Method for labeling of sensitive and thermosensitive targeting biomolecules with technetium based compounds

A compound of formula (I)

• wherein:
• Tc is 99mTc;
• R is hydrogen (—H) or a group of formula —(CH2)n-A, wherein n is an integer of 1 or 2 and A is selected from the group consisting of hydrogen (—H), hydroxyl (—OH), methyl (—CH3), carboxyl (—COOH), sodium carbonyl (—COONa), amino (—NH2), cyanide (—CN), sulfonyl (—SO3H) and sodium sulfonyl (—SO3Na);
• R1 is a group of formula —(CH2)m—R2, wherein m is an integer of 1 to 6 and R2 is selected from the group consisting of alkoxyl (—O-Ak), hydroxyl (—OH), carboxyl (—COOH), and amino (—NH2);
• and
• ZY is a bidentate ligand, coordinated with Tc through a combination of electron-donating atoms selected from the group consisting of [O−,S−], [S−,S−], [O−,S], [O,S−], [N,S−], [N−,S], and [N−,S−];
• or a salt thereof.

A process for preparation of a compound of formula (I)

• wherein:
• Tc is 99mTc;
• R is hydrogen (—H) or a group of formula —(CH2)n-A, wherein n is an integer of 1 or 2 and A is selected from the group consisting of hydrogen (—H), hydroxyl (—OH), methyl (—CH3), carboxyl (—COOH), sodium carboxyl (—COONa), amino (—NH2), cyanide (—CN), sulfonyl (—SO3H) and sodium sulfonyl (—SO3Na);
• R1 is a group of formula —(CH2)m—R2, wherein m is an integer of 1 to 6 and R2 is selected from the group consisting of alkoxyl (—O-Ak), hydroxyl (—OH), carboxyl (—COOH), and amino (—NH2);
• and
• ZY is a bidentate ligand, coordinated with Tc through a combination of electron-donating atoms selected from the group consisting of [O−,S−], [S−,S−], [O−,S], [O,S−], [N,S−], [N−,S], and [N−,S−], wherein ZY is not coordinated with Tc through [N,S−] if R is —CH3 and R1 is —(CH2)2—OCH3, comprising:
• reacting, at mild temperature and mild pH, 99mTc-pertechnetate, a reducing agent, a nitrido nitrogen donor, and ZY with a bisphosphinoamine compound of formula (VII)
• or formula (VIII)