Repurposing carboplatin-based Pt(IV)-deferoxamine conjugates for infection theranostics

Area of Science:

• Medicinal Chemistry
• Radiopharmaceutical Chemistry
• Antimicrobial Research

Background:

• Development of multifunctional platinum(IV) complexes as prodrugs for carboplatin and deferoxamine (DFO).
• Potential for gallium-68 radiolabeling of DFO-containing complexes for molecular imaging.
• Exploitation of microbial siderophore transporters (SITs) for targeted delivery and antimicrobial activity.

Purpose of the Study:

• To synthesize and evaluate gallium-68 labeled platinum(IV)-DFO conjugates.
• To assess the potential of these conjugates for molecular imaging and targeted antimicrobial therapy against Aspergillus fumigatus (AFU).
• To investigate the theranostic applications of these novel compounds.

Main Methods:

• Radiolabeling of platinum(IV)-DFO complexes with gallium-68.
• In vitro studies including radiochemical purity, protein binding, AFU uptake assays, and MIC assays.
• In vivo studies involving stability, biodistribution, and PET imaging in a rat pulmonary aspergillosis model.

Main Results:

• Quantitative 68Ga-labeling yields with high radiochemical purity and stability.
• Demonstrated uptake in AFU and targeted accumulation in infected lung tissue in vivo.
• Favorable pharmacokinetics with rapid distribution and renal excretion, despite rapid metabolism.

Conclusions:

• Platinum(IV)-DFO conjugates can be effectively radiolabeled with 68Ga for imaging.
• These conjugates exhibit potential for targeted antimicrobial activity against AFU.
• The study highlights the promise of carboplatin-based Pt(IV)-DFO conjugates for infection theranostics.