Targeted radionuclide-drug conjugates: Current status and perspectives

Area of Science:

• Nuclear Medicine
• Radiopharmaceutical Chemistry
• Oncology

Background:

• Radionuclide drug conjugates (RDCs) are innovative molecular platforms for advanced cancer diagnostics and therapeutics.
• Theranostics utilize matched diagnostic and therapeutic radionuclides on similar targeting scaffolds for personalized medicine.
• RDCs integrate targeting ligands, linkers, chelators, and radionuclides for precise tumor localization.

Purpose of the Study:

• To review recent advancements in the design of radionuclide drug conjugates (RDCs).
• To highlight key aspects of RDC development, including radionuclide choice, linker chemistry, and ligand engineering.
• To discuss clinically relevant molecular targets and associated theranostic platforms.

Main Methods:

• Review of current literature on RDC design and applications.
• Analysis of radionuclide selection criteria for diagnostic and therapeutic purposes.
• Examination of linker chemistries and ligand modification strategies for improved targeting.

Main Results:

• Discussion of clinically significant targets like PSMA, SSTRs, CCK2R, GRPR, and FAP.
• Presentation of established theranostic platforms, including ⁶⁸Ga/¹⁷⁷Lu-PSMA, ⁶⁸Ga/¹⁷⁷Lu-DOTATATE, and ¹⁸F/¹⁷⁷Lu-FAPI systems.
• Identification of RDCs' potential to enhance patient stratification and therapeutic outcomes while minimizing side effects.

Conclusions:

• RDCs show significant promise for improving cancer theranostics and precision oncology.
• Challenges remain, including tumor heterogeneity, radiochemical stability, and radionuclide production.
• Future progress hinges on multitargeting strategies, novel radionuclides, and AI-driven design.