Abstract
Radiolabelled antibody conjugates enable highly targeted imaging, with the antibody affording selective binding to antigens overexpressed on specific cell types, and the conjugated radionuclide providing the detectable signal. We have shown that site-selectively modified antibody conjugates possess superior properties to conventional constructs, and antibodies labelled with radioactive metal isotopes in this fashion can be tracked in vivo, using Positron Emission Tomography (PET) imaging. This project will further develop these vital radioimmunoconjugates, by applying new conjugation and radiolabelling technology to undertake in vivo PET imaging of therapeutic antibodies (targeted IgG1 mAbs), and other classes of antibodies (IgA, IgD, IgE, IgM Abs).
References
1 Highly homogeneous antibody modification through optimisation of the synthesis and conjugation of functionalised dibromopyridazinediones, C. Bahou, D. A. Richards, A. Maruani, E. A. Love, F. Javaid, S. Caddick, J. R. Baker, V. Chudasama, Org. Biomol. Chem., 2018, 16, 1359-1366.
2 Cysteine-to-lysine transfer antibody fragment conjugation, N. Forte, I. Benni, K. Karu, V. Chudasama, J. R. Baker, Chem. Sci., 2019, 10, 10919-10924.
3 Optimisation of the dibromomaleimide (DBM) platform for native antibody conjugation by accelerated post-conjugation hydrolysis, M. Morais, J. P. M. Nunes, K. Karu, N. Forte, I. Benni, M. E. B. Smith, S. Caddick, V. Chudasama, J. R. Baker, Org. Biomol. Chem., 2017, 15, 2947-2952.
4 New Bifunctional Chelators Incorporating Dibromomaleimide Groups for Radiolabeling of Antibodies with Positron Emission Tomography Imaging Radioisotopes, M. Farleigh, T. T. Pham, Z. Yu, J. Kim, K. Sunassee, G. Firth, N. Forte, V. Chudasama, J. R. Baker, N. J. Long, C. Rivas, M. T. Ma, Bioconjugate Chem., 2021.
5 Site-specific chelator-antibody conjugation for PET and SPECT imaging with radiometals, M. Morais, M. T. Ma, Drug Discovery Today: Technologies, 2018, 30, 91-104.