Dataset Information

A Class of Fe^III Macrocyclic Complexes with Alcohol Donor Groups as Effective T₁ MRI Contrast Agents.

ABSTRACT: Early studies suggested that Fe^III complexes cannot compete with Gd^III complexes as T₁ MRI contrast agents. Now it is shown that one member of a class of high-spin macrocyclic Fe^III complexes produces more intense contrast in mice kidneys and liver at 30?minutes post-injection than does a commercially used Gd^III agent and also produces similar T₁ relaxivity in serum phantoms at 4.7?T and 37?°C. Comparison of four different Fe^III macrocyclic complexes elucidates the factors that contribute to relaxivity in?vivo including solution speciation. Variable-temperature ¹⁷ O NMR studies suggest that none of the complexes has a single, integral inner-sphere water that exchanges rapidly on the NMR timescale. MRI studies in mice show large in?vivo differences of three of the Fe^III complexes that correspond, in part, to their r₁ relaxivity in phantoms. Changes in overall charge of the complex modulate contrast enhancement, especially of the kidneys.

SUBMITTER: Snyder EM

PROVIDER: S-EPMC7502272 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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A Class of FeIII Macrocyclic Complexes with Alcohol Donor Groups as Effective T1 MRI Contrast Agents.

Snyder Eric M EM Asik Didar D Abozeid Samira M SM Abozeid Samira M SM Burgio Ariel A Bateman Gage G Turowski Steven G SG Spernyak Joseph A JA Morrow Janet R JR

Angewandte Chemie (International ed. in English) 20191220 6

Early studies suggested that FeIII complexes cannot compete with GdIII complexes as T1 MRI contrast agents. Now it is shown that one member of a class of high-spin macrocyclic FeIII complexes produces more intense contrast in mice kidneys and liver at 30 minutes post-injection than does a commercially used GdIII agent and also produces similar T1 relaxivity in serum phantoms at 4.7 T and 37 °C. Comparison of four different Fe ...[more]

PMID: 31725934

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Project description:In cancer diagnostics, magnetic resonance imaging (MRI) uses contrast agents to enhance the distinction between the target tissue and background. Several promising approaches have been developed to increase MRI sensitivity, one of which is Overhauser dynamic nuclear polarization (ODNP)-enhanced MRI (OMRI). In this study, a macromolecular construct based on human serum albumin and nitroxyl radicals (HSA-NIT) was developed using a new synthesis method that significantly increased the modification to 21 nitroxide residues per protein. This was confirmed by electron paramagnetic resonance (EPR) spectroscopy and matrix-assisted laser desorption/ionization time-of-flight (MALDI ToF) mass spectrometry. Gel electrophoresis and circular dichroism showed no significant changes in the structure of HSA-NITs, and no oligomers were formed during modification. The cytotoxicity of HSA-NITs was comparable to that of native albumin. HSA-NITs were evaluated as potential "metal-free" organic radical relaxation-based contrast agents for 1H-MRI and as hyperpolarizing contrast agents for OMRI. Relaxivities (longitudinal and transversal relaxation rates r1 and r2) for HSA-NITs were measured at different magnetic field strengths (1.88, 3, 7, and 14 T). Phantoms were used to demonstrate the potential use of HSA-NIT as a T1- and T2-weighted relaxation-based contrast agent at 3 T and 14 T. The efficacy of 1H Overhauser dynamic nuclear polarization (ODNP) in liquids at an ultralow magnetic field (ULF, B0 = 92 ± 0.8 μT) was investigated for HSA-NIT conjugates. The HSA-NITs themselves did not show ODNP enhancement; however, under the proteolysis conditions simulating cancer tissue, HSA-NIT conjugates were cleaved into lower-molecular-weight (MW) protein fragments that activate ODNP capabilities, resulting in a maximum achievable enhancement |Emax| of 40-50 and a radiofrequency power required to achieve half of Emax, P1/2, of 21-27 W. The HSA-NIT with a higher degree of modification released increased the number of spin probes upon biodegradation, which significantly enhanced the Overhauser effect. Thus, HSA-NITs may represent a new class of MRI relaxation-based contrast agents as well as novel cleavable conjugates for use as hyperpolarizing contrast agents (HCAs) in OMRI.

Dataset Information

A Class of Fe^III Macrocyclic Complexes with Alcohol Donor Groups as Effective T₁ MRI Contrast Agents.

Publications

A Class of Fe<sup>III</sup> Macrocyclic Complexes with Alcohol Donor Groups as Effective T<sub>1</sub> MRI Contrast Agents.

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