Molecular probe for imaging of pancreatic islets and use of the same

Patent metadata

Field	Value
Publication number	US-9238083-B2
Application number	US-89389610-A
Country	US
Kind code	B2
Filing date	Sep 29, 2010
Priority date	Sep 30, 2009
Publication date	Jan 19, 2016
Grant date	Jan 19, 2016

Abstract

A molecular probe for imaging of pancreatic islets is provided. The molecular probe includes a polypeptide represented by the following formula (1), or a polypeptide that has a homology with the foregoing polypeptide.
(SEQ ID NO. 1) Z-HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPSX-NH 2  (1)
Wherein “X” represents a lysine residue, an amino group of a side chain of the lysine residue being labeled with a group represented by the following chemical formula (I),

wherein A represents an aromatic hydrocarbon group or an aromatic heterocyclic group; R 1 represents a substituent that contains 11 C, 13 N, 15 O, 18 F, 64 Cu, 67 Ga, 68 Ga, 75 Br, 76 Br, 77 Br, 99m Tc, 111 In, 123 I, 124 I, 125 I, or 131 I; R 2 represents either a hydrogen atom, or a substituent different from that represented by R 1 ; and R 3 represents any one of a bond, an alkylene group having 1 to 6 carbon atoms, and an oxyalkylene group having 1 to 6 carbon atoms.

First claim

The invention claimed is:

1. A precursor of a molecular probe for imaging of pancreatic islets, the precursor being used for producing a molecular probe for imaging of pancreatic islets, the precursor comprising any one of the following polypeptides:
a polypeptide represented by the following formula (2);
a polypeptide obtained by deletion, insertion, or substitution of one to three amino acids with respect to the polypeptide represented by the following formula (2) and capable of binding to pancreatic islets after being labeled and deprotected; and
a polypeptide having a homology of 95% or higher with the amino acid sequence of the polypeptide represented by the following formula (2) and capable of binding to pancreatic islets after being labeled and deprotected,

(SEQ ID NO. 2)

*-HGEGTFTSDLSK*QMEEEAVRLFIEWLK*NGGPSSGAPPPSK-NH 2

(2)

wherein:
“*-” indicates that an α-amino group at an N-terminus is protected by a protecting group, or is modified with a modifying group having no electric charge,
“K*” indicates that an amino group of a side chain of a lysine is protected by a protecting group,
“—NH 2 ” indicates that a carboxyl group at a C-terminus is amidated, and
the functional groups of the side chains of the amino acids except for K* are not protected by a protecting group.

2. A method for producing a molecular probe for imaging of pancreatic islets, the method comprising:
labeling and deprotecting the precursor of a molecular probe for imaging of pancreatic islets according to claim 1 .

3. The method for producing a molecular probe for imaging of pancreatic islets according to claim 2 ,
wherein the labeling of the precursor of a molecular probe for imaging of pancreatic islets includes labeling of the precursor with a compound having a group represented by the following chemical formula (I),

wherein:
A represents an aromatic hydrocarbon group or an aromatic heterocyclic group,
R 1 represents a substituent containing 11 C, 13 N, 15 O, 18 F, 75 Br, 76 Br, 77 Br, 123 I, 124 I, 125 I, or 131 I,
R 2 represents either a hydrogen atom, or one or more substituents different from that represented by R 1 , and
R 3 represents any one of a bond, an alkylene group having 1 to 6 carbon atoms, and an oxyalkylene group having 1 to 6 carbon atoms.

4. A method for imaging pancreatic islets, the method comprising
producing a molecular probe for imaging of pancreatic islets by labeling and deprotecting the precursor of a molecular probe for imaging of pancreatic islets according to claim 1 , and
detecting a signal of the molecular probe for imaging of pancreatic islets, the molecular probe being preliminarily bound to the pancreatic islets.

5. The method for imaging pancreatic islets according to claim 4 , the method further comprising determining a state of pancreatic islets on the basis of results of the imaging of pancreatic islets using the molecular probe for imaging of pancreatic islets.

6. A method for determining an amount of pancreatic islets, the method comprising:
detecting a signal of the molecular probe for imaging of pancreatic islets obtained by the method according to claim 2 , the molecular probe being preliminarily bound to pancreatic islets; and
calculating an amount of pancreatic islets from the detected signal of the molecular probe for imaging of pancreatic islets.

7. The method for determining an amount of pancreatic islets according to claim 6 , further comprising presenting the calculated amount of pancreatic islets.

8. The precursor according to claim 1 , where in the formula (2), “K” indicates that an amino group of a side chain of a lysine is not modified.

9. The precursor according to claim 1 , wherein the precursor comprises the polypeptide represented by the formula (2).

10. The precursor according to claim 1 , wherein the precursor consists of the polypeptide represented by the formula (2).

11. The precursor according to claim 1 , wherein the precursor comprises the polypeptide obtained by deletion, insertion, or substitution of one amino acid with respect to the polypeptide represented by the formula (2).

12. The precursor according to claim 1 , wherein the precursor comprises the polypeptide obtained by deletion, insertion, or substitution of two amino acids with respect to the polypeptide represented by the formula (2).

13. The precursor according to claim 1 , wherein the precursor comprises the polypeptide having a homology of 95% or higher with the amino acid sequence of the polypeptide represented by the formula (2).

14. A kit for imaging of pancreatic islets, the kit comprising a precursor of a molecular probe comprising any one of the following polypeptides:
a polypeptide represented by the following formula (2);
a polypeptide obtained by deletion, insertion, or substitution of one to several amino acids with respect to the polypeptide represented by the following formula (2) and capable of binding to pancreatic islets after being labeled and deprotected; and
a polypeptide having a homology of 80% or higher with the amino acid sequence of the polypeptide represented by the following formula (2) and capable of binding to pancreatic islets after being labeled and deprotected,

(SEQ ID NO. 2)

*-HGEGTFTSDLSK*QMEEEAVRLFIEWLK*NGGPSSGAPPPSK-NH 2

(2)

wherein:
“*-” indicates that an α-amino group at an N-terminus is protected by a protecting group, or is modified with a modifying group having no electric charge,
“K*” indicates that an amino group of a side chain of a lysine is protected by a protecting group, and
“—NH 2 ” indicates that a carboxyl group at a C-terminus is amidated.

15. The kit according to claim 14 , wherein the precursor of the molecular probe included in the kit is in a form of a parenteral solution.

Assignees

• Saji Hideo
• Inagaki Nobuya
• Toyoda Kentaro
• Kimura Hiroyuki
• Hirao Konomu
• Nagakawa Kenji
• Matsuda Hirokazu
• Univ Kyoto
• Arkray Inc

Inventors

• Saji Hideo
• Inagaki Nobuya
• Toyoda Kentaro
• Kimura Hiroyuki
• Hirao Konomu
• Nagakawa Kenji
• Matsuda Hirokazu

Classifications

• A61K51/08 Primary

  Peptides, e.g. proteins {, carriers being peptides, polyamino acids, proteins} · CPC title

• G01T1/161

  Applications in the field of nuclear medicine, e.g. in vivo counting {(apparatus for radiation diagnosis A61B6/00)} · CPC title

• A61K49/06

  Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations · CPC title

• A61K38/16

  Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof {(enzyme inhibitors A61K38/005)} · CPC title

• A61K51/00 Primary

  Preparations containing radioactive substances for use in therapy or testing in vivo · CPC title