MR Cholangiography Demonstrates Unsuspected Rapid Biliary Clearance of Nanoparticles in Rodents: Implications for Clinical Translation Jeff W.M. Bulte PhD, Anne H. Schmieder MS, Jochen Keupp PhD, Shelton D. Caruthers PhD, Samuel A. Wickline MD, Gregory M. Lanza MD PhD PII: DOI: Reference:
S1549-9634(14)00210-X doi: 10.1016/j.nano.2014.05.001 NANO 936
To appear in:
Nanomedicine: Nanotechnology, Biology, and Medicine
Received date: Revised date: Accepted date:
19 March 2014 2 May 2014 2 May 2014
Please cite this article as: Bulte Jeff W.M., Schmieder Anne H., Keupp Jochen, Caruthers Shelton D., Wickline Samuel A., Lanza Gregory M., MR Cholangiography Demonstrates Unsuspected Rapid Biliary Clearance of Nanoparticles in Rodents: Implications for Clinical Translation, Nanomedicine: Nanotechnology, Biology, and Medicine (2014), doi: 10.1016/j.nano.2014.05.001
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT MR Cholangiography Demonstrates Unsuspected Rapid Biliary Clearance of Nanoparticles in Rodents: Implications for Clinical
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Translation
Jeff W.M. Bulte, PhD*1, Anne H. Schmieder, MS2, Jochen Keupp, PhD3,
NU
SC
Shelton D. Caruthers, PhD2,3, Samuel A. Wickline, MD2, and Gregory M. Lanza, MD PhD2
1
Russell H. Morgan Department of Radiology and Radiological Science, Division of MR
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Research and Cellular Imaging Section, Institute for Cell Engineering, the Johns Hopkins University School of Medicine, Baltimore, MD 21205. 2Department of Medicine, Division
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of Cardiology, Washington University Medical School, St. Louis, MO 63108. 3Philips Healthcare,
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Cleveland, OH 44143. 4Philips Research, Hamburg, Germany
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Short title: Biliary Excretion of Nanoparticles in Rodents
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Correspondence: Jeff W.M. Bulte, Ph.D. The Johns Hopkins University School of Medicine Russell H. Morgan Department of Radiology and Radiological Science Division of MR Research 217 Traylor Bldg, 720 Rutland Ave Baltimore, MD 21205 Phone 443-287-0996 Fax 443-287-7945 email [email protected] W o rd c o u nt: Abstract: 100
Text: 1624
Figures: 2
References: 18
Funding: This study was supported by NIH grants CA151838 (JWMB) HL073646 (SAW), HL112518 (GL), HL113392 (GL), CA154737 (GL), CA136398, and NS073457 (GL), and DOD grant CA100623 (GL).
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ACCEPTED MANUSCRIPT Conflicts of Interest: GML and SAW are scientific co-founders of Kereos, Inc. St. Louis, MO, which sublicensed related intellectual property from Washington University Medical School.
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SDC and JK are employees of Philips Healthcare
Prior presentations or earlier publication in abstract form:
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These data were partially presented at the 6th Annual Meeting of the International Society of Magnetic Resonance in Medicine, Sydney, Australia, 1998. (Proc. of ISMRM 6th Annual
AC
CE
PT
ED
MA
NU
meeting, 209, 1998).
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ACCEPTED MANUSCRIPT Graphical abstract: MR cholangiography shows unexpected, rapid excretion of 250 nm-sized paramagnetic
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perfluorocarbon nanoparticles into the rat bile duct and small intestine in less than 5 minutes.
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ACCEPTED MANUSCRIPT Abstract Due to their small size, lower cost, short reproduction cycle, and genetic manipulation, rodents
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have been widely used to test the safety and efficacy for pharmaceutical development in human
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disease. In this report, MRI cholangiography demonstrated an unexpected rapid (95%) egg yolk phosphatidylcholine, 2 mole% phosphatidylethanolamine, and 20 mole% of the lipophilic gadolinium chelate diethylene-triamine-pentaacetic acid-bis-oleate (Gd-DTPABOA; Gateway Chemical Technologies). PFOB, glycerin, and the surfactant commixture were pre-blended with sonication and microfluidized at 14,000 PSI for 4 minutes (Microfluidics, Newton, MA, USA). PFOB particles in example 2 were produced with 20% v/v PFOB and excluded Gd-DTPA-BOA from the surfactant mixture, which was replaced with high purity (>95%) egg yolk phosphatidylcholine on an equimolar basis. Nominal particle sizes were 22080nm using dynamic light scattering (Malvern Instruments, Malvern, PA) with a
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ACCEPTED MANUSCRIPT polydispersity index
S1549-9634(14)00210-X doi: 10.1016/j.nano.2014.05.001 NANO 936
To appear in:
Nanomedicine: Nanotechnology, Biology, and Medicine
Received date: Revised date: Accepted date:
19 March 2014 2 May 2014 2 May 2014
Please cite this article as: Bulte Jeff W.M., Schmieder Anne H., Keupp Jochen, Caruthers Shelton D., Wickline Samuel A., Lanza Gregory M., MR Cholangiography Demonstrates Unsuspected Rapid Biliary Clearance of Nanoparticles in Rodents: Implications for Clinical Translation, Nanomedicine: Nanotechnology, Biology, and Medicine (2014), doi: 10.1016/j.nano.2014.05.001
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT MR Cholangiography Demonstrates Unsuspected Rapid Biliary Clearance of Nanoparticles in Rodents: Implications for Clinical
RI P
T
Translation
Jeff W.M. Bulte, PhD*1, Anne H. Schmieder, MS2, Jochen Keupp, PhD3,
NU
SC
Shelton D. Caruthers, PhD2,3, Samuel A. Wickline, MD2, and Gregory M. Lanza, MD PhD2
1
Russell H. Morgan Department of Radiology and Radiological Science, Division of MR
MA
Research and Cellular Imaging Section, Institute for Cell Engineering, the Johns Hopkins University School of Medicine, Baltimore, MD 21205. 2Department of Medicine, Division
ED
of Cardiology, Washington University Medical School, St. Louis, MO 63108. 3Philips Healthcare,
PT
Cleveland, OH 44143. 4Philips Research, Hamburg, Germany
CE
Short title: Biliary Excretion of Nanoparticles in Rodents
AC
Correspondence: Jeff W.M. Bulte, Ph.D. The Johns Hopkins University School of Medicine Russell H. Morgan Department of Radiology and Radiological Science Division of MR Research 217 Traylor Bldg, 720 Rutland Ave Baltimore, MD 21205 Phone 443-287-0996 Fax 443-287-7945 email [email protected] W o rd c o u nt: Abstract: 100
Text: 1624
Figures: 2
References: 18
Funding: This study was supported by NIH grants CA151838 (JWMB) HL073646 (SAW), HL112518 (GL), HL113392 (GL), CA154737 (GL), CA136398, and NS073457 (GL), and DOD grant CA100623 (GL).
1
ACCEPTED MANUSCRIPT Conflicts of Interest: GML and SAW are scientific co-founders of Kereos, Inc. St. Louis, MO, which sublicensed related intellectual property from Washington University Medical School.
RI P
T
SDC and JK are employees of Philips Healthcare
Prior presentations or earlier publication in abstract form:
SC
These data were partially presented at the 6th Annual Meeting of the International Society of Magnetic Resonance in Medicine, Sydney, Australia, 1998. (Proc. of ISMRM 6th Annual
AC
CE
PT
ED
MA
NU
meeting, 209, 1998).
2
ACCEPTED MANUSCRIPT Graphical abstract: MR cholangiography shows unexpected, rapid excretion of 250 nm-sized paramagnetic
AC
CE
PT
ED
MA
NU
SC
RI P
T
perfluorocarbon nanoparticles into the rat bile duct and small intestine in less than 5 minutes.
3
ACCEPTED MANUSCRIPT Abstract Due to their small size, lower cost, short reproduction cycle, and genetic manipulation, rodents
T
have been widely used to test the safety and efficacy for pharmaceutical development in human
RI P
disease. In this report, MRI cholangiography demonstrated an unexpected rapid (95%) egg yolk phosphatidylcholine, 2 mole% phosphatidylethanolamine, and 20 mole% of the lipophilic gadolinium chelate diethylene-triamine-pentaacetic acid-bis-oleate (Gd-DTPABOA; Gateway Chemical Technologies). PFOB, glycerin, and the surfactant commixture were pre-blended with sonication and microfluidized at 14,000 PSI for 4 minutes (Microfluidics, Newton, MA, USA). PFOB particles in example 2 were produced with 20% v/v PFOB and excluded Gd-DTPA-BOA from the surfactant mixture, which was replaced with high purity (>95%) egg yolk phosphatidylcholine on an equimolar basis. Nominal particle sizes were 22080nm using dynamic light scattering (Malvern Instruments, Malvern, PA) with a
5
ACCEPTED MANUSCRIPT polydispersity index
![[Biliary obstruction: MR-cholangiography with a rapid gradient-echo sequence (2D CE-Fast)].](/assets/img/hold.png)
