Gd complexes of DO3A-(biphenyl-2,2′-bisamides) conjugates as MRI blood-pool contrast agents

Ki Hye Jung; Hee Kyung Kim; Ji Ae Park; Ki Soo Nam; Gang Ho Lee; Yongmin Chang; Tae Jeong Kim

doi:10.1021/ml300223b

Gd complexes of DO3A-(biphenyl-2,2′-bisamides) conjugates as MRI blood-pool contrast agents

Ki Hye Jung, Hee Kyung Kim, Ji Ae Park, Ki Soo Nam, Gang Ho Lee, Yongmin Chang, Tae Jeong Kim

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

We report the synthesis of DO3A derivatives of 2,2′-diaminobiphenyl (1a,b) and their Gd complexes of the type [Gd(1)(H₂O)]·xH ₂O (2a,b) for use as new MRI blood-pool contrast agents (BPCAs) that provide strong and prolonged vascular enhancement. Pharmacokinetic inertness of 2 compares well with that of structurally related Dotarem, a DOTA-based MRI CA currently in use. The R₁ relaxivity in water reaches 7.3 mM ^-1 s^-1, which is approximately twice as high as that of Dotarem (R₁ = 3.9 mM^-1 s^-1). They show interaction with HSA to give association constants (K_a) in the order of two (∼10²), revealing the existence of the blood-pool effect. The in vivo MR images of mice obtained with 2 are coherent, showing strong signal enhancement in both heart, abdominal aorta, and small vessels. Furthermore, the brain tumor is vividly enhanced for an extended period of time.

Original language	English
Pages (from-to)	1003-1007
Number of pages	5
Journal	ACS Medicinal Chemistry Letters
Volume	3
Issue number	12
DOIs	https://doi.org/10.1021/ml300223b
State	Published - 13 Dec 2012

Keywords

DO3A
Gd chelates
MRI BPCA
biphenyl
brain tumor

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title = "Gd complexes of DO3A-(biphenyl-2,2′-bisamides) conjugates as MRI blood-pool contrast agents",

abstract = "We report the synthesis of DO3A derivatives of 2,2′-diaminobiphenyl (1a,b) and their Gd complexes of the type [Gd(1)(H2O)]·xH 2O (2a,b) for use as new MRI blood-pool contrast agents (BPCAs) that provide strong and prolonged vascular enhancement. Pharmacokinetic inertness of 2 compares well with that of structurally related Dotarem, a DOTA-based MRI CA currently in use. The R1 relaxivity in water reaches 7.3 mM -1 s-1, which is approximately twice as high as that of Dotarem (R1 = 3.9 mM-1 s-1). They show interaction with HSA to give association constants (Ka) in the order of two (∼102), revealing the existence of the blood-pool effect. The in vivo MR images of mice obtained with 2 are coherent, showing strong signal enhancement in both heart, abdominal aorta, and small vessels. Furthermore, the brain tumor is vividly enhanced for an extended period of time.",

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author = "Jung, {Ki Hye} and Kim, {Hee Kyung} and Park, {Ji Ae} and Nam, {Ki Soo} and Lee, {Gang Ho} and Yongmin Chang and Kim, {Tae Jeong}",

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doi = "10.1021/ml300223b",

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AU - Jung, Ki Hye

AU - Kim, Hee Kyung

AU - Park, Ji Ae

AU - Nam, Ki Soo

AU - Lee, Gang Ho

AU - Chang, Yongmin

AU - Kim, Tae Jeong

PY - 2012/12/13

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N2 - We report the synthesis of DO3A derivatives of 2,2′-diaminobiphenyl (1a,b) and their Gd complexes of the type [Gd(1)(H2O)]·xH 2O (2a,b) for use as new MRI blood-pool contrast agents (BPCAs) that provide strong and prolonged vascular enhancement. Pharmacokinetic inertness of 2 compares well with that of structurally related Dotarem, a DOTA-based MRI CA currently in use. The R1 relaxivity in water reaches 7.3 mM -1 s-1, which is approximately twice as high as that of Dotarem (R1 = 3.9 mM-1 s-1). They show interaction with HSA to give association constants (Ka) in the order of two (∼102), revealing the existence of the blood-pool effect. The in vivo MR images of mice obtained with 2 are coherent, showing strong signal enhancement in both heart, abdominal aorta, and small vessels. Furthermore, the brain tumor is vividly enhanced for an extended period of time.

AB - We report the synthesis of DO3A derivatives of 2,2′-diaminobiphenyl (1a,b) and their Gd complexes of the type [Gd(1)(H2O)]·xH 2O (2a,b) for use as new MRI blood-pool contrast agents (BPCAs) that provide strong and prolonged vascular enhancement. Pharmacokinetic inertness of 2 compares well with that of structurally related Dotarem, a DOTA-based MRI CA currently in use. The R1 relaxivity in water reaches 7.3 mM -1 s-1, which is approximately twice as high as that of Dotarem (R1 = 3.9 mM-1 s-1). They show interaction with HSA to give association constants (Ka) in the order of two (∼102), revealing the existence of the blood-pool effect. The in vivo MR images of mice obtained with 2 are coherent, showing strong signal enhancement in both heart, abdominal aorta, and small vessels. Furthermore, the brain tumor is vividly enhanced for an extended period of time.

KW - DO3A

KW - Gd chelates

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KW - biphenyl

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ER -

Gd complexes of DO3A-(biphenyl-2,2′-bisamides) conjugates as MRI blood-pool contrast agents

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