# US 9,517,278 B2 · Compound and photoacoustic imaging contrast medium containing the compound

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- Number: US 9,517,278 B2
- Document ID: US9517278B2
- Status: Granted
- Kind: B2
- Application number: 14/413,399
- Filed: 2013-07-17
- Published: 2015-06-18
- Granted: 2016-12-13
- Earliest claimed: 2012-07-20
- Assignees: Canon Kabushiki Kaisha
- Applicants: Canon Kabushiki Kaisha
- Inventors: Atsushi Takahashi; Fumio Yamauchi; Masato Minami; Satoshi Ogawa; Kengo Kanazaki; Satoshi Yuasa
- Web page: https://patentgrep.com/patent/US9517278B2

## CPC

- A61K 49/221: {characterised by the targeting agent or modifying agent linked to the acoustically-active agent}
- A61K 49/0034: {Indocyanine green, i.e. ICG, cardiogreen}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

The present invention provides a photoacoustic imaging contrast medium which exhibits a high degree of accumulation into a tumor even when some extent of time has passed after performing administration and which facilitates an increase in the intensity of photoacoustic signal produced by the tumor. A compound produced by covalent-bonding of an organic dye which absorbs light in the near-infrared wavelength region and a PEG having a branch.

## Claims

### Claim 1

A compound represented by any one of formula (1) to formula (6):
wherein, in the formula (1), A1 represents an organic dye which absorbs light in a near-infrared wavelength region, L1 represents a linker part which is any one of —NH—, —CO—, —O—, and —S— or which contains at least one of —NH—, —CO—, —O—, and —S—, q represents an integer of 1 to 5, m and n represent independently an integer of 10 or more and 2,500 or less, and R1 and R2 represent independently an alkyl group having 1 to 5 carbon atoms,
wherein, in the formula (2), A1 represents an organic dye which absorbs light in the near-infrared wavelength region, L1 represents a linker part which is any one of —NH—, —CO—, —O—, and —S— or which contains at least one of —NH—, —CO—, —O—, and —S—, p and q represent independently an integer of 1 to 5,1, m, and n represent independently an integer of 10 or more and 2,500 or less, and R1 and R2 represent independently an alkyl group having 1 to 5 carbon atoms,
wherein, in the formula (3), A1 represents an organic dye which absorbs light in the near-infrared wavelength region, L1 represents a linker part which is any one of —NH—, —CO—, —O—, and —S— or which contains at least one of —NH—, —CO—, —O—, and —S—, q represents an integer of 1 to 5,1, m, and n represent independently an integer of 10 or more and 2,500 or less, and R1 and R2 represent independently an alkyl group having 1 to 5 carbon atoms,
wherein, in the formula (4), A1 and A2 represent independently an organic dye which absorbs light in the near-infrared wavelength region, L1 and L2 represent independently a linker part which is any one of —NH—, —CO—, —O—, and —S— or which contains at least one of —NH—, —CO—, —O—, and —S—, p, q and r represent independently an integer of 1 to 5, m and n represent independently an integer of 10 or more and 2,500 or less, and R1 and R2 represent independently an alkyl group having 1 to 5 carbon atoms,
wherein, in the formula (5), A1, A2, A3, and A4 represent independently an organic dye which absorbs light in the near-infrared wavelength region, L1, L2, L3, and L4 represent independently a linker part which is any one of —NH—, —CO—, —O—, and —S— or which contains at least one of —NH—, —CO—, —O—, and —S—, p and q represent independently an integer of 1 to 5, and n represents an integer of 10 or more and 2,500 or less, and
wherein, in the formula (6), A1 represents an organic dye which absorbs light in the near-infrared wavelength region, L1 represents a linker part which is any one of —NH—, —CO—, —O—, and —S— or which contains at least one of —NH—, —CO—, —O—, and —S—, p and q represent independently an integer of 1 to 5, and n represents an integer of 10 or more and 2,500 or less wherein, in the formulae (1) to (6), A1, A2, A3, and A4 are independently represented by any one of formulae (7) and (8):
wherein, in the formula (7) and in the formula (8), the symbol * represents a bond with any one of L1, L2, L3, and L4 in the formulae (1) to (6),
wherein, in the formula (7) and in the formula (8), Z forms a cyclic aromatic ring composed of a benz[e]indole ring, benz[f]indole ring, or benz[g]indole ring together with a hydrogen atom, a sulfonate group, or an indole ring bonded to Z, and furthermore, a hydrogen atom of the cyclic aromatic ring may be substituted with an alkyl group having 1 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, or a sulfonate group,
wherein, in the formula (7) and in the formula (8), R3 represents any one of an alkyl group having 1 to 10 carbon atoms and —(CH2)b—SO3− where b represents an integer of 1 to 10, and when R3 is an alkyl group, a halogen ion or an organic acid ion may be contained as a counter ion, and R4 and R5 represent independently any one of a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, —(CH2)b—-SO3−, where b represents an integer of 1 to 10, and —(CH2)b—SO3X, where b represents an integer of 1 to 10 and X represents any one of sodium, potassium, ammonium, triethylammonium, lysine, and arginine,
wherein, in the formula (7) and in the formula (8), a represents an integer of 1 to 10 and s represents 2 or 3, and
wherein, in the formula (8), R6 represents any one of an alkyl group having 1 to 10 carbon atoms, —(CH2)b—SO3−, where b represents an integer of 1 to 10, —(CH2)b—SO3X where b represents an integer of 1 to 10 and X represents any one of sodium, potassium, ammonium, triethylammonium, lysine, and arginine.

### Claim 2 (depends on 1)

The compound according to claim 1, further comprising a capture molecule.

### Claim 3 (depends on 1)

The compound according to claim 1, wherein, in the formulae (1) to (6), at least one linker part of L1 to L4 is a polypeptide or a single-chain antibody.

### Claim 4 (depends on 1)

The compound according to claim 1, wherein, in the formulae (1) to (6), at least one of L1 to L4 is represented by formula (46):
where L5 represents a polypeptide or a single-chain antibody, —NH— represents a bond through an amino group of an amino acid in the polypeptide or the single-chain antibody, —S— represents a bond through a thiol group of an amino acid in the polypeptide or the single-chain antibody, L6 represents an alkyl chain having 1 to 10 carbon atoms and including any one of a carbonyl group, an amide group, an ester group and a piperazyl group, ** represents a bond with at least one of A1 to A4, *** represents a bond with the alkyl chain side or the ethylene glycol chain side of the formulae (1) to (6).

### Claim 5 (depends on 4)

The compound according to claim 4, wherein, in the formula (46), L6 is —(CH2)2—C(═O)—NH—, where the ethylene group side is bonded to a nitrogen atom of a maleimide group and the amide group side is bonded at ***.

### Claim 6 (depends on 1)

The compound according to claim 1, wherein the compound is suitable for imaging a tumor.

### Claim 7 (depends on 1)

The compound according to claim 1, wherein the compound is suitable for imaging a lymph node.

### Claim 8 (depends on 1)

A photoacoustic imaging contrast medium comprising the compound according to claim 1 and a dispersion medium.

### Claim 9 (depends on 8)

The photoacoustic imaging contrast medium according to claim 8, further comprising an addition agent.