Pharmacokinetics of Chiral Dendrimer-Triamine-Coordinated Gd-MRI Contrast Agents Evaluated by in Vivo MRI and Estimated by in Vitro QCM

Recently, we developed novel chiral dendrimer-triamine-coordinated Gd-MRI contrast agents (Gd-MRI CAs), which showed longitudinal relaxivity (r1) values about four times higher than that of clinically used Gd-DTPA (Magnevist®, Bayer). In our continuing study of pharmacokinetic differences derived from both the chirality and generation of Gd-MRI CAs, we found that the ability of chiral dendrimer Gd-MRI CAs to circulate within the body can be directly evaluated by in vitro MRI (7 T). In this study, the association constants (Ka) of chiral dendrimer Gd-MRI CAs to bovine serum albumin (BSA), measured and calculated with a quartz crystal microbalance (QCM) in vitro, were found to be an extremely easy means for evaluating the body-circulation ability of chiral dendrimer Gd-MRI CAs. The Ka values of S-isomeric dendrimer Gd-MRI CAs were generally greater than those of R-isomeric dendrimer Gd-MRI CAs, which is consistent with the results of our previous MRI study in vivo.

[1]  M. Yaffe,et al.  American Cancer Society Guidelines for Breast Screening with MRI as an Adjunct to Mammography , 2007, CA: a cancer journal for clinicians.

[2]  Peter Caravan,et al.  MR imaging probes: design and applications. , 2015, Dalton transactions.

[3]  R R Edelman,et al.  Magnetic resonance imaging (1). , 1993, The New England journal of medicine.

[4]  É. Boisselier,et al.  Dendrimers designed for functions: from physical, photophysical, and supramolecular properties to applications in sensing, catalysis, molecular electronics, photonics, and nanomedicine. , 2010, Chemical reviews.

[5]  Thommey P. Thomas,et al.  Nanoparticle targeting of anticancer drug improves therapeutic response in animal model of human epithelial cancer. , 2005, Cancer research.

[6]  E. W. Meijer,et al.  Dendrimers and magnetic resonance imaging , 2007 .

[7]  R. Lauffer,et al.  Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications. , 1999, Chemical reviews.

[8]  Ambika Bumb,et al.  Macromolecules, dendrimers, and nanomaterials in magnetic resonance imaging: the interplay between size, function, and pharmacokinetics. , 2010, Chemical reviews.

[9]  P C Lauterbur,et al.  Dendrimer‐based metal chelates: A new class of magnetic resonance imaging contrast agents , 1994, Magnetic resonance in medicine.

[10]  Nicholas J Long,et al.  Lanthanides in magnetic resonance imaging. , 2006, Chemical Society reviews.

[11]  A. Weller,et al.  Gadolinium and nephrogenic systemic fibrosis: an update , 2014, Pediatric Nephrology.

[12]  Karl Wieghardt,et al.  The Chemistry of 1,4,7‐Triazacyclononane and Related Tridentate Macrocyclic Compounds , 2007 .

[13]  Martin W. Brechbiel,et al.  MOLECULAR DYNAMICS OF ION-CHELATE COMPLEXES ATTACHED TO DENDRIMERS , 1996 .

[14]  G. Sauerbrey.  Verwendung von Schwingquarzen zur Wägung dünner Schichten und zur Mikrowägung , 1959 .

[15]  Martin W. Brechbiel,et al.  Macromolecular and dendrimer-based magnetic resonance contrast agents , 2010, Acta radiologica.

[16]  H. Abujudeh,et al.  Current status of nephrogenic systemic fibrosis. , 2014, Clinical radiology.

[17]  Walter H. Backes,et al.  Multivalent Contrast Agents Based on Gadolinium-Diethylenetriaminepentaacetic Acid-Terminated Poly(propylene imine) Dendrimers for Magnetic Resonance Imaging , 2004 .

[18]  K. Raymond,et al.  High-relaxivity MRI contrast agents: where coordination chemistry meets medical imaging. , 2008, Angewandte Chemie.

[19]  Gary H. Glover,et al.  Foundations of advanced magnetic resonance imaging , 2005, NeuroRX.

[20]  Teruyuki Kondo,et al.  Synthesis and functional evaluation of chiral dendrimer–triamine-coordinated Gd complexes as highly sensitive MRI contrast agents , 2012 .

[21]  R. Edelman,et al.  Magnetic resonance imaging (2) , 1993, The New England journal of medicine.

[22]  G. Sauerbrey,et al.  Use of quartz vibration for weighing thin films on a microbalance , 1959 .

[23]  M. Perazella,et al.  How should nephrologists approach gadolinium-based contrast imaging in patients with kidney disease? , 2008, Clinical journal of the American Society of Nephrology : CJASN.

[24]  J A Frank,et al.  Synthesis and relaxometry of high‐generation (G = 5, 7, 9, and 10) PAMAM dendrimer‐DOTA‐gadolinium chelates , 1999, Journal of magnetic resonance imaging : JMRI.

[25]  Baris Turkbey,et al.  Dendrimer-based MRI contrast agents: the effects of PEGylation on relaxivity and pharmacokinetics. , 2011, Nanomedicine : nanotechnology, biology, and medicine.

[26]  C. Fee,et al.  Label-free, real-time interaction and adsorption analysis 2: quartz crystal microbalance. , 2013, Methods in molecular biology.

[27]  Hisataka Kobayashi,et al.  Activated clearance of a biotinylated macromolecular MRI contrast agent from the blood pool using an avidin chase. , 2003, Bioconjugate chemistry.

[28]  Teruyuki Kondo,et al.  Synthesis and functional evaluation of chiral dendrimer-triamine-coordinated Gd complexes with polyaminoalcohol end groups as highly sensitive MRI contrast agents , 2015 .

[29]  Peter Caravan,et al.  Contrast agents for MRI: 30+ years and where are we going? , 2014, JBIC Journal of Biological Inorganic Chemistry.

[30]  P. Hermann,et al.  Gadolinium(III) complexes as MRI contrast agents: ligand design and properties of the complexes. , 2008, Dalton transactions.

[31]  Hisataka Kobayashi,et al.  Nano-sized MRI contrast agents with dendrimer cores. , 2005, Advanced drug delivery reviews.

[32]  Magdalena Labieniec,et al.  PAMAM dendrimers — diverse biomedical applications. Facts and unresolved questions , 2009, Central European Journal of Biology.

[33]  M. Perazella,et al.  Gadolinium-contrast toxicity in patients with kidney disease: nephrotoxicity and nephrogenic systemic fibrosis. , 2008, Current drug safety.

[34]  M. Perazella,et al.  Current status of gadolinium toxicity in patients with kidney disease. , 2009, Clinical journal of the American Society of Nephrology : CJASN.