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Article

A Second Generation Mn-Porphyrin Dimer with a Twisted Linker as a Potential Blood Pool Agent for MRI: Tuning the Geometry and Binding with HSA

by 1,2,†, 1,2,†, 2, 2, 1,2 and 1,2,3,*
1
Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON M5S 3H6, Canada
2
Department of Physical and Environmental Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada
3
Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceuticals 2020, 13(10), 282; https://doi.org/10.3390/ph13100282
Received: 24 August 2020 / Revised: 25 September 2020 / Accepted: 27 September 2020 / Published: 29 September 2020
(This article belongs to the Special Issue Next Generation of MRI Agents)
Blood-pool agents (BPAs) are MRI contrast agents (CAs) characterized by their long circulation in the vascular system to provide an extended time window for high-resolution MR angiography (MRA). Prolonged vascular retention, however, impedes the excretion of BPAs. Therefore, chemical strategy to regulate the balance between retention and clearance is important to reach optimal pharmacokinetics. We recently developed MnP2, the first Mn(III)-porphyrin (MnP) based BPA. MnP2 shows high T1 relaxivity (r1) and high affinity to human serum albumin (HSA) that leads to up to 48-h vascular retention in rats. However, upon albumin binding, the r1 is decreased. To modulate vascular retention time and plasma r1, a regioisomer of MnP2, m-MnP2, was synthesized. The free m-MnP2 exhibits lower r1 than that of MnP2 at magnetic fields above 2 MHz, which agrees with their relative hydrodynamic sizes. The HSA binding of m-MnP2 was evaluated using UV-Vis spectroscopy and found to have tuned-down affinity in comparison with MnP2. Upon HSA binding, the protein complex of m-MnP2 exhibits an r1 of 11.8 mM−1 s−1 at 3 T, which is higher than that of MnP2 bound to HSA. Taken together, this demonstrated the role of molecular geometry in optimizing the pharmacokinetics of albumin-targeting BPAs. View Full-Text
Keywords: MRI contrast agents; blood pool agent; manganese porphyrin; human serum albumin MRI contrast agents; blood pool agent; manganese porphyrin; human serum albumin
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MDPI and ACS Style

Liu, H.; Cheng, W.; Dong, S.; Xu, D.F.; Tang, K.; Zhang, X.-a. A Second Generation Mn-Porphyrin Dimer with a Twisted Linker as a Potential Blood Pool Agent for MRI: Tuning the Geometry and Binding with HSA. Pharmaceuticals 2020, 13, 282. https://doi.org/10.3390/ph13100282

AMA Style

Liu H, Cheng W, Dong S, Xu DF, Tang K, Zhang X-a. A Second Generation Mn-Porphyrin Dimer with a Twisted Linker as a Potential Blood Pool Agent for MRI: Tuning the Geometry and Binding with HSA. Pharmaceuticals. 2020; 13(10):282. https://doi.org/10.3390/ph13100282

Chicago/Turabian Style

Liu, Hanlin, Weiran Cheng, Shili Dong, David F. Xu, Keith Tang, and Xiao-an Zhang. 2020. "A Second Generation Mn-Porphyrin Dimer with a Twisted Linker as a Potential Blood Pool Agent for MRI: Tuning the Geometry and Binding with HSA" Pharmaceuticals 13, no. 10: 282. https://doi.org/10.3390/ph13100282

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