Light induced chemical reactions (so-called photochemical activation) can be done under mild conditions which are physiological for biologically active macromolecules. We have recently used such photo-chemistry to attach small organic molecules to antibodies. The photolinker contain side chains which can act as chelaters for metals.
The aim of this proposal is to use this technique to produce radiolabeled antibodies for tumor imaging through photoincorporation of chelated 111Indium3+. Preliminary experiments showed that the photolinker attaches in a specific fashion to a discrete site on immunoglobulins of different isotopes and specificities. Furthermore, it was demonstrated that photolinked antibodies retain the full capacity to bind to antigen. In the present proposal we plan to produce radiolabeled anti-tumor antibodies against a mouse and a human B cell lymphoma cell line and to use these radiolabeled antibodies to image tumor in situ by scintigraphic techniques. We expect to show that our photoactivation technique will produce radiolabeled antibodies against cancers with superior tumor-uptake specificity. Such radiolabeled antibodies are much needed and valuable tools for cancer diagnosis and therapy.
Development of a novel method to generate chelated radioactive metal containing antibodies has great commercial value because current methods have limitations. Radiolabeled anti-tumor antibodies are important diagnostic and therapeutic tools in cancer research and therapy.
| Lou, D; Kohler, H (1998) Enhanced molecular mimicry of CEA using photoaffinity crosslinked C3d peptide. Nat Biotechnol 16:458-62 |
| Pavlinkova, G; Rajagopalan, K; Muller, S et al. (1997) Site-specific photobiotinylation of immunoglobulins, fragments and light chain dimers. J Immunol Methods 201:77-88 |
