Pursuing theranostics: a multimodal architecture approach.

Area of Science:

• Nuclear Medicine
• Radiochemistry
• Materials Science

Background:

• Theranostics combines diagnosis and therapy using identical targeting vectors and chelating systems.
• Current theranostic approaches require more adaptable chelate systems for novel targeting strategies.
• Developing flexible scaffolds is crucial for advancing multimodal radiopharmaceuticals.

Purpose of the Study:

• To create a versatile, phosphazene-based multimodal architecture for theranostic applications.
• To design customizable scaffolds capable of chelating multiple radionuclides.
• To evaluate the stability and radiolabeling efficiency of novel multimodal compounds.

Main Methods:

• Synthesis of a six-arm phosphazene core scaffold.
• Attachment of DTPA and/or DFO chelating motifs using click chemistry.
• Characterization of terbium complexes for luminescence and structural confirmation.
• Metal displacement titration for validating heterometallic labeling capabilities.
• In vitro stability assessments and radiolabeling with 161Tb and 89Zr.

Main Results:

• Two multimodal compounds, pDbDt and pDbDtDf, were synthesized using the phosphazene core.
• Terbium complexes exhibited strong luminescence, acting as organic antennas.
• Structures confirmed via metal displacement titration, showing heterometallic labeling potential.
• Compounds demonstrated high thermal and biological stability in vitro.
• High molar activity achieved upon radiolabeling with 161Tb and 89Zr, including 1:1 heterometallic labeling.

Conclusions:

• The developed phosphazene-based multimodal architecture offers a highly customizable platform for theranostics.
• This scaffold facilitates the coupling of both diagnostic and therapeutic radionuclides.
• The system shows significant promise for developing advanced heterometallic radiopharmaceuticals.