Journal article
Isomeric Trimethylene and Ethylene Pendant-armed Cross-bridged Tetraazamacrocycles and in Vitro/in Vivo Comparisions of their Copper(II) Complexes
Inorganic chemistry, Vol.50(7), pp.3078-3086
04/04/2011
DOI: 10.1021/ic200014w
PMCID: PMC3065210
PMID: 21381676
Abstract
Ethylene cross-bridged tetraamine macrocycles are useful chelators in coordination, catalytic, medicinal, and radiopharmaceutical chemistry. Springborg and co-workers developed trimethylene cross-bridged analogues, although their pendant-armed derivatives received little attention. We report here the synthesis of a bis-carboxymethyl pendant-armed cyclen with a trirnethylene cross-bridge (C3B-DO2A) and its isomeric ethylene-cross-bridged homocyclen ligand (CB-TR2A) as well as their copper(II) complexes. The in vitro and in vivo properties of these complexes are compared with respect to their potential application as Cu-64-radiopharmaceuticals in positron emission tomography (PET imaging). The inertness of Cu-C3B-DO2A to decomplexation is remarkable, exceeding that of Cu-CB-TE2A. Electrochemical reduction of Cu-CB-TR2A is quasi-reversible, whereas that of Cu-C3B-DO2A is irreversible. The reaction conditions for preparing Cu-64-C3B-DO2A (microwaving at high temperature) are relatively harsh compared to Cu-64-CB-TR2A (basic ethanol). The in vivo behavior of the Cu-64 complexes was evaluated in normal rats. Rapid and continual clearance of Cu-64-CB-TR2A through the blood, liver, and kidneys suggests relatively good in vivo stability, albeit inferior to Cu-64-CB-TE2A. Although Cu-64-C3B-DO2A clears continually, the initial uptake is high and only about half is excreted within 22 h, suggesting poor stability and transchelation of Cu to proteins in the blood and/or liver. These data suggest that in vitro inertness of a chelator complex may not always be a good indicator of in vivo stability.
Details
- Title: Subtitle
- Isomeric Trimethylene and Ethylene Pendant-armed Cross-bridged Tetraazamacrocycles and in Vitro/in Vivo Comparisions of their Copper(II) Complexes
- Creators
- Antoinette Y. Odendaal - University of New HampshireAshley L. Fiamengo - Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Dept Chem,Dept Biochem & Mol Biophys, St Louis, MO 63110 USARiccardo Ferdani - Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Dept Chem,Dept Biochem & Mol Biophys, St Louis, MO 63110 USAThaddeus J. Wadas - Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Dept Chem,Dept Biochem & Mol Biophys, St Louis, MO 63110 USADaniel C. Hill - Univ New Hampshire, Dept Chem, Durham, NH 03824 USAYijie Peng - Univ New Hampshire, Dept Chem, Durham, NH 03824 USAKatie J. Heroux - Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USAJames A. Golen - Univ Massachusetts, Dept Chem & Biochem, N Dartmouth, MA 02747 USAArnold L. Rheingold - Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USACarolyn J. Anderson - Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Dept Chem,Dept Biochem & Mol Biophys, St Louis, MO 63110 USAGary R. Weisman - Univ New Hampshire, Dept Chem, Durham, NH 03824 USAEdward H. Wongs - Univ New Hampshire, Dept Chem, Durham, NH 03824 USA
- Resource Type
- Journal article
- Publication Details
- Inorganic chemistry, Vol.50(7), pp.3078-3086
- DOI
- 10.1021/ic200014w
- PMID
- 21381676
- PMCID
- PMC3065210
- NLM abbreviation
- Inorg Chem
- ISSN
- 0020-1669
- eISSN
- 1520-510X
- Publisher
- Amer Chemical Soc
- Number of pages
- 9
- Grant note
- R01CA093375 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) NCI-CA093395 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 04/04/2011
- Academic Unit
- Radiology; Radiation Oncology
- Record Identifier
- 9984313079702771
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