Synthesis and composition of amino acid linking groups conjugated to compounds used for the targeted imaging of tumors

Patent metadata

Field	Value
Publication number	US-9333270-B2
Application number	US-201314010098-A
Country	US
Kind code	B2
Filing date	Aug 26, 2013
Priority date	Mar 15, 2013
Publication date	May 10, 2016
Grant date	May 10, 2016

Abstract

The present disclosure relates to compounds that are useful as near-infrared fluorescence probes, wherein the compounds include i) a pteroyl ligand that binds to a target receptor protein, ii) a dye molecule, and iii) a linker molecule that comprises an amino acid or derivative thereof. The disclosure further describes methods and compositions for making and using the compounds, methods incorporating the compounds, and kits incorporating the compounds.

First claim

The invention claimed is:

1. A method of optical imaging of a biological tissue that expresses a folate receptor, the method comprising:
(a) contacting the biological tissue with a composition comprising a compound having the formula:

or a pharmaceutically acceptable salt thereof,
or isotopes thereof, wherein:
X is an single amino acid or a single amino acid derivative thereof, wherein the single amino acid or single amino acid derivative contains an —OH, —NH 2 or —SH functional group, and
Y is a dye that has a fluorescence excitation and emission spectra in the near infra red range, wherein Y is represented by the formula:

wherein, X′ is independently selected from the group consisting of O, S, N and C, and
R′ is independently selected from the group consisting of CH 2 and CH 2 CH 2 ;
and the compound maintains or enhances the fluorescence of the dye, Y;
(b) allowing time for the compound in the composition to distribute within the biological target;
(c) illuminating the tissue with an excitation light of a wavelength absorbable by the compound; and
(d) detecting the optical signal emitted by the compound.

2. The method of claim 1 , wherein the signal emitted by the compound is used to construct an image.

3. The method of claim 1 , wherein the tissue is in a subject and the subject is an animal or human.

4. The method of claim 1 , wherein in step (a) two or more fluorescent compounds whose signal properties are distinguishable are contacted with the tissue, and optionally the tissue is in a subject.

5. The method of claim 1 , wherein the illuminating and detecting steps are performed using an endoscope, catheter, tomographic system, hand-held optical imaging system, surgical goggles, or intra-operative microscope.

6. The method of claim 1 wherein the biological tissue that expresses a folate receptor has a disease that overexpresses the receptor.

7. The method of claim 6 , wherein the disease is selected from the group consisting of cancer, cardiovascular diseases, neurodegenerative diseases, immunologic diseases, autoimmune diseases, respiratory diseases, metabolic diseases, inherited diseases, infectious diseases, bone diseases, and environmental diseases.

8. The method of claim 1 wherein the amino acid is selected from the group consisting of tyrosine, cysteine, or a derivative of tyrosine or cysteine.

9. The method of claim 1 , wherein the amino acid is tyrosine.

10. The method of claim 1 wherein a carbon isotope is on the aromatic ring of tyrosine.

11. The method of claim 1 wherein a hydrogen isotope is a substituent of the aromatic ring of tyrosine.

12. The method of claim 1 wherein the amino acid derivative is a derivative of tyrosine selected from the group consisting of:

or racemic mixtures thereof.

13. The method of claim 1 wherein the amino acid includes a sulfur-containing side chain group.

14. The method of claim 13 wherein the amino acid including a sulfur-containing side chain group is cysteine.

15. The method of claim 13 wherein the amino acid including a sulfur-containing side chain group is methionine.

16. The method of claim 1 wherein the amino acid including a chalcogen-containing side chain group is selenocysteine.

Assignees

• Purdue Research Foundation

Inventors

• Low Philip S
• Kularatne Sumith A
• Mahalingam Sakkarapalayam M

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• A61K49/0034

  Indocyanine green, i.e. ICG, cardiogreen · CPC title

• G01N2021/6432

  Quenching · CPC title