Radiolabelling Pt-based quadruplex DNA binders via click chemistry

Area of Science:

• Medicinal Chemistry
• Molecular Biology
• Radiochemistry

Background:

• Guanine-rich sequences form G-quadruplexes (G4), crucial in biological functions and as drug targets.
• Small molecules, including metal complexes with Schiff base ligands, are developed to target G4 structures.
• Platinum(II)-salphen complexes are established G4 DNA binders.

Purpose of the Study:

• To functionalize a platinum(II)-salphen G4 DNA binder with radiolabeled complexes.
• To evaluate the in vivo distribution and tumor accumulation of the radiolabeled conjugate.

Main Methods:

• Synthesis of a platinum(II)-salphen complex functionalized with a radiolabeled indium-111 (¹¹¹In) conjugate.
• In vivo single-photon emission computed tomography (SPECT) imaging in a mouse tumor model.

Main Results:

• Successful radiolabeling of the platinum-salphen complex with ¹¹¹In.
• SPECT imaging demonstrated significant accumulation of the Pt-salphen-¹¹¹In conjugate within the tumor.

Conclusions:

• The radiolabeled Pt-salphen-¹¹¹In conjugate shows promising tumor-targeting capabilities.
• This approach holds potential for developing G4-targeting diagnostic and therapeutic agents.