Tricarbonyl technetium-99m, rhenium-185/187, or rhenium-188 labeled cyclic RGD derivatives and uses thereof

A preparation method of the tricarbonyl technetium-99m or tricarbonyl rhenium-188 labeled cyclic RGD derivative selected from a group of compounds expressed by Chemical Formula 1A, 1B, and 1C comprising:

• reacting tricarbonyl technetium-99m (99mTc(CO)3(H2O)3+) or tricarbonyl rhenium-188 (188Re(CO)3(H2O)3+) with a precursor compound of Chemical Formula 2A, 2B, or 2C to prepare the tricarbonyl technetium-99m or rhenium-188 labeled cyclic RGD derivative of Chemical Formula 1A, 1B, or 1C, respectively:
• wherein,
• M is 99mTc or 188Re;
• R1 is N, N(CH2CH2O)nCH2CH2CONH or N(CH2CONH)(CH2CH2O)4CH2CH2CONH;
• n is an integer between 0 and 8;
• R3 is H or OH;
• R4 is —(CH2)m— or —(CH2)m—COO—;
• and
• m is an integer between 1 and 8,
• wherein,
• M is 99mTc or 188Re;
• R1 is N, N(CH2CH2O)nCH2CH2CONH or N(CH2CONH)(CH2CH2O)4CH2CH2CONH;
• A1 is an amino acid selected from the group consisting of aspartic acid, lysine, glutamic acid, tyrosine, cysteine, threonine, and serine;
• R2 is NH or NH(Z)nCH2CH2CONH;
• Z is —CH2CH2O— or —CH2CONH—;
• n is an integer between 0 and 8;
• R3 is H or OH;
• R4 is —(CH2)m— or —(CH2)m—COO—;
• and
• m is an integer between 1 and 8,
• and
• wherein,
• M is 99mTc or 188Re;
• R1 is N, N(CH2CH2O)nCH2CH2CONH or N(CH2CONH)(CH2CH2O)4CH2CH2CONH;
• A1 and A2 are each an amino acid selected from the group consisting of aspartic acid, lysine, glutamic acid, tyrosine, cysteine, threonine, and serine;
• R2 is NH or NH(Z)nCH2CH2CONH;
• Z is —CH2CH2O— or —CH2CONH—;
• n is an integer between 0 and 8;
• R3 is H or OH;
• R4 is —(CH2)m— or —(CH2)m—COO—;
• and
• m is an integer between 1 and 8,
• wherein R1, R3, and R4 are as defined in Chemical Formula 1A,
• wherein R1, R2, R3, R4, and A1 are as defined in Chemical Formula 1B,
• wherein R1, R2, R3, R4, A1, and A2 are as defined in Chemical Formula 1C.

A preparation method of the tricarbonyl rhenium-185/187 labeled cyclic RGD derivative comprising:

• introducing (NEt4)2185/187Re(CO)3Br3 into a precursor compound of Chemical Formula 2A, 2B, or 2C to react, thereby preparing cyclic RGD derivative of Chemical Formula 1A, 1B, or 1C, respectively:
• wherein,
• M is 185/187Re;
• R1 is N, N(CH2CH2O)nCH2CH2CONH or N(CH2CONH)(CH2CH2O)4CH2CH2CONH;
• n is an integer between 0 and 8;
• R3 is H or OH;
• R4 is —(CH2)m— or —(CH2)m—COO—;
• and
• m is an integer between 1 and 8,
• wherein,
• M is 185/187Re;
• R1 is N, N(CH2CH2O)nCH2CH2CONH or N(CH2CONH)(CH2CH2O)4CH2CH2CONH;
• A1 is an amino acid selected from the group consisting of aspartic acid, lysine, glutamic acid, tyrosine, cysteine, threonine, and serine;
• R2 is NH or NH(Z)nCH2CH2CONH;
• Z is —CH2CH2O— or —CH2CONH—;
• n is an integer between 0 and 8;
• R3 is H or OH;
• R4 is —(CH2)m— or —(CH2)m—COO—;
• and
• m is an integer between 1 and 8,
• and
• wherein,
• M is 185/187Re;
• R1 is N, N(CH2CH2O)nCH2CH2CONH or N(CH2CONH)(CH2CH2O)4CH2CH2CONH;
• A1 and A2 are each an amino acid selected from the group consisting of aspartic acid, lysine, glutamic acid, tyrosine, cysteine, threonine, and serine;
• R2 is NH or NH(Z)nCH2CH2CONH;
• Z is —CH2CH2O— or —CH2CONH—;
• n is an integer between 0 and 8;
• R3 is H or OH;
• R4 is —(CH2)m— or —(CH2)m—COO—;
• and
• m is an integer between 1 and 8,
• wherein R1, R3, and R4 are as defined in Chemical Formula 1A,
• wherein R1, R2, R3, R4, and A1 are as defined in Chemical Formula 1B,
• wherein R1, R2, R3, R4, A1, and A2 are as defined in Chemical Formula 1C.