Drugdu.com expert's response:

Radioactive Drug Conjugates (RDCs) represent a novel class of therapeutic agents that combine the strengths of precise targeting and potent killing capabilities. By linking radioactive nuclides to ligands (such as antibodies, peptides, small molecules, etc.) through linkers and chelators, RDCs achieve precise localization and effective eradication of target cells. Below, I will elaborate on RDCs from four aspects: definition and structure, advantages and applications, classification, as well as challenges and prospects.

I. Definition and Structure

Definition: RDCs are drug formulations that integrate radioactive nuclides with targeting molecules (ligands) through linker arms (connectors), aimed at delivering precise strikes against tumor or other disease targets.

Structure: RDC drugs consist primarily of targeting ligands, linker arms, chelators, and nuclide conjugates. The targeting ligands recognize and bind to specific target cells or tissues; linker arms connect the targeting ligands to the radioactive nuclides; chelators stabilize the radioactive nuclides, preventing their premature dissociation in vivo; and the radioactive nuclides provide the killing effect, damaging target cells through particles or rays generated during their radioactive decay.

II. Advantages and Applications

Advantages:

①Precise Targeting: RDCs can accurately identify and bind to target cells, minimizing damage to healthy cells.

②Potent Killing: Radioactive nuclides release energy within target cells, effectively killing tumor cells.

③Real-time Monitoring: Some RDCs allow real-time monitoring of treatment efficacy through imaging modalities, facilitating personalized therapy.

Applications: RDCs hold significant potential in tumor therapy. For instance, 177Lu-PSMA-617 for prostate cancer and Lutathera for neuroendocrine tumors have been approved and commercialized. Additionally, RDCs exhibit potential applications in cardiovascular diseases, neuroscience, and other fields.

III. Classification and Representative Drugs

Classification: Based on the type of targeting ligands, RDCs can be categorized into Antibody-Radionuclide Conjugates (ARCs), Small Molecule Radionuclide Conjugates (SMRCs), and Peptide Radionuclide Conjugates (PRCs).

Representative Drugs:

①Antibody-Radionuclide Conjugates (ARCs): Examples include drugs combining radioactive nuclides like iodine-131 or radium-223 with specific monoclonal antibodies.

②Small Molecule Radionuclide Conjugates (SMRCs): Drugs such as 131I-MIBG and 188Re-Lipiodol utilize small molecules' affinity for tumor carbohydrates, lipids, enzymes, etc., to concentrate radioactive nuclides at tumor sites.

③Peptide Radionuclide Conjugates (PRCs): Drugs like PR0144-CA(PSMA-617) and PR0145-CT(FAP-1) conjugate peptides with radioactive nuclides for precise targeting.

IV. Challenges and Prospects

Challenges: The development and production of RDCs face numerous challenges, including difficulties in manufacturing, distribution, and storage; limitations in technical personnel and equipment; expert personnel training; regulatory improvements; the gap between clinical trials and real-world applications; high costs; and balancing efficacy with toxicity.

Prospects: With the increasing involvement and investments of domestic and international pharmaceutical companies, technical obstacles of RDCs are expected to be gradually overcome. In the future, RDCs are poised to play a more significant role in tumor therapy, cardiovascular diseases, neuroscience, and other fields, offering patients more treatment options and hope.