In Vivo and In Vitro Evaluation of Gd-DTPA-Polylysine as a Macromolecular Contrast Agent for Magnetic Resonance Imaging

Schuhmann-Giampieri, Gabriele; Schmitt‐Willich, Heribert; Frenzel, Thomas; Press, Wolf-Rüdiger; Weinmann, Hanns‐Joachim

doi:10.1097/00004424-199111000-00008

Cited by 172 publications

(118 citation statements)

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“…Gd(III) ions are highly toxic and long-term tissue retention of macromolecular MRI contrast agents may result in release of toxic Gd(III) ions due to metabolism. Various macromolecular MRI contrast agents have been prepared by conjugating the gadolinium chelates to the biodegradable macromolecules, including polyamino acids [21], polysaccharides [22] and proteins [23]. However, biodegradation of these biomedical polymers is an enzymatic process that mainly occurs in cellular lysosomal compartments.…”

Section: Polymer Gd(iii) Chelate Conjugates With a Disulfide Spacer Amentioning

confidence: 99%

Polymer platforms for drug delivery and biomedical imaging

Lü

Vaidya

2007

Journal of Controlled Release

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Biocompatible synthetic polymers have demonstrated advantageous pharmacokinetic properties as compared to small molecular agents. Incorporation of low molecular weight therapeutics and imaging agents into biocompatible polymers can optimize their pharmacokinetic properties with improved efficacy of therapy and diagnostic imaging, respectively. We have applied the concept of drug delivery to design safe and effective contrast agents for magnetic resonance imaging (MRI) and used biomedical imaging in non-invasive evaluation of drug delivery and image-guided therapy. We summarize here the recent progress in our research on biodegradable macromolecular MRI contrast agents, non-invasive visualization of in vivo drug delivery of polymeric conjugates with contrast enhanced MRI, and contrast enhanced MRI guided photodynamic therapy. The preliminary results have shown that biocompatible polymers can be used as an effective platform for drug delivery and biomedical imaging. Safe and effective imaging agents can be designed by using the concept of polymeric drug delivery. Biomedical imaging can be used as a non-invasive method for the evaluation of in vivo drug delivery of polymeric drug delivery systems. The combination of drug delivery and biomedical imaging can result in image-guided therapies, which include tumor detection, therapy and non-invasive evaluation of therapeutic responses.Biocompatible and water-soluble polymers have demonstrated unique pharmacokinetic properties, including prolonged blood circulation and tissue retention, and preferential accumulation in lesions with blood vessel hyperpermeability, because of their large sizes. Biocompatible synthetic polymers have been used as a platform for the modification of pharmacokinetics of small molecular therapeutics and imaging agents to improve their efficacy in drug delivery and molecular imaging [1,2]. The conjugation of therapeutics to biocompatible polymers prolongs in vivo drug retention time, increases drug bioavailability, reduces systemic toxicity and enhances therapeutic efficacy [3,4]. The incorporation of imaging agents into biocompatible polymers prolongs their retention in the tissues of interest with increased concentrations, which allows more accurate disease detection and characterization [5,6]. For example, the incorporation of a magnetic resonance imaging (MRI) contrast agent into a macromolecule would increase its blood circulation time for effective contrast enhanced cardiovascular imaging and tumor imaging [7,8].Both drug delivery and molecular imaging can benefit from the large sizes and unique pharmacokinetic properties of biomedical polymers. However, the applications of biomedical polymers in these areas are not mutually exclusive. In fact, the concept of drug delivery can be applied in molecular imaging to design and develop effective and specific imaging agents Correspondence to: Dr. Zheng-Rong Lu, 421 Wakara Way, Suite 318, Salt Lake City, UT 84108, Phone: 801 587-9450, Fax: 801 585-3614, Email: E-mail: zhengrong.lu@utah.edu....

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Section: Polymer Gd(iii) Chelate Conjugates With a Disulfide Spacer Amentioning

confidence: 99%

Polymer platforms for drug delivery and biomedical imaging

Lü

Vaidya

2007

Journal of Controlled Release

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“…The performance of polylysine-Gd-DTPA as an intravascular MR contrast agent was investigated with a contrast-enhanced first-pass MR technique in a closed-chest, instrumented canine model in which acute ischemia could be induced by applying a flowlimiting coronary stenosis (15). All animal experiments were performed within the guidelines established in "Position of the American Heart Association on Research Animal Use" and following the recommendations of the Panel of Euthanasia of the American Veterinary Association.…”

Section: Animal Preparation and Modelmentioning

confidence: 99%

“…Polylysine-Gd-DTPA consists of poly-L-lysine covalently linked to moieties of Gd-DTPA and is used as a macromolecular blood pool marker (15). Because of its large size and high molecular weight, the compound is distributed almost exclusively in the intravascular space.…”

Section: Contrast Agentmentioning

confidence: 99%

Regional myocardial blood volume and flow: First‐pass MR imaging with polylysine‐Gd‐DTPA

Wilke

Kroll

Merkle

et al. 1995

Magnetic Resonance Imaging

131

104

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The authors investigated the utility of an intravascular magnetic resonance (MR) contrast agent, poly-L-lysine-gadolinium diethylenetriaminepentaacetic acid (DTPA), for differentiating acutely ischemic from normally perfused myocardium with first-pass MR imaging. Hypoperfused regions, identified with microspheres, on the first-pass images displayed significantly decreased signal intensities compared with normally perfused myocardium (P < .0007). Estimates of regional myocardial blood content, obtained by measuring the ratio of areas under the signal intensityversus-time curves in tissue regions and the left ventricular chamber, averaged 0.12 mL/g ± 0.04 (n = 35), compared with a value of 0.11 mL/g ± 0.05 measured with radiolabeled albumin in the same tissue regions. To obtain MR estimates of regional myocardial blood flow, in situ calibration curves were used to transform first-pass intensity-time curves into content-time curves for analysis with a multiple-pathway, axially distributed model. Flow estimates, obtained by automated parameter optimization, averaged 1.2 mL/min/g ± 0.5 [n = 29), compared with 1.3 mL/min/g ± 0.3 obtained with tracer microspheres in the same tissue specimens at the same time. The results represent a combination of T1-weighted first-pass imaging, intravascular relaxation agents, and a spatially distributed perfusion model to obtain absolute regional myocardial blood flow and volume. Index termsContrast agent, blood pool; Contrast enhancement; Coronary vessels, diseases, 54.76; Heart, flow dynamics; Heart, MR, 51.12143; Model, mathematical; Myocardium, blood supply, 511.12143; Myocardium, MR, 511.12143 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptA growing body of evidence supports the feasibility of evaluating myocardial perfusion with magnetic resonance (MR) imaging with contrast agents. A variety of intravascular and extracellular MR contrast agents have been studied for delineation of infarcted myocardium (1-3) and for identification of acutely ischemic and reperfused cardiac muscle (4,5). The first-pass MR imaging technique with the extracellular contrast agent gadolinium diethylenetriaminepentaacetic acid (DTPA) has been used to assess myocardial perfusion in patients at rest (6,7) and during pharmacologic stress (8,9). Although experimental (10) and patient studies have demonstrated the suitability of extracellular contrast agents for detecting hypoperfused myocardium, such agents are inherently disadvantageous for flow quantification because they are not confined to a single volume compartment within the tissue. Consequently, first-pass kinetics of an extracellular agent are determined not only by blood flow but by the intravascular and interstitial distribution volumes and by permeability across the capillary wall. This exchange between the vascular and interstitial compartments greatly complicates quantification of tissue blood flow unless it is either very fast or slow compared with flow rates (11).The objective of the present study was to...

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“…[33][34][35] In the MRI technique, several complexes of gadolinium (Gd[III]) ions with high molecular weight compounds like albumin, dextran, polylysine, and dendrimers are explored. [36][37][38][39] Nanoparticles are employed in order to generate tissue-specific contrast in tumors. Gadolinium-diethylene triamine penta-acetic acid (Gd-DTPA) polylysine contrast agents are effective in the diagnosis and staging of brain and other tumors.…”

Section: Diagnostic Applicationsmentioning

confidence: 99%

Dendrimers as tunable vectors of drug delivery systems and biomedical and ocular applications

Kalomiraki¹,

Thermos²,

Chaniotakis³

2015

IJN

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Abstract:Dendrimers are large polymeric structures with nanosize dimensions (1-10 nm) and unique physicochemical properties. The major advantage of dendrimers compared with linear polymers is their spherical-shaped structure. During synthesis, the size and shape of the dendrimer can be customized and controlled, so the finished macromolecule will have a specific "architecture" and terminal groups. These characteristics will determine its suitability for drug delivery, diagnostic imaging, and as a genetic material carrier. This review will focus initially on the unique properties of dendrimers and their use in biomedical applications, as antibacterial, antitumor, and diagnostic agents. Subsequently, emphasis will be given to their use in drug delivery for ocular diseases.

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In Vivo and In Vitro Evaluation of Gd-DTPA-Polylysine as a Macromolecular Contrast Agent for Magnetic Resonance Imaging

Cited by 172 publications

References 0 publications

Polymer platforms for drug delivery and biomedical imaging

Polymer platforms for drug delivery and biomedical imaging

Regional myocardial blood volume and flow: First‐pass MR imaging with polylysine‐Gd‐DTPA

Dendrimers as tunable vectors of drug delivery systems and biomedical and ocular applications

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