Ga(III) chelates of amphiphilic DOTA-based ligands: synthetic route and in vitro and in vivo studies

André Fontes; M Isabel M Prata; Carlos F G C Geraldes; João P André

doi:10.1016/j.nucmedbio.2010.10.003

Ga(III) chelates of amphiphilic DOTA-based ligands: synthetic route and in vitro and in vivo studies

Nucl Med Biol. 2011 Apr;38(3):363-70. doi: 10.1016/j.nucmedbio.2010.10.003. Epub 2010 Dec 3.

Authors

André Fontes¹, M Isabel M Prata, Carlos F G C Geraldes, João P André

Affiliation

¹ Centro de Química, Campus de Gualtar, Universidade do Minho, 4710-057 Braga, Portugal.

PMID: 21492785
DOI: 10.1016/j.nucmedbio.2010.10.003

Abstract

In this work, we report on a synthetic strategy using amphiphilic DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-based chelators bearing a variable-sized α-alkyl chain at one of the pendant acetate arms (from 6 to 14 carbon atoms), compatible with their covalent coupling to amine-bearing biomolecules. The amphiphilic behavior of the micelles-forming Ga(III) chelates (critical micellar concentration), their stability in blood serum and their lipophilicity (logP) were investigated. Biodistribution studies with the (67)Ga-labeled chelates were performed in Wistar rats, which showed a predominant liver uptake with almost no traces of the radiochelates in the body after 24 h.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chelating Agents / chemistry*
Gallium Radioisotopes / chemistry
Heterocyclic Compounds, 1-Ring / blood
Heterocyclic Compounds, 1-Ring / chemical synthesis*
Heterocyclic Compounds, 1-Ring / chemistry*
Heterocyclic Compounds, 1-Ring / pharmacokinetics
Humans
Hydrophobic and Hydrophilic Interactions*
Ligands
Male
Micelles
Rats
Rats, Wistar

Substances

Chelating Agents
Gallium Radioisotopes
Heterocyclic Compounds, 1-Ring
Ligands
Micelles
1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid