Targeting radiopharmaceuticals

Comparative biodistribution studies of gallium and indium complexes of multidentate ligands

Carla J. Mathias, Yizhen Sun, Michael J. Welch, Mark Green, Janice A. Thomas, Katrina R. Wade, Arthur E. Martell

Research output: Contribution to journalArticle

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Abstract

New multidentate ligands with structures similar to N,N′-bis[2-hydroxybenzyl]ethylenediamme-N,N′-diacetic acid (HBED) and N,N′-bis(pyridoxyl)ethylenediamine-N,N′-diacetic acid (PLED) were synthesized. The in vitro lipophilicity, electrophoretic behavior, and the in vivo biodistribution were studied for the 111In- and 67,68Ga-complexes of N,N′-bis(2-hydroxy-3,5-dimethylbenzyl)ethylenediamine-N,N′-diacetic acid (Me4HBED); N,N′-bis(5-t-butyl-2-hydroxy-3-methylbenzyl)ethylenediamine-N,N′-diacetic acid (t-butyl HBED); N,N′-bis[2-hydroxy-5-sulfobenzyl)ethylenediamine-N,N′-diacetic acid (SHBED); N,N′-bis(2-hydroxy-3,5-dimethylbenzyl)ethylenediamine-N-(2-hydroxyethyl)-N′-acetic acid (HBMA); and N,N′-bis(5-deoxypyridoxyl)ethylenediamine-N,N′-diacetic acid (DPLED). The biodistribution of the radiometal complexes were carried out in rats and an imaging study was performed in a non-human primate. The rapid clearance of the lipophilic complexes from blood and through the hepatobiliary system was easily demonstrated; as well, the hydrophilic complexes were cleared rapidly through the urinary tract. Positron emission tomographic images were generated from a study in a primate after administration of 68Ga-t-butyl HBED. These images well demonstrate the efficient liver accumulation and rapid hepatobiliary clearance (<1 h) and well differentiate images of the liver and gall bladder.

Original languageEnglish (US)
JournalInternational Journal of Radiation Applications and Instrumentation.
Volume15
Issue number1
DOIs
StatePublished - 1988
Externally publishedYes

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ethylenediamine
Gallium
Indium
Radiopharmaceuticals
Ligands
Acids
Primates
Liver
Urinary Tract
Acetic Acid

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Targeting radiopharmaceuticals : Comparative biodistribution studies of gallium and indium complexes of multidentate ligands. / Mathias, Carla J.; Sun, Yizhen; Welch, Michael J.; Green, Mark; Thomas, Janice A.; Wade, Katrina R.; Martell, Arthur E.

In: International Journal of Radiation Applications and Instrumentation., Vol. 15, No. 1, 1988.

Research output: Contribution to journalArticle

Mathias, Carla J. ; Sun, Yizhen ; Welch, Michael J. ; Green, Mark ; Thomas, Janice A. ; Wade, Katrina R. ; Martell, Arthur E. / Targeting radiopharmaceuticals : Comparative biodistribution studies of gallium and indium complexes of multidentate ligands. In: International Journal of Radiation Applications and Instrumentation. 1988 ; Vol. 15, No. 1.
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title = "Targeting radiopharmaceuticals: Comparative biodistribution studies of gallium and indium complexes of multidentate ligands",
abstract = "New multidentate ligands with structures similar to N,N′-bis[2-hydroxybenzyl]ethylenediamme-N,N′-diacetic acid (HBED) and N,N′-bis(pyridoxyl)ethylenediamine-N,N′-diacetic acid (PLED) were synthesized. The in vitro lipophilicity, electrophoretic behavior, and the in vivo biodistribution were studied for the 111In- and 67,68Ga-complexes of N,N′-bis(2-hydroxy-3,5-dimethylbenzyl)ethylenediamine-N,N′-diacetic acid (Me4HBED); N,N′-bis(5-t-butyl-2-hydroxy-3-methylbenzyl)ethylenediamine-N,N′-diacetic acid (t-butyl HBED); N,N′-bis[2-hydroxy-5-sulfobenzyl)ethylenediamine-N,N′-diacetic acid (SHBED); N,N′-bis(2-hydroxy-3,5-dimethylbenzyl)ethylenediamine-N-(2-hydroxyethyl)-N′-acetic acid (HBMA); and N,N′-bis(5-deoxypyridoxyl)ethylenediamine-N,N′-diacetic acid (DPLED). The biodistribution of the radiometal complexes were carried out in rats and an imaging study was performed in a non-human primate. The rapid clearance of the lipophilic complexes from blood and through the hepatobiliary system was easily demonstrated; as well, the hydrophilic complexes were cleared rapidly through the urinary tract. Positron emission tomographic images were generated from a study in a primate after administration of 68Ga-t-butyl HBED. These images well demonstrate the efficient liver accumulation and rapid hepatobiliary clearance (<1 h) and well differentiate images of the liver and gall bladder.",
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