Jung Chen

Lie-Hang Shen

Chih-Yuan Lin

Chien-Chung Hsia

Shui-Cheng Lee

Chun-Hao Tseng

Haw-Jan Chen

Jyun-Hong Chen

Wei-Ti Kuo

Hung-Wen Yu

Disclosed herein is a process for chemically synthesizing of hydroquinone derivatives, especially for hydroquinone derivatives with heptadecatrienyl side chain, which is synthesized via a Wittig reaction of 2-(10'-oxononyl)-1,4-diacetoxyl benzene and (3E, 5Z)-3,5-heptadien-1-triphenylphosphonium iodide and then deacetylation. In addition, the product is solid powder.

Process for synthesizing of hydroquinone derivatives with heptadecatrienyl side chain

The present invention provides a hexa-lactoside-triazanonane triacetic acid (NOTA) derivative, a method for radiolabeling a hexa-lactoside positron emission tomography (PET) imaging agent for a liver receptor with Ga-68, and a hexa-lactoside PET imaging agent for a liver receptor. The hexa-lactoside-NOTA derivative is a conjugate of six chains of lactose with NOTA obtained by conjugating hexa-lactoside to a chelating agent p-thiocyanate-benzyl-triazanonane diacetic acid-glutamic acid in the presence of triethyl amine/dimethyl formamide as a solvent. The radiolabeling method comprises labeling with Ga-68 at room temperature. According to the present invention, the labeling effect is stable, the labeling efficiency of the labeled product is greater than 95%, the labeled product is highly stable and the radiochemical purity is still greater than 90% after 4 hours.

Hexa-lactoside-triazanonane triacetic acid (NOTA) derivative, method for radiolabeling hexa-lactoside positron emission tomography (PET) imaging agent for liver receptor with Ga-68, and hexa-lactoside PET imaging agent for liver receptor

The present invention relates to a hydroxamic acid-based contrast agent containing an isotope of fluorine, which comprises a compound having a structure of Formula (III):  wherein Rrepresents radioactive fluorine-18 (F) or isotope fluorine-19 (F), and Rrepresents hydroxyamine &#x2014;(NH)OH. The hydroxamic acid-based contrast agent containing an isotope of fluorine provided in the present invention has the capability of selectively inhibiting histone deacetylase (HDAC) subtypes 8/6/3, and specifically targets to the focus of spinocerebellar ataxia with over-activation of HDAC. By labeling with the radioisotope fluorine-18, a positron emission tomography (PET) image is obtained with the hydroxamic acid-based contrast agent containing radioisotope fluorine-18, whereby spinocerebellar ataxia is effectively detected. Therefore, the hydroxamic acid-based contrast agent containing an isotope of fluorine provided in the present invention is potentially useful as a probe for early diagnosis and evaluation of the therapeutic effect of spinocerebellar ataxia.

Hydroxamic acid type contrast agent containing radioisotope fluoride, preparation method and application thereof

Disclosed herein are a multivalent saccharide complex, a radioactive multivalent saccharide complex contrast agent and use thereof. The multivalent saccharide complex has a chelator, a linker, and glucose, and is configured to diagnose and evaluate the therapeutic effect of cancers.

Multivalent saccharide complex, radioactive multivalent saccharide complex contrast agent, and use thereof

Disclosed herein are a novel polymer, a thermosensitive carrier prepared using the same and use thereof. The novel polymer is essentially composed of a PEO-PPO-PEO block copolymer and silane.

Polymer, thermosensitive carrier and use thereof

The present invention provides a method for preparing a 6-aminohexyl lactoside-NOTA conjugate. The preparation method comprises brominating perbenzoylated lactose with hydrobromic acid; glycosylating 6-azidohexanol to obtain 6-azidohexyl perbenzoyl lactoside; and deprotecting this precursor in two steps to obtain 6-aminohexyl lactoside and conjugating 6-aminohexyl lactoside to NCS-benzyl-NODA GA (i.e. 2,2'-(7-(1-carboxy-4-((4-isothiocyanate benzyl) amino)-4-oxobutyl)-1,4,7-triazonane-1,4-diyl) diacetic acid) in triethyl amine as an alkaline solvent, to obtain a 6-aminohexyl lactoside-NCS-benzyl-NODA GA conjugate. In this novel preparation method, no deglycosylated side product is produced, such that the yield is considerably increased to 46%. Therefore, the method is suitable for future massive production since the requirement for repeated preparations for massive production is reduced, and the impurities produced in the previously scaled-up preparation process are not present.

Method for preparing 6-aminohexyl lactoside-NOTA conjugate

The invention discloses a high-yield method for preparing a ribonucleic acid (RNA)-diethyltriamine pentaacetic acid (DTPA) conjugate. The conjugate is prepared by conjugating a RNA or locked nucleic acid (LNA) having an amino group to p-isothiocyanate benzyl-DTPA (SCN-Bn-DTPA) or DTPA anhydride with heating under microwave.

High-yield method for rapidly conjugating ribonucleic acid (RNA) to diethylenetriamine pentaacetic acid (DTPA)

A test indicator for quantifying remaining liver function is provided. A novel liver receptor imaging agent with liver targeting property is utilized to develop a method for quantifying remaining liver function to serve as test indicator for judging the liver failure outcome in clinic, particularly for judging the necessity of liver transplantation for patients with liver failure or liver disease. The radioactivity uptake of the test indicator was negatively correlated with the extent of liver reserve. The cutoff value of liver reserve for liver transplantation is also disclosed.

Quantification method for remaining liver function and novel liver receptor imaging agent

A novel gall bladder image agent which includes a radio-labelled MAG3-tri-galactosamine, and its preparation method, which includes reacting mercaptoacetyltriglycine (MAG3)-tri-galactosamine, SnF2 and Tc-99m in the presence of a phosphate buffer solution (at pH of from 10.0&#x2dc;12.0) to obtain Tc-99m-MAG3-tri-galactosamine, when the MAG3-tri-galactosamine is MAG3-DCM-Lys(Gah-GalNAc)3 (where DCM represents a dicarboxymethyl group, and Gah represents a glycine-aminohexyl group), it obtains a labelling yield of at least 90%, and its specific radioactivity is at least 7.0&#xd7;109 Bq/mg.

Gall bladder imaging agent and its preparation method

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

The present invention is related to a pharmaceutical composition for a liver-receptor imaging injection, the pharmaceutical composition including a bi-functional compound which has a ASGPR specificity, wherein the bi-functional compound includes a backbone of alpha-amino acid (or the derivatives thereof) and a poly-galactosamine chain (or a poly-lactose chain) connected to the alpha-amino acid. Thereby, the pharmaceutical composition can quantify potential of liver storage ability and evaluate severity of the course of liver disease. A liver-receptor imaging injection using the same and the one-step dispensing method thereof are also provided to improve defects of iodine-labeled and overcome disadvantages of the reduced labeling-yield and the instability after autoclave sterilization.

Liver-receptor imaging injection, dispensing method and pharmaceutical composition thereof

This invention provides novel liver targeting agents and their synthetic methods. A liver targeting agent, with a lysine based nitrilotriacetic acid structure as backbone which acquires multivalency with saccharide groups, to bind with a galactosamine chain or lactose chain is disclosed. In particular, only one amino acid L-lysine is involved to provide trivalency. All carboxyl groups in N-benzyloxycarbonyl-N-dicarboxymethyl-L-lysine can be conjugated with three glycosides of ahGalNAc or ahLac in one step. This invention also provides a hexa-lactoside. In particular, the TFA-AHA-Asp was used to conjugate 2 molecules of NTA(ahLac). This invention also provides a method for adding a spacer between NTA and DTPA. The extended hepatocyte-specific glyco-ligand has higherIn-radiolabelling yield than those non-extended.

Liver-targeting agents and their synthesis

The invention discloses one glyco-molecular imaging method for grade classification of liver fibrosis and its glyco-molecular imaging agent. The agent combining with glyco-molecular imaging method for liver targeting could be used to differentiate the grade of liver fibrosis and follow-up evaluation of the therapeutic effect.

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Taoyuan, Taiwan

Mei-Hui Wang