Improved in vivo stability of actinium-225 macrocyclic complexes

Kim A. Deal, Ila A. Davis, Saed Mirzadeh, Stephen Kennel, Martin W. Brechbiel

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

The favorable nuclear properties of actinium-225 (225Ac) have led to proposal of this isotope for use in radioimmunotherapy. In an effort to reduce the toxicity of free 225Ac, a series of ligands were evaluated for stability in vivo. Loss of 225Ac from acyclic chelating agents resulted in high liver uptake and poor whole body clearance. The macrocyclic ligands c- DOTA, PEPA, and HEHA were evaluated, and 225Ac-HEHA showed exceptional stability in vivo. 225Ac chelated with EDTA, DTPA, DOTA, or PEPA permitted substantial accumulation of the radionuclide to the liver, while the 225Ac-HEHA complex was essentially excreted within minutes of administration. The preparation of the ligands and radiolabeled complexes and the biodistribution results will be discussed.

Original languageEnglish (US)
Pages (from-to)2988-2992
Number of pages5
JournalJournal of Medicinal Chemistry
Volume42
Issue number15
DOIs
StatePublished - Jul 29 1999

Fingerprint

Actinium
Ligands
Radioimmunotherapy
Pentetic Acid
Liver
Chelating Agents
Edetic Acid
Radioisotopes
Isotopes
actinium 1,4,7,10,13,16-hexaazacyclohexadecane-N,N',N'',N''',N'''',N'''''-hexaacetic acid

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Improved in vivo stability of actinium-225 macrocyclic complexes. / Deal, Kim A.; Davis, Ila A.; Mirzadeh, Saed; Kennel, Stephen; Brechbiel, Martin W.

In: Journal of Medicinal Chemistry, Vol. 42, No. 15, 29.07.1999, p. 2988-2992.

Research output: Contribution to journalArticle

Deal, KA, Davis, IA, Mirzadeh, S, Kennel, S & Brechbiel, MW 1999, 'Improved in vivo stability of actinium-225 macrocyclic complexes', Journal of Medicinal Chemistry, vol. 42, no. 15, pp. 2988-2992. https://doi.org/10.1021/jm990141f
Deal, Kim A. ; Davis, Ila A. ; Mirzadeh, Saed ; Kennel, Stephen ; Brechbiel, Martin W. / Improved in vivo stability of actinium-225 macrocyclic complexes. In: Journal of Medicinal Chemistry. 1999 ; Vol. 42, No. 15. pp. 2988-2992.
@article{b17e044863a44a3788135add6ebe9125,
title = "Improved in vivo stability of actinium-225 macrocyclic complexes",
abstract = "The favorable nuclear properties of actinium-225 (225Ac) have led to proposal of this isotope for use in radioimmunotherapy. In an effort to reduce the toxicity of free 225Ac, a series of ligands were evaluated for stability in vivo. Loss of 225Ac from acyclic chelating agents resulted in high liver uptake and poor whole body clearance. The macrocyclic ligands c- DOTA, PEPA, and HEHA were evaluated, and 225Ac-HEHA showed exceptional stability in vivo. 225Ac chelated with EDTA, DTPA, DOTA, or PEPA permitted substantial accumulation of the radionuclide to the liver, while the 225Ac-HEHA complex was essentially excreted within minutes of administration. The preparation of the ligands and radiolabeled complexes and the biodistribution results will be discussed.",
author = "Deal, {Kim A.} and Davis, {Ila A.} and Saed Mirzadeh and Stephen Kennel and Brechbiel, {Martin W.}",
year = "1999",
month = "7",
day = "29",
doi = "10.1021/jm990141f",
language = "English (US)",
volume = "42",
pages = "2988--2992",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "15",

}

TY - JOUR

T1 - Improved in vivo stability of actinium-225 macrocyclic complexes

AU - Deal, Kim A.

AU - Davis, Ila A.

AU - Mirzadeh, Saed

AU - Kennel, Stephen

AU - Brechbiel, Martin W.

PY - 1999/7/29

Y1 - 1999/7/29

N2 - The favorable nuclear properties of actinium-225 (225Ac) have led to proposal of this isotope for use in radioimmunotherapy. In an effort to reduce the toxicity of free 225Ac, a series of ligands were evaluated for stability in vivo. Loss of 225Ac from acyclic chelating agents resulted in high liver uptake and poor whole body clearance. The macrocyclic ligands c- DOTA, PEPA, and HEHA were evaluated, and 225Ac-HEHA showed exceptional stability in vivo. 225Ac chelated with EDTA, DTPA, DOTA, or PEPA permitted substantial accumulation of the radionuclide to the liver, while the 225Ac-HEHA complex was essentially excreted within minutes of administration. The preparation of the ligands and radiolabeled complexes and the biodistribution results will be discussed.

AB - The favorable nuclear properties of actinium-225 (225Ac) have led to proposal of this isotope for use in radioimmunotherapy. In an effort to reduce the toxicity of free 225Ac, a series of ligands were evaluated for stability in vivo. Loss of 225Ac from acyclic chelating agents resulted in high liver uptake and poor whole body clearance. The macrocyclic ligands c- DOTA, PEPA, and HEHA were evaluated, and 225Ac-HEHA showed exceptional stability in vivo. 225Ac chelated with EDTA, DTPA, DOTA, or PEPA permitted substantial accumulation of the radionuclide to the liver, while the 225Ac-HEHA complex was essentially excreted within minutes of administration. The preparation of the ligands and radiolabeled complexes and the biodistribution results will be discussed.

UR - http://www.scopus.com/inward/record.url?scp=0033614957&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033614957&partnerID=8YFLogxK

U2 - 10.1021/jm990141f

DO - 10.1021/jm990141f

M3 - Article

C2 - 10425108

AN - SCOPUS:0033614957

VL - 42

SP - 2988

EP - 2992

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 15

ER -