UC San Diego

This thesis reports the development of a metal chelating bioorthogonal tetrazine diethylene triamine pentaacetic acid (DTPA) dextran probe that is highly reactive with transcyclooctene modified monoclonal antibodies. Using this probe, we performed multistep labeling of the A33 antigen on human colon cancer cells using transcyclooctene modified anti-A33 monoclonal antibodies followed by tetrazine DTPA dextran probes. Confocal imaging demonstrates the expected surface modification of A33 by fluorescently labeled tetrazine DTPA dextran. The availability of the DTPA chelating group allows rapid metallation of the reactive polymers with the positron emitting radionuclide gallium-68 (68Ga) and it was demonstrated that 68Ga tetrazine dextrans can be used to label the A33 antigen on cancer cells using the bioorthogonal multistep approach. We have characterized the biodistribution of the 68Ga tetrazine dextran and have imaged its uptake in vivo using positron emission tomography (PET) imaging. Tetrazine modified metal- chelating polymers may prove to be important probes for multistep imaging of antigens using short-lived and highly convenient PET radionuclides such as 68Ga