Positron emission tomography radiotracer for diseases associated with translocator protein overexpression, translocator protein-targeting ligand for fluorescence imaging-guided surgery and photodynamic therapy, and production methods therefor

A method for producing a fluorine-18-labeled positron emission tomography (PET) radiotracer for targeting translocator protein overexpression, the method comprising the steps of:

• preparing a solvent-evaporated fluorine-18 reaction solution by adding water having fluorine-18 dissolved therein to acetonitrile, followed by heating to a temperature of 85 to 95° C.;
• producing a boron ester precursor by reacting a 2-aryl-6,8-dichloroimidazopyridine derivative with bis(pinacolato)diboron;
• preparing a boron ester precursor reaction solution by dissolving the boron ester precursor and a copper catalyst (copper(II) trifluoromethanesulfonate, or tetrakis(pyridine)copper(II) triflate) in dimethylformamide (DMF);
• and
• producing a radiotracer composition containing a fluorine-18-labeled radiotracer compound by adding the boron ester precursor reaction solution to the fluorine-18 reaction solution, followed by heating and reaction.

A fluorine-18-labeled positron emission tomography (PET) radiotracer for targeting translocator protein overexpression, which is represented by Formula 1 below and produced by a method comprising the steps of:

• preparing a solvent-evaporated fluorine-18 reaction solution by adding water having fluorine-18 dissolved therein to acetonitrile, followed by heating to a temperature of 85 to 95° C.;
• producing an iodonium salt precursor by reacting a 2-aryl-6,8-dichloroimidazopyridine derivative with a (diacetoxy)iodoarene derivative;
• preparing an iodonium salt precursor reaction solution by dissolving the iodonium salt precursor and 2,2,6,6-tetramethyl-1-piperidinyloxyl in acetonitrile;
• and
• producing a radiotracer composition containing a fluorine-18-labeled radiotracer compound by adding the iodonium salt precursor reaction solution to the fluorine-18 reaction solution, followed by heating and reaction:
• wherein R is 18F or 19F, X is C or N, and Y is C or N.

A fluorine-18-labeled positron emission tomography (PET) radiotracer for targeting translocator protein overexpression, which is represented by Formula 1 below and produced by a method comprising the steps of:

• preparing a solvent-evaporated fluorine-18 reaction solution by adding water having fluorine-18 dissolved therein to acetonitrile, followed by heating to a temperature of 85 to 95° C.;
• producing a boron ester precursor by reacting a 2-aryl-6,8-dichloroimidazopyridine derivative with bis(pinacolato)diboron;
• preparing a boron ester precursor reaction solution by dissolving the boron ester precursor and a copper catalyst (copper(II) trifluoromethanesulfonate, or tetrakis(pyridine)copper(II) triflate) in dimethylformamide (DMF);
• and
• producing a radiotracer composition containing a fluorine-18-labeled radiotracer compound by adding the boron ester precursor reaction solution to the fluorine-18 reaction solution, followed by heating and reaction:
• wherein R is 18F or 19F, X is C or N, and Y is C or N.

A fluorescent dye-labeled or sensitizer-labeled, translocator protein overexpression-targeting ligand tracer for fluorescence imaging-guided surgery and photodynamic therapy, which is represented by Formula 3 below and produced by a method comprising the step of producing a sensitizer-labeled ligand as a fluorescent ligand by reacting a precursor of a 2-aryl-6,8-dichloroimidazopyridine derivative with a fluorescent dye or a photodynamic therapy sensitizer, which has a functional group for complementary bonding to the precursor:

• wherein X is C or N;
• Y is C or N;
• the number (n) of polyethylene glycol (PEG) chains is 1 to 10;
• the linker that connects the PEG to the fluorescent dye or the photodynamic therapy sensitizer is a compound selected from the group consisting of ether, amide, ester, urea, urethane, thiourea, and disulfide;
• and the PEG is substituted at any one of the 2-, 3- or 4-positions of the ring containing X and Y.