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

Patent metadata

Field	Value
Publication number	US-2019343971-A1
Application number	US-201816200833-A
Country	US
Kind code	A1
Filing date	Nov 27, 2018
Priority date	May 9, 2018
Publication date	Nov 14, 2019
Grant date	—

Abstract

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.

First claim

What is claimed is:

1 . A hexa-lactoside-triazanonane triacetic acid (NOTA) derivative, which 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 (e.g. p-SCN-benzyl-NODA-GA) in the presence of triethyl amine/dimethyl formamide as a solvent.

2 . The hexa-lactoside-NOTA derivative according to claim 1 , wherein the hexa-lactoside is AHA-Asp[DCM-Lys(ah-Lac) 3 ] 2 .

3 . The hexa-lactoside-NOTA derivative according to claim 1 , wherein the NOTA is p-thiocyanate-benzyl-triazanonane diacetic acid-glutamic acid, p-SCN-benzyl-NODA-GA.

4 . A method for radiolabeling a hexa-lactoside positron emission tomography (PET) imaging agent for a liver receptor with Ga-68, comprising reacting 3-valent Ga-68 and a triazanonane triacetic acid (NOTA) conjugate of six chains of lactose with sodium acetate buffer in a freeze drying ampoule at room temperature.

5 . The radiolabeling method according to claim 4 , wherein the reaction at room temperature is continued for 15 min.

6 . The radiolabeling method according to claim 4 , wherein the reaction at room temperature takes place at pH 4-5.

7 . The radiolabeling method according to claim 4 , wherein the finish labeled product is hexa-lactoside-thiocyanate-benzyl-triazanonane diacetic acid-glutamic acid chelated with Ga-68.

8 . The radiolabeling method according to claim 4 , wherein the hexa-lactoside-thiocyanate-benzyl-triazanonane diacetic acid-glutamic acid in the labeled product is chelated with Ga-68 by 6 coordination bonds.

9 . A hexa-lactoside positron emission tomography (PET) imaging agent for a liver receptor, having a structure of:

10 . The imaging agent according to claim 9 , which is prepared by the steps of:
reacting 3-valent Ga-68 and a triazanonane triacetic acid (NOTA) conjugate of six chains of lactose with sodium acetate buffer in a freeze drying ampoule at room temperature.

Assignees

• Iner Aec Executive Yuan

Inventors

• Lin Wuu-Jyh
• Wang Mei-Hui
• Yu Hung-Man
• Lin Kun-Liang
• Jiang yan-feng
• Chen rui-yu

Classifications

• C07H15/04

  attached to an oxygen atom of the saccharide radical · CPC title

• C07B59/005

  Sugars; Derivatives thereof; Nucleosides; Nucleotides; Nucleic acids · CPC title

• C07H15/06

  being a hydroxyalkyl group esterified by a fatty acid · CPC title

• A61K51/0497 Primary

  conjugates with a carrier being an organic compounds · CPC title

• C07B2200/05

  Isotopically modified compounds, e.g. labelled · CPC title