Molecular Probe for Imaging of Pancreatic Islets and Use of the Same

a technology of pancreatic islets and probes, which is applied in the field of molecular probes for imaging of pancreatic islets, can solve the problems of diabetes already reaching the stage of too difficult treatment, unsatisfactory effects, and possible too late intervention stag

Inactive Publication Date: 2014-05-08
ARKRAY INC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

Enables specific accumulation in pancreatic islets, providing enhanced contrast and enabling the early detection and diagnosis of diabetes by quantifying pancreatic islet amounts before glucose tolerance abnormalities occur.

Problems solved by technology

As a measure against this increase, interventions for preventing diabetes from developing have been made based on the glucose tolerance test, resulting, however, in unsatisfactory effects.
The cause is as follows: at such a borderline stage that functional abnormalities are found by the glucose tolerance test, disorders of pancreatic islets have already advanced to a high degree, and this stage possibly is too late as a time for starting interventions.
Therefore, when functional abnormalities are detected or there are subjective symptoms, diabetes has already reached the stage where it is too difficult to be treated.

Method used

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  • Molecular Probe for Imaging of Pancreatic Islets and Use of the Same
  • Molecular Probe for Imaging of Pancreatic Islets and Use of the Same
  • Molecular Probe for Imaging of Pancreatic Islets and Use of the Same

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0212]Using the molecular probe of the formula (31) below (SEQ ID NO. 31), having a configuration in which an amino group of a side chain of a lysine residue at position 4 was labeled with [125I] 3-iodobenzoyl group (hereinafter referred to also as “[125I]IB label”) and a carboxyl group at a C-terminus was amidated in the sequence of SEQ ID NO. 1, biodistribution of the same in a mouse was determined. First, the molecular probe of the formula (31) below was prepared in the following manner.

[0213][Preparation of Molecular Probe]

[0214]Polypeptide synthesis was performed by using an automatic peptide synthesizer (Model 433A) manufactured by Applied Biosystems, in accordance with the attached software. For the amino acids having functional groups at the side chains, Asp(OBu), Ser(OBu), Lys(Boc), Gln(Trt), Glu(OBu), Arg(Pbf), Asn(Trt) and Trp(Boc) were used respectively. For a lysine at position 19, Lys(Mmt) was used. Rink Amide MBHA (0.125 mmol, 0.34 mmol / g) was employed as the starting...

example 2

[0238]Using the molecular probe of the formula (35) below (SEQ ID NO. 35), having a configuration in which an α-amino group at an N-terminus was labeled with [125I]3-iodobenzoyl group and a carboxyl group at a C-terminus is amidated in the sequence of SEQ ID NO. 5, biodistribution of the same in a mouse was determined. The molecular probe of the formula (35) below was prepared in the same manner in Example 1 except that an amino group labeled was an α-amino group at an N-terminus.

[0239][Biodistribution]

[0240]The molecular probe thus prepared of the formula (35) (0.58 μCi) was administered to unanesthetized 6-week-old ddY mice (male, weight: 30 g) by intravenous injection (through the tail vein). At points of 5 minutes, 15 minutes, 30 minutes, 60 minutes, and 120 minutes after the administration, organs were dissected out of the mice, respectively (n=5). The weight and the radioactivity of each organ were determined, and an accumulation amount (% dose / g) of the molecular probe was ca...

example 3

[0250]Using a molecular probe of the formula (36) below (SEQ ID NO. 36), having a configuration in which an amino group of a side chain of a lysine residue at position 4 was labeled with 3-([123I] iodobenzoyl group (hereinafter referred to also as “[125I]IB label”) and a carboxyl group at a C-terminus is amidated in the sequence of SEQ ID No. 1, biodistribution of the same in a mouse was determined. The molecular probe of the formula (36) below was prepared in the same manner as in the case of the molecular probe of the aforementioned formula (31) using the molecular probe precursor of the aforementioned formula (31) except that [123I]SIB was used in place of [125I]SIB.

[0251][Three-Dimensional Imaging]

[0252]Using the prepared molecular probe of the aforementioned formula (36), SPECT imaging was carried out. The prepared molecular probe of the formula (36) (498 μCi) was administered to anesthetized 5-week-old ddy mice (male, weight: 25 g) by intravenous injection, and the SPECT imagi...

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Abstract

To provide a molecular probe for imaging of pancreatic islets. A molecular probe for use in imaging of pancreatic islets is provided. The molecular probe includes any one of the following polypeptides: polypeptides represented by the following formulae (1), (5), and (9); and polypeptides having homology with the foregoing polypeptides:Z-DLSXQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2 (1)Z-DLSKQMEEEAVRLFIEWLXNGGPSSGAPPPS-NH2 (5)B-DLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2 (9)where X in the formulae (1) and (5) and B- in the formula (9) indicate that an amino group is labeled with a group represented by the formula (I) below having an aromatic ring,wherein A represents either an aromatic hydrocarbon group or an aromatic heterocyclic group, R1 represents a substituent that contains radioactive iodine, R2 represents either a hydrogen atom or a substituent different from that represented by R1, and R3 represents any one of a bond, a methylene group, and an oxymethylene group.

Description

TECHNICAL FIELD[0001]The present invention relates to a molecular probe for imaging of pancreatic islets, and relates to use of the same.BACKGROUND ART[0002]Today, type-II diabetics are continuously increasing in Japan, and the estimated number of the same exceeds 8,200,000. As a measure against this increase, interventions for preventing diabetes from developing have been made based on the glucose tolerance test, resulting, however, in unsatisfactory effects. The cause is as follows: at such a borderline stage that functional abnormalities are found by the glucose tolerance test, disorders of pancreatic islets have already advanced to a high degree, and this stage possibly is too late as a time for starting interventions.[0003]More specifically, in the diabetes developing process, the amount of pancreatic islets (particularly, the amount of pancreatic β-cells) decreases prior to the occurrence of glucose tolerance abnormalities. Therefore, when functional abnormalities are detected...

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): A61K51/08
CPCA61K51/088A61P3/10A61K38/16A61K49/06A61K49/14
InventorINAGAKI, NOBUYASAJI, HIDEOTOYODA, KENTAROKIMURA, HIROYUKIOGAWA, YU
OwnerARKRAY INC