Diagnostic imaging contrast agents with extended blood retention

A diagnostic imaging contrast agent comprising the following formula:

• IEM−[(L)m−{(BHEM)s−(PPBM)o}p]q
• wherein IEM is an image-enhancing moiety,
• L is a linker moiety,
• BHEM is a blood half-life extending moiety possessing two or more electropositive hydrogen atoms, or two or more lone electron pairs that cannot be partially or fully neutralized by covalent or coordinate covalent bonding to the IEM, and is selected from the group consisting of sulfone, urea, thio-urea, amine, sulfonamide, carbamate, peptide, ester, carbonate, acetals and
• 26
• or ester forms,
• where
• Z=P, W, Mo, or S
• Y1, Y2=O or S
• Y3, Y4=O, S or not present
• R2=H, C1-6 alkyl or not present,
• PPBM is a plasma protein binding moiety comprising at least seven carbon atoms,
• m can be equal to 0-4,
• s, o, and p can be the same or different and equal to 1-4,
• and q is at least one.

A diagnostic imaging contrast agent comprising the following formula:

• 28
• wherein IEM is an image-enhancing moiety,
• BHEM is a blood half-life extending moiety possessing two or more electropositive hydrogen atoms, or two or more lone electron pairs that cannot be partially or fully neutralized by covalent or coordinate covalent bonding to the IEM, and is selected from the group consisting of sulfone, urea, thio-urea, amine, sulfonamide, carbamate, peptide, ester, carbonate, acetals and
• 29
• or ester forms,
• where
• Z=P, W, or Mo
• Y1, Y2=O or S
• Y3, Y4=O S or not present
• R2=H, C1-6 alkyl or not present,
• PPBM is a plasma protein binding moiety comprising at least seven carbon atoms,
• s and o can be the same or different and equal to 1-4,
• and r is at least one.

A diagnostic imaging contrast agent comprising the following formula:

• 31
• wherein IEM is an image-enhancing moiety,
• L is a linker moiety,
• BHEM is a blood half-life extending moiety possessing two or more electropositive hydrogen atoms, or two or more lone electron pairs that cannot be partially or fully neutralized by covalent or coordinate covalent bonding to the IEM, and is selected from the group consisting of sulfone, urea, thio-urea, amine, sulfonamide, carbamate, peptide, ester, carbonate, acetals, SO3− or ester forms and
• 32
• or ester forms,
• where
• Z=P, W, Mo, or S
• Y1, Y2=O or S
• Y3, Y4=O, S or not present
• R2=H, C1-6 alkyl or not present,
• PPBM is a plasma protein binding moiety comprising at least seven carbon atoms,
• m can be equal to 0-4,
• s and o can be the same or different and equal to 1-4.

A diagnostic imaging contrast agent comprising:

• 34
• wherein M is a metal ion with an atomic number of 21-29, 42, 44 or 57-83,
• R1-R11 and R16 can be the same or different and selected from the group consisting of H, PPBM, BHEM and C1-6 alkyl,
• provided that at least one of R1-R11 or R16 is PPBM,
• also provided that at least one of R1-R11 or R16 is BHEM,
• R12, R13 and R14 can be the same or different and selected from the group consisting of O− and N(H) R17,
• R15=H, CH2CH(OH)CH3, hydroxy alkyl or CH(R16) COR12,
• R17=H or C1-6 alkyl,
• BHEM is a blood half-life extending moiety possessing two or more electropositive hydrogen atoms, or two or more lone electron pairs that cannot be partially or fully neutralized by covalent or coordinate covalent bonding to the IEM, and is selected from the group consisting of sulfone, urea, thio-urea, amine, sulfonamide, carbamate, peptide, ester, carbonate, acetals, COO— or ester forms, SO3− or ester forms and
• 35
• or ester forms,
• where
• Z=P, W, Mo, or S
• Y1, Y2=O or S
• Y3, Y4=O, S or not present
• R2=H, C1-6 alkyl or not present,
• PPBM is a plasma protein binding moiety comprising at least seven carbon atoms.