In vitro and in vivo trackable titanocene-based complexes using optical imaging or SPECT

Area of Science:

• Radiochemistry
• Oncology
• Materials Science

Background:

• Titanocene complexes offer unique chemical properties for developing novel therapeutic and diagnostic agents.
• Radiometals like Indium-111 are crucial for developing effective radiotheranostic agents.
• The synthesis of complex ligands, such as titanocene-DOTA, presents significant chemical challenges.

Purpose of the Study:

• To synthesize and characterize a novel Ti/¹¹¹In-heterometallic radiotheranostic agent and its non-radioactive analogues.
• To evaluate the antiproliferative activity of these complexes against various cancer cell lines.
• To assess the in vitro and in vivo behavior of the Ti/¹¹¹In complex for potential theranostic applications.

Main Methods:

• Synthesis of titanocene-DOTA and titanocene-BODIPY ligands.
• Characterization of novel Ti/In, Ti/Lu, Ti/Y, and Ti/¹¹¹In complexes.
• In vitro antiproliferative assays on A2780, B16F1, and PC3 cancer cell lines.
• In vivo biodistribution, uptake, and excretion studies in mice using the Ti/¹¹¹In complex.
• In vitro tracking using confocal microscopy with fluorescent complexes.

Main Results:

• Successful synthesis of the first titanocene-DOTA ligand and its metal complexes.
• Demonstrated antiproliferative effects of the complexes on tested cancer cell lines.
• Initial in vivo studies in mice provided data on biodistribution and excretion of the Ti/¹¹¹In complex.
• In vitro tracking confirmed the cellular uptake and localization of fluorescent analogues.

Conclusions:

• The developed titanocene-based complexes, including the Ti/¹¹¹In radiotheranostic agent, show potential for cancer theranostics.
• The novel titanocene-DOTA ligand is a versatile platform for developing radiometal complexes for imaging and therapy.
• Further studies are warranted to optimize the theranostic potential of these novel titanium complexes.