| Pharmacokinetics and magnetic resonance imaging of biodegradable macromolecular blood-pool contrast agent PG-Gd in non-human primates: a pilot study. | |
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MedLine Citation:
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PMID: 21861289 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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The purpose of this study was to evaluate poly(L-glutamic acid)-benzyl-DTPA-Gd (PG-Gd), a new biodegradable macromolecular magnetic resonance imaging contrast agent, for its pharmacokinetics and MRI enhancement in nonhuman primates. Studies were performed in rhesus monkeys at intravenous doses of 0.01, 0.02 and 0.08 mmol Gd/kg. T(1) -weighted MR images were acquired at 1.5 T using fast spoiled gradient recalled echo and fast spin echo imaging protocols. The small-molecule contrast agent Magnevist was used as a control. PG-Gd in the monkey showed a bi-exponential disposition. The initial blood concentrations within 2 h of PG-Gd administration were much higher than those for Magnevist. The high blood concentration of PG-Gd was consistent with the MR imaging data, which showed prolonged circulation of PG-Gd in the blood pool. Enhancement of blood vessels and organs with a high blood perfusion (heart, liver, and kidney) was clearly visualized at 2 h after contrast injection at the three doses used. A greater than proportional increase of the area under the blood concentration-time curve was observed when the administered single dose was increased from 0.01 to 0.08 mmol/kg. By 2 days after PG-Gd injection, the contrast agent was mostly cleared from all major organs, including kidney. The mean residence time was 15 h at the 0.08 mmol/kg dose. A similar pharmacokinetic profile was observed in mice, with a mean residence time of 5.4 h and a volume of distribution at steady-state of 85.5 ml/kg, indicating that the drug was mainly distributed in the blood compartment. Based on this pilot study, further investigations on the potential systemic toxicity of PG-Gd in both rodents and large animals are warranted before testing this agent in humans. Copyright © 2011 John Wiley & Sons, Ltd. |
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Authors:
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Mei Tian; Xiaoxia Wen; Edward F Jackson; Chaan Ng; Rajesh Uthamanthil; Dong Liang; Juri G Gelovani; Chun Li |
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Publication Detail:
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Type: Journal Article Date: 2011-01-06 |
Journal Detail:
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Title: Contrast media & molecular imaging Volume: 6 ISSN: 1555-4317 ISO Abbreviation: Contrast Media Mol Imaging Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-08-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101286760 Medline TA: Contrast Media Mol Imaging Country: United States |
Other Details:
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Languages: eng Pagination: 289-97 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 John Wiley & Sons, Ltd. |
Affiliation:
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Department of Experimental Diagnostic Imaging, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. mei.tian@mdanderson.org. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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