In vivo and in vitro evaluation of Gd-DTPA-polylysine as a macromolecular contrast agent for magnetic resonance imaging
| Autor: | Thomas Frenzel, Gabriele Schuhmann-Giampieri, Heribert Schmitt-Willich, Wolf-Rüdiger Press, Hanns-Joachim Weinmann |
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| Rok vydání: | 1991 |
| Předmět: |
Gadolinium DTPA
Biodistribution Contrast Media In Vitro Techniques Lethal Dose 50 chemistry.chemical_compound Mice Pharmacokinetics Interstitial space In vivo Organometallic Compounds Animals Radiology Nuclear Medicine and imaging Polylysine Tissue Distribution Volume of distribution General Medicine Pentetic Acid Magnetic Resonance Imaging In vitro Rats chemistry Covalent bond Biophysics Female Rabbits |
| Zdroj: | Investigative radiology. 26(11) |
| ISSN: | 0020-9996 |
| Popis: | Polylysine covalently linked to moieties of gadopentetate (Gd-DTPA), for use as a macromolecular blood pool marker for contrast material-enhanced magnetic resonance imaging (MRI), was characterized by means of physicochemical measurements and pharmacokinetics in rats and rabbits and compared with Gd-DTPA. Gd-DTPA-polylysine was composed of a series of polymers of different molecular sizes that on average were labeled with 60 to 70 Gd-DTPA moieties (average molecular weight, 48,700 daltons [D]). For the macromolecular compound Gd-DTPA-polylysine, relaxivity was three times higher than that of Gd-DTPA. The LD50 value of 17 mmol/kg reflects a fairly high acute intravenous tolerance of the macromolecular compound in mice. Even though the volume of distribution of Gd-DTPA-polylysine in rabbits approached the extracellular fluid space (indicating that the macromolecular compound was also leaking slowly into the interstitial space), the half-life of distribution of the macromolecular compound in the extracellular fluid space was significantly prolonged, thus making the compound suitable as a blood pool marker for MRI. In rats the elimination of Gd-DTPA-polylysine occurred predominantly via the renal route. High-pressure liquid chromatography-size-exclusion chromatography of the fractionated urine samples revealed that the renal clearance must be the integral sum of the separate clearances of each molecular weight species. No biodegradation of the polypeptide was observed, and biodistribution studies revealed only minimal retention of Gd in the body of the rat. |
| Databáze: | OpenAIRE |
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