Novel grp-r agonistic 177-lutetium-labeled bombesin derivatives for diagnosis and treatment of prostate cancer

Patent metadata

Field	Value
Publication number	US-2016121004-A1
Application number	US-201514657802-A
Country	US
Kind code	A1
Filing date	Mar 13, 2015
Priority date	Jun 16, 2014
Publication date	May 5, 2016
Grant date	—

Abstract

Provided is a novel compound capable of being usefully used to diagnose and treat prostate cancer by labeling a radioisotope on a bombesin derivatives capable of selectively targeting a target material over-expressed in tumor cells in order to develop an effective diagnose and treatment method of diseases associated with prostate cancer.

First claim

What is claimed is:

1 . A bombesin derivatives represented by the following Chemical Formula 1.

[In Chemical Formula 1,
n is an integer of 1 to 3,
X is a metal chelator,
Y is a spacer linking the metal chelator X and a bombesin derivatives agonist, A, and
A is a bombesin derivatives agent represented by the following sequence.]
A: *-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH 2

2 . The bombesin derivatives of claim 1 , wherein X includes one or more radioactive metal nuclides and is a metal chelator for a trivalent metal.

3 . The bombesin derivatives of claim 2 , wherein the metal chelator for the trivalent metal is a DOTA-based chelator.

4 . The bombesin derivatives of claim 2 , wherein the radioactive metal nuclide is for radiotherapy and is selected from the group consisting of 176 Yb, 111 In, 169 Gd, 177 Lu, 105 Rh, 111 Ag, 64 Cu, 67 Ga, 68 Ga, 125 I, 123 I, 129 I, and 166 Ho.

5 . The bombesin derivatives of claim 1 , wherein it is a compound represented by the following Chemical Formula 2.

[In Chemical Formula 2,
n is an integer of 1 to 3,
m is an integer of 1 to 5,
R 1 to R 2 are each independently hydrogen or (C1-C5)alkyl, and
G is a glucose group or an derivatives thereof.]
A: *-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH 2

6 . The bombesin derivatives of claim 5 , wherein in Chemical Formula 2, n is 3 and R 1 and R 2 are hydrogen.

7 . The bombesin derivatives of claim 5 , wherein G is

R 3(s) are each independently hydrogen or a hydroxyl group.

8 . A preparation method of a bombesin derivatives comprising synthesizing a compound represented by the following Chemical Formula 2.

[In Chemical Formula 2,
n is an integer of 1 to 3,
m is an integer of 1 to 5,
X is a metal chelator,
R 1 to R 2 are each independently hydrogen or (C1-C5)alkyl,
A is *-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2, and
G is a glucose group or derivatives thereof]

9 . A composition for diagnosis and treatment of diseases associated with the prostate comprising the bombesin derivatives of claim 1 .

Assignees

• Korea Atomic Energy Res

Inventors

• Lim Jae Cheong
• Cho Eun Ha
• Kim Jin Joo
• Choi Sang Mu
• Lee So-Young
• Park Ul Jae
• Nam Sung Soo

Classifications

• C07K14/57572

  Gastrin releasing peptide (bombesin C07K7/086) · CPC title

• C07K14/00

  Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof · CPC title

• A61K51/088

  conjugates with carriers being peptides, polyamino acids or proteins (antibodies A61K51/10) · CPC title

• A61K49/106

  the complex-forming compound being cyclic, e.g. DOTA · CPC title

• A61K51/0482

  chelates from cyclic ligands, e.g. DOTA · CPC title