Radioactive probe for detecting hydrogen sulfide

Abstract

Provided is a probe for detecting in vivo hydrogen sulfide, specifically, a probe for detecting hydrogen sulfide including a complex compound into which a radioactive isotope Cu is introduced. According to specific embodiments of the present disclosure, as a result of real-time observing animal models, in which hydrogen sulfide involved in various diseases is generated in a large quantity, through optical and nuclear medicine imaging, the probe for detecting hydrogen sulfide according to the present disclosure may selectively bind with hydrogen sulfide to provide images of a site where hydrogen sulfide has abnormally increased in a cell or a tissue, thereby detecting a disease in an unexpected site without affecting the anatomical properties of the body. Accordingly, the probe may be effectively used as a means for diagnosing diseases, such as a composition for imaging, an imaging method, etc.

What is claimed is: 
     
         1 . A method of measuring, detecting or imaging hydrogen sulfide in a cell or a tissue comprising administering the probe for detecting hydrogen sulfide comprising the radioactive isotope Cu-introduced complex compound which is represented by the following Chemical Formula 1; and performing the measuring, the detecting, or the imaging the hydrogen sulfide in the cell or the tissue: 
       
         
           
           
               
               
           
         
         (wherein X 1 , X 2  and X 3  are each independently one or more selected from N, O, and S; 
         Y 1  and Y 2  are each independently C or N; 
         A and B are each independently one or more selected from no bond, C(R 9 ) (R 10 )—C(R 11 )(R 12 )—, —C(R 9 )—C(R 10 )(R 11 )—C(R 12 )(R 13 )—, and C(R 9 )(R 10 )—C(R 11 )(R 12 )—C(R 13 )(R 14 )—, and ═C(R 9 )—C(R 10 )—; 
         R 1  to R 14  are each independently one or more selected from no bond, hydrogen, hydroxy, substituted or unsubstituted C 1 -C 6  linear or branched alkyl, substituted or unsubstituted C 1 -C 6  linear or branched alkyloxycarbonyl, substituted or unsubstituted C 5 -C 12  aryl C 1 -C 6  alkyl, substituted or unsubstituted C 5 -C 12  heterocycloalkyl, substituted or unsubstituted C 5 -C 20  aryl, substituted or unsubstituted C 5 -C 20  arylsulfonyl, C 1 -C 6  alkylamine, C 1 -C 6  dialkylamine, and substituted or unsubstituted amine, 
         the ‘substituted’ means being substituted with one or more substituents selected from hydroxy, hydroxy C 1 -C 6  alkyl, C 1 -C 6  dialkylamine, nitro, and  64 Cu-labeled 3-methyl-1,4,7,10-tetraazacyclotridecane, 
         R 5  and R 8  or R 6  and R 7  bind to each other to form a C 4 -C 8  cycloalkyl ring; 
         - - - is a single bond or a double bond, 
         Cu is any one selected from  60 Cu,  61 Cu,  62 Cu,  64 Cu, and  67 Cu). 
       
     
     
         2 . The method of measuring, detecting or imaging hydrogen sulfide in a cell or a tissue of  claim 1 , wherein the imaging of hydrogen sulfide is performed by measuring Cherenkov radiation emitted from the radioactive isotope Cu. 
     
     
         3 . The method of measuring, detecting or imaging hydrogen sulfide in a cell of  claim 2 , wherein Cherenkov radiation has a wavelength of 200 nm to 1000 nm. 
     
     
         4 . The method of measuring, detecting or imaging hydrogen sulfide in a cell or a tissue of  claim 1 , wherein the probe for detecting hydrogen sulfide comprising the radioactive isotope Cu-introduced complex compound images hydrogen sulfide in a site where hydrogen sulfide is abnormally increased or in a cell or extracellular matrix localized to the site, after being administered. 
     
     
         5 . The method of measuring, detecting or imaging hydrogen sulfide in a cell or a tissue of  claim 1 , wherein the complex compound reacts with the hydrogen sulfide to form a copper sulfide. 
     
     
         6 . The method of measuring, detecting or imaging hydrogen sulfide in a cell or a tissue of  claim 1 , wherein the complex compound is any one selected from 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         7 . The method of measuring, detecting or imaging hydrogen sulfide in a cell or a tissue of  claim 1 , wherein the probe is comprising the complex compound in a dose of 50 μCi/kg-1000 μCi/kg, based on a dose immediately before use. 
     
     
         8 . The method of measuring, detecting or imaging hydrogen sulfide in a cell or a tissue of  claim 1 , wherein the complex compound is used in one or more selected from a contrast agent for positron emission tomography (PET), a contrast agent for gamma camera, single photon emission computed tomography (SPECT), or Cherenkov optical imaging, a contrast agent for charge-coupled device (CCD), a contrast agent for magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound (US). 
     
     
         9 . A method for diagnosing diseases associated with hydrogen sulfide, comprising administering the probe for detecting hydrogen sulfide comprising the radioactive isotope Cu-introduced complex compound of  claim 1  to a subject in need thereof; and performing measuring, detecting, or imaging hydrogen sulfide in a cell or a tissue of the subject. 
     
     
         10 . The method of  claim 9 , wherein the diseases are one or more selected from inflammatory diseases, cardiac diseases, Parkinson's disease, Alzheimer's disease, Down syndrome, tumors, sepsis, pains, arteriosclerosis, diabetes, stroke, liver cirrhosis, and asthma. 
     
     
         11 . The method of  claim 10 , wherein the inflammatory diseases are one or more selected from rheumatoid arthritis, non-rheumatoid inflammatory arthritis, Lyme disease-associated arthritis, inflammatory osteoarthritis, encephalomeningitis, osteomyelitis, inflammatory bowel disease, appendicitis, pancreatitis, sepsis, pyelitis, nephritis, and inflammatory diseases caused by bacterial infections. 
     
     
         12 . The method of  claim 10 , wherein the cardiac diseases are one or more selected from myocardial infarction, cardiac ischemia, angina, cardiomyopathy, and endocarditis. 
     
     
         13 . The method of  claim 10 , wherein the diagnosing of tumors is to diagnose hypoxia in tumors.