Randall B. Lauffer
Harvard University
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Investigative Radiology | 1997
David J. Parmelee; Richard C. Walovitch; Hillori S. Ouellet; Randall B. Lauffer
RATIONALE AND OBJECTIVES The authors evaluate MS-325, a new albumin-targeted magnetic resonance imaging (MRI) contrast agent, for its pharmacokinetics, biodistribution, and elimination characteristics in multiple animal species. METHODS Studies were performed in rats, rabbits, and nonhuman primates at intravenous doses ranging from 0.025 to 0.20 mmol/kg. Concentrations of MS-325 in blood, urine, feces, and organs were determined using gadolinium-153-labeled MS-325 and gamma counting or by using non-labeled MS-325 and inductively coupled plasma atomic emission spectrometry. RESULTS In rabbits and nonhuman primates, MS-325 is approximately 85% to 95% bound to serum proteins and, as a result, exhibits low volume of distribution (Vd) values, 0.11 to 0.14 L/kg, and a long elimination half-life (Te1/2), 2 to 3 hours. Some dose-dependence in the parameters is apparent in rabbits. MS-325 is eliminated primarily through the renal system in non-human primates. In contrast, the behavior of MS-325 in rats is different, exhibiting increased biliary excretion, a larger Vd value, and a shorter Te1/2. CONCLUSIONS The pharmacokinetics and elimination profile of MS-325, including vascular retention and renal excretion, are favorable for use in humans as an intravascular contrast agent for MRI.
Magnetic Resonance Imaging | 1985
Randall B. Lauffer; Thomas J. Brady
The proteins bovine serum albumin (BSA) and bovine immunoglobulin (IgG) have been labeled with paramagnetic gadolinium (III) and manganese (II) complexes using the bifunctional chelate approach. Diethylenetriaminepentaacetic acid (DTPA) and ethylenediaminetetraacetic acid (EDTA) were attached to several free amino groups on the proteins using cyclic anhydride forms of these ligands. The incorporation of the metal ions Gd+3 and Mn+2 into the chelating groups yielded highly paramagnetic proteins. The water relaxation ability (or relaxivity) of the protein-bound chelates at 20 MHz was found to be superior to that of the free metal complexes. Differences in relaxivity between the DTPA and EDTA conjugates could largely be accounted for by differences in the metal ion exposure to water. This labeling technique can be used in the preparation of intravascular NMR contrast agents (like paramagnetically-labeled human serum albumin) or target-specific agents (labeled monoclonal antibodies or fibrinogen).
Magnetic Resonance in Medicine | 1999
Mark B. M. Hofman; Robert E. Henson; Sndor J. Kovcs; Stefan Fischer; Randall B. Lauffer; Kofi Adzamli; Jan De Becker; Samuel A. Wickline; Christine H. Lorenz
The ability of a blood pool contrast agent to enhance MR coronary angiography was defined. The proximal coronary vessels of pigs were imaged before and after administration of Gd‐DTPA bound covalently to bovine serum albumin (0.2 mmol/kg). The contrast agent resulted in a reduction of the blood T1 value to 33 ± 5 msec, as determined in vivo with a Look‐Locker technique. Both 2D and 3D imaging techniques were performed. An inversion pulse suppressed the signal of nonblood tissue postcontrast. After contrast agent administration, in the 3D data set the signal‐to‐noise ratio (SNR) of blood and contrast‐to‐noise ratio (CNR) of blood to myocardium were improved by factors of 2.0 ± 0.2 and 15 ± 8, respectively (P < 0.05). Postcontrast, the 3D acquisition was superior to the 2D technique in terms of spatial resolution, SNR of blood, and CNR of blood to myocardium. The high contrast of the 3D data set allowed for direct and rapid display of coronary arteries using a “closest vessel projection.”Magn Reson Med 41:360–367, 1999.
Journal of Computer Assisted Tomography | 1985
Randall B. Lauffer; Wl Greif; D D Stark; Alice C. Vincent; Sanjay Saini; Van J. Wedeen; Thomas J. Brady
The paramagnetic metal complex iron(III) ethylenebis-(2-hydrox-yphenylglycine) [Fe(EHPG)-] is an effective hepatobiliary contrast agent for liver enhancement in magnetic resonance (MR) imaging. The intravenous administration of 0.2 mmol/kg of Fe(EHPG)- to rats yields a 200% increase in the signal intensity of the liver when using a Tl-weighted inversion recovery pulse sequence on a 1.4 T imaging system. Biodistribution studies in rats and a rabbit, along with imaging studies in a dog at 0.6 T, confirm that the complex has significant hepatocellular uptake and appears to be excreted unaltered into the bile. Control experiments with a different iron complex. iron(III) diethyl-enetriaminepentaacetic acid, reveal little hepatic affinity and poor enhancement capability due to its extracellular distribution. This initial evaluation of Fe(EHPG)- demonstrates that paramagnetic metal complexes with hepatobiliary specificity are well suited for enhancement of normal liver parenchyma and may increase the sensitivity of MR in the detection of liver disease.
Investigative Radiology | 2002
Christoph U. Herborn; Ralph Waldschuetz; Thomas C. Lauenstein; Mathias Goyen; Randall B. Lauffer; Tarik Moeroey; Jörg F. Debatin; Stefan G. Ruehm
Herborn CU, Waldschuetz R, Lauenstein TC, et al. Contrast-enhanced magnetic resonance imaging (MS-325) in a murine model of systemic lupus erythematosus. Invest Radiol 2002;37:464–469. rationale and objectives. To investigate whether inflammatory activity can be evaluated by MRI with an intravascular compound (MS-325) in Desoxyribonuclease I (Dnase1)-deficient mice, which show classical symptoms of systemic lupus erythematosus. methods. Dnase1-deficient and normal mice (both groups n = 10) underwent MRI with a body weight adapted dose of MS-325 on a 1.5 T whole body scanner equipped with a dedicated surface coil. MR images of the kidneys and the aorta and signal to noise ratios prior and post contrast administration were compared with histopathology in all animals. results. Dnase1-knockout mice demonstrated aortic-wall enhancement and inhomogeneous-renal enhancement with significantly higher SNR values corresponding to microscopically proved inflammatory changes (P < 0.05). conclusion. MS-325-enhanced MRI appears to be a sensitive tool for the detection of renal and vascular involvement in this animal model. In addition, this method may facilitate assessment of therapeutic approaches in patients with SLE in the future.
Archive | 1983
Lawrence. Que; Randall B. Lauffer; Robert H. Heistand
Investigations into the enzyme-substrate complex of the catechol dioxygenases have vaised the possibility that the catechol may bind to the metal center in a monodentate configuration. Based on NMR studies of model monodentate and chelated catecholate complexes, the substrate is shown to be coordinated to the ferric center through only one oxygen in the catechol 1, 2-dioxygenase-4-methylcatechol complex. Rationalizations for this preferred configuration are suggested by the oxygen reactivity of various model Compounds.
Chemical Reviews | 1999
Peter Caravan; Jeffrey J. Ellison; Thomas J. McMurry; Randall B. Lauffer
Chemical Reviews | 1987
Randall B. Lauffer
Magnetic Resonance in Medicine | 1988
Arno Villringer; Bruce R. Rosen; J.W. Belliveau; Jerome L. Ackerman; Randall B. Lauffer; Richard B. Buxton; Yong-Sheng Chao; Van J. Wedeen; Thomas J. Brady
Radiology | 1998
Randall B. Lauffer; D J Parmelee; S U Dunham; H S Ouellet; R P Dolan; S Witte; T J McMurry; R C Walovitch