For example, the -labeled anti-CD20 antibody has been developed for clinical usage in the treatment of malignant lymphomas.Ĭonsequently, recent efforts have been devoted to development of radiolabeled tumor-targeting biomolecules, and particularly, in evolving new and efficient synthetic methods for incorporating radionuclides into biomolecules.
More importantly, radiolabeled biomolecules have become more useful as tumor-targeting drugs for specific radiations. Radionuclide such as isotope has been employed for metastatic bone cancers 5 and isotope is used as radio-therapeutic medicine for thyroid cancers 6. On the other hand, radioisotopes (RI) have emerged as power radio-therapeutic agents and have been widely utilized in clinical practices. More critically, access to radiations targeting specifically to cancer cells remains a huge challenge. Unfortunately, such usage have been restricted to treatment of stomach cancer and bowel cancer. To improve the therapeutic effect of radiations, sensitizers using nano-materials such as gold nanoparticle, magnetic nanoparticles, and quantum dots have been developed recently 2, 3, 4. Carbon-ion based radiations 1 have been one of the most common cancer therapeutic methods. Radiogenic therapies represent an important approach to treatment of cancers. Our work provides a new and operationally simple method for introducing the isotope even in large quantities to biomolecules, thereby representing an important process for preparations of clinically relevant tumor-targeting agents for radiotherapy. Subsequently, radiolabeling of DOTA- or NOTA-attached albumin and anti-IGSF4 antibody (an anti-tumor-targeting antibody) with, a β −-emitting radionuclide, could be achieved in a highly efficient manner via a simple chelation with DOTA proving to be a more superior chelator than NOTA. By utilizing DOTA (or NOTA) containing tetrazines and the TCO-substituted aldehyde, the two click reactions, the tetrazine ligation (an inverse electron-demand Diels-Alder cycloaddition) and the RIKEN click (a rapid 6π-azaelectrocyclization), could simultaneously proceed under mild conditions to afford covalent attachment of the metal chelator DOTA or NOTA to biomolecules such as to albumin and anti-IGSF4 antibody without altering their activities.
A one-pot three-component double-click process for preparing tumor-targeting agents for cancer radiotherapy is described here.