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Updated: Feb 28, 2026
Synthesis of Functionalized Magnetic Nanoparticles, Their Conjugation with the Siderophore Feroxamine and its Evaluation for Bacteria Detection
Published on: June 16, 2020
67Ga-labeled deferoxamine derivatives for imaging bacterial infection: Preparation and screening of functionalized
Joseph A Ioppolo1, Deanna Caldwell1, Omid Beiraghi1
1Department of Chemistry and Chemical Biology, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4M1, Canada.
Introduction:
Deferoxamine (DFO) is a siderophore that bacteria use to scavenge iron and could serve as a targeting vector to image bacterial infection where current techniques have critical limitations. [67Ga]-DFO, which is a mimetic of the corresponding iron complex, is taken up by bacteria in culture, however in vivo it clears too rapidly to allow for imaging of infection. In response, we developed several new DFO derivatives to identify those that accumulate in bacteria, and at sites of infection, and that could potentially have improved pharmacokinetics.
Methods:
A library of DFO derivatives was synthesized by functionalizing the terminal amine group of DFO using three different carbamate-forming reactions. Uptake of [67Ga]-DFO and the 67Ga-labeled derivatives by bacteria and the biodistribution of lead compounds were studied.
Results:
67Ga-labeled DFO derivatives were prepared and isolated in >90% radiochemical yield and >95% radiochemical purity. The derivatives had significant but slower uptake rates in Staphylococcus aureus than [67Ga]-DFO (6% to 60% of the control rate), with no uptake for the most lipophilic derivatives. Biodistribution studies in mice with a S. aureus infection in one thigh revealed that the ethyl carbamate derivative had an excellent infected-to-non-infected ratio (11:1), but high non-specific localization in the gall bladder, liver and small intestine.
Conclusions:
The work reported shows that it is possible to functionalize DFO-type siderophores and retain active uptake of the 67Ga-labeled complexes by bacteria. Novel 67Ga-labeled DFO derivatives were specifically taken up by S. aureus and selected derivatives demonstrated in vivo localization at sites of infection. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: 67Ga-labeled DFO derivatives were actively transported by bacteria using the iron-siderophore pathway, suggesting that it is possible to develop siderophore-based radiopharmaceuticals for imaging bacterial infection.
Insights
New deferoxamine (DFO) derivatives show promise for imaging bacterial infections. These novel compounds are taken up by bacteria and can localize at infection sites, potentially improving diagnostic capabilities.
Area of Science:
- Biomedical Imaging
- Radiopharmaceutical Chemistry
- Infectious Disease Diagnostics
Background:
- Deferoxamine (DFO), a bacterial siderophore, can target iron-scavenging pathways.
- Current imaging techniques for bacterial infections have limitations.
- DFO's rapid in vivo clearance hinders its use for infection imaging.
Purpose of the Study:
- Develop novel DFO derivatives for improved bacterial infection imaging.
- Identify DFO derivatives with enhanced bacterial uptake and in vivo localization.
- Optimize pharmacokinetic properties for effective infection detection.
Main Methods:
- Synthesized a library of DFO derivatives via carbamate-forming reactions.
- Labeled DFO and its derivatives with Gallium-67 (67Ga).
- Assessed bacterial uptake and conducted biodistribution studies in infected mice.
Main Results:
- 67Ga-labeled DFO derivatives achieved high radiochemical yield and purity.
- Derivatives showed significant, albeit slower, uptake in *Staphylococcus aureus* compared to 67Ga-DFO.
- An ethyl carbamate derivative demonstrated a high infected-to-non-infected ratio in vivo, despite non-specific organ uptake.
Conclusions:
- Functionalized DFO-type siderophores retain bacterial uptake capabilities.
- Novel 67Ga-labeled DFO derivatives are specifically taken up by *S. aureus*.
- Siderophore-based radiopharmaceuticals show potential for imaging bacterial infections via iron-siderophore transport.
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