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Automated Preparation of [68Ga]Ga-3BP-3940 on a Synthesis Module for PET Imaging of the Tumor Microenvironment
Published on: April 25, 2025
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Thwarting Isomerization through Rigidity: A Promising HBED Derivative for the Chelation of Gallium-68
Marianna Tosato1, Matteo Boniburini2, Francesco Faglioni2
1Radiopharmaceutical Chemistry Laboratory, Nuclear Medicine Unit, AUSL-IRCCS Reggio Emilia, 42122 Reggio Emilia, Italy.
Inorganic Chemistry
|July 17, 2025
Summary
A new chelator, N,N'-(1,2-cyclohexanediamine)-N,N'-diacetic acid (HBCD), was developed to prevent isomer formation in Gallium-68 (68Ga) radiopharmaceuticals. This HBCD ligand forms a stable, single-isomer 68Ga complex, improving potential PET tracer development.
Area of Science:
- Radiochemistry
- Coordination Chemistry
- Nuclear Medicine
Background:
- The parent ligand N,N'-di(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED) can form multiple isomers upon Ga3+-complexation, potentially impacting in vivo behavior of 68Ga radiopharmaceuticals.
- A rigid cyclohexane diamine scaffold (DACH) was investigated to improve the isomeric purity of Ga3+ complexes.
Purpose of the Study:
- To synthesize and characterize the novel hexadentate acyclic ligand HBCD.
- To evaluate the Ga3+ coordination chemistry, labeling performance with 68Ga, and stability of the resulting complex.
- To assess HBCD as a potential chelator for next-generation 68Ga-based PET radiotracers.
Main Methods:
- Synthesis of the HBCD ligand.
- Acid-base behavior and Ga3+ coordination chemistry investigation.
- Labeling studies with generator-produced 68Ga under various conditions.
- Stability assessment of the [68Ga][Ga(HBCD)]- complex in physiological media.
Main Results:
- The DACH scaffold in HBCD successfully promoted the formation of a single-isomer hexacoordinated Ga3+ complex.
- Ga3+-HBCD complex showed high stability in biological media, surpassing that of DOTA.
- Efficient [68Ga]Ga3+ labeling was achieved under highly diluted and challenging radiochemical conditions.
Conclusions:
- HBCD effectively prevents isomer formation, offering a significant advantage over HBED for 68Ga radiopharmaceuticals.
- The exceptional stability of [68Ga][Ga(HBCD)]- in biological environments makes HBCD a promising chelator for PET imaging.
- HBCD represents a valuable advancement in the development of robust and reliable 68Ga-based diagnostic agents.
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