The Evaluation of (1 R ,4 R ,7 R ,10 R )-α,α',α″,α‴-Tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic Acid (DOTMA) as a Chelator for Zirconium-89

Darpan N Pandya; Pere Miro; Michael A Sinnwell; George B Crull; Thaddeus J Wadas

doi:10.3390/molecules30204129

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The Evaluation of (1 R ,4 R ,7 R ,10 R )-α,α',α″,α‴-Tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic Acid (DOTMA) as a Chelator for Zirconium-89

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The Evaluation of (1 R ,4 R ,7 R ,10 R )-α,α',α″,α‴-Tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic Acid (DOTMA) as a Chelator for Zirconium-89

Darpan N Pandya, Pere Miro, Michael A Sinnwell, George B Crull and Thaddeus J Wadas

Molecules (Basel, Switzerland), Vol.30(20), 4129

10/19/2025

DOI: 10.3390/molecules30204129

PMCID: PMC12566511

PMID: 41157146

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Abstract

Recently, macrocycles such as 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) have been observed to form zirconium-89 (89Zr: t½ = 78.4 h, β+: 22.8%, Eβ+max = 901 keV; EC: 77%, Eγ = 909 keV)-complexes with excellent in vivo stability. In this report, we describe (1R,4R,7R,10R)-α,α′,α″,α‴-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTMA) as an 89Zr chelator. Using [89Zr]ZrCl4, [89Zr]Zr-DOTMA was prepared in 99% radiochemical yield and a molar activity of 1055 ± 6 MBq/µmol. In vitro studies revealed a LogP value of −2.97± 0.02 and a radiometal complex that was inert when challenged with 1000-fold excess EDTA or high concentrations of biologically relevant metal ions. Finally, biodistribution studies revealed that the radiometal complex demonstrated in vivo behavior that was like [89Zr]Zr-DOTA and superior to [89Zr]Zr-DFO. Despite these promising observations, the elevated temperature required to form the [89Zr]Zr-DOTMA complex and the lack of derivatives available for bioconjugation will require additional ligand engineering to improve its utility for future nuclear medicine applications.

Radiochemistry

positron emission tomography

zirconium-89

tetraazamacrocycle

Details

Title: Subtitle: The Evaluation of (1 R ,4 R ,7 R ,10 R )-α,α',α″,α‴-Tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic Acid (DOTMA) as a Chelator for Zirconium-89
Creators: Darpan N Pandya - University of Iowa
Pere Miro - University of Iowa
Michael A Sinnwell - University of Iowa
George B Crull - University of Iowa
Thaddeus J Wadas - University of Iowa
Resource Type: Journal article
Publication Details: Molecules (Basel, Switzerland), Vol.30(20), 4129
DOI: 10.3390/molecules30204129
PMID: 41157146
PMCID: PMC12566511
NLM abbreviation: Molecules
ISSN: 1420-3049
eISSN: 1420-3049
Publisher: MDPI
Grant note: 2016-BIG-6524 / North Carolina Biotechnology Center W81XWH-19-1-0046 / Department of Defense R21-CA227709 / NIH HHS
Language: English
Date published: 10/19/2025
Academic Unit: Radiology; Radiation Oncology; Chemistry
Record Identifier: 9985019149402771

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