QUANTIFICATION METHOD FOR REMAINING LIVER FUNCTION AND NOVEL LIVER RECEPTOR IMAGING AGENT

• US 20110097265A1
• Filed: 05/13/2010
• Published: 04/28/2011
• Est. Priority Date: 10/26/2009
• Status: Active Grant

• Current Assignee: Institute Of Nuclear Energy Research Atomic Energy Council Executive Yuan
• Original Assignee: Institute Of Nuclear Energy Research Atomic Energy Council Executive Yuan
• Inventors: Lin, Wuu-Jyh, Chien, Chuan-Yi, Yu, Hung-Man, Wang, Mei-Hui, Lee, Reiko Takasaka, Lee, Yuan-Chuan
• Granted Patent: US 8,435,491 B2
• Time in Patent Office: Days
• US Class Current: 424/1.69
• CPC Class Codes: A61K 51/0491 Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers
• CPC Class Codes: A61K 51/0497 conjugates with a carrier being an organic compounds
• CPC Class Codes: C07H 15/04 attached to an oxygen atom of the saccharide radical

Abstract

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.

Claims

1. A quantification method for remaining liver function, using in vivo molecular imaging with SPECT/CT.

2. The method according to claim 1, comprising:

(a) intravenously injecting a radiation dose of 200 nCi/g of a liver receptor imaging agent;

(b) measuring the radioactivity per square unit of liver with a SPECT medical imaging instrument at a specific fixed time;

(c) taking the radioactivity absorbed by liver in a normal group as 100% of remaining liver function; and

(d) determining the relative remaining liver function by comparing the radioactivity absorbed by liver in each disease group with that in the normal group.

3. The method according to claim 2, wherein when the remaining liver function is lower than 25%, a liver transplantation is necessary.

4. A liver receptor imaging agent, with a lysine based nitrilo triacetic acid structure as backbone which polymerizes with saccharide groups, to bind with a galactosamine chain or lactose chain, and having a free amino group to be attached to a radioisotope by derivatization.

5. The liver receptor imaging agent according to claim 4, wherein the liver receptor imaging agent is prepared by directly adding the trivalent radioisotope In-111 into DTPA-DCM-Lysine hexa-lactoside, and reacting at room temperature with shaking for 15 min.

6. The liver receptor imaging agent according to claim 5, wherein both labeling yield and radiochemical purity of the liver receptor imaging agent are higher than 99%, no addition of oxidant and purification are required, and the specific radioactivity is 2.5×

10¹⁰ Bq/mg.

7. The liver receptor imaging agent according to claim 4, wherein the liver receptor imaging agent polysaccharide chain is selected from the group consisting of In-111-DTPA-AHA-Asp[DCM-Lys(ah-Lac)₃]₂, In-111-DTPA-DCM-Lys(ahGalNAc)₃, and In-111-DTPA-Lys(GahGalNAc)₃.

8. The liver receptor imaging agent according to claim 4, wherein only 200 nCi/g of the liver receptor imaging agent is required, to obtain a clear image.

9. The liver receptor imaging agent according to claim 4, wherein the liver receptor imaging agent is merely accumulated in liver.

10. The liver receptor imaging agent according to claim 4, wherein the radioelement is selected from the group consisting of In-111, Tc-99m, Ga-68, Gd, and a fluorescent agent.

11. The liver receptor imaging agent according to claim 4, wherein ε

-benzyloxycarbonyl-α

-dicarboxylmethyl-L-lysine (Z-DCM-Lys) is used as the basic structure to be connected to aminohexyl β

-GalNAc (ah-GalNAc), glycyl-aminohexyl β

-GalNAc (Gah-GalNAc), or aminohexyl Lac (ah-Lac) in series, so as to form a three-chain glycopeptides, followed by attachment to the radioisotope through derivatization of the free amino group.

12. The liver receptor imaging agent according to claim 11, wherein when a lactose chain is connected in series, two molecules of three-chain lactoside are connected together with aspartic acid or glutamic acid in series, that is, two molecules of ε

-Z-α

-DCM-Lys (ah-Lac)₃ are connected together with aminohexanoic aspartic acid (AHA-Asp) in series, to form AHA-Asp [DCM-Lys(ah-Lac)₃]₂ (hexa-Lactoside).

13. The liver receptor imaging agent according to claim 12, wherein the free amino group end of the hexa-Lactoside reacts with DTPA anhydride in a sodium carbonate solution, to form a DTPA derivative of AHA-Asp[DCM-Lys(ah-Lac)₃]₂.

14. The DTPA derivative according to claim 13, being suitable for labeling with In-111, Tc-99m, Ga-68, Gd, or a fluorescent material.