Bifunctional bispidine derivatives for copper-64 labelling and positron emission tomography

Area of Science:

• Radiochemistry and Nuclear Medicine
• Organic Synthesis
• Bioconjugation Chemistry

Background:

• Bispidine derivatives offer a promising scaffold for radiometal chelation.
• Developing efficient chelators is crucial for advancing Positron Emission Tomography (PET) imaging agents.
• Copper-64 (⁶⁴Cu) is a valuable radioisotope for PET due to its favorable decay properties.

Purpose of the Study:

• To synthesize and characterize novel bispidine-based bifunctional chelators (BFCs).
• To evaluate the radiolabelling efficiency of these BFCs with ⁶⁴Cu.
• To demonstrate the utility of these BFCs for targeted imaging applications through bioconjugation.

Main Methods:

• Synthesis of bispidine derivatives L1, L2, L3 (biotinylated), and L4 (maleimide functionalized).
• Radiolabelling studies with ⁶⁴Cu under various conditions (temperature, pH, concentration).
• Evaluation of conjugation efficiency of L4 with a model peptide (GP120).

Main Results:

• Fast and efficient radiolabelling of L1 with ⁶⁴Cu achieved over 90% yield within 5 minutes at room temperature.
• Ligand L2 demonstrated good radiolabelling capacity in water (pH 4-6).
• Biotinylated L3 is suitable for pretargeting strategies, and maleimide L4 showed quantitative and regioselective conjugation to cysteine residues of GP120 under physiological conditions.

Conclusions:

• The developed bispidine-based BFCs are versatile platforms for ⁶⁴Cu radiolabelling.
• These BFCs facilitate rapid conjugation to biomolecules for targeted PET imaging.
• The findings support the potential of these novel chelators in pretargeting and molecular imaging applications.