Development of a new radiolabel (203Pb) and new chelating agents for labeling monoclonal antibodies for imaging.

High liver uptake and slow body clearance presently limit the usefulness of 111In labeled antibodies for tumor imaging. We have investigated 203Pb as an alternative and better antibody label. The DTPA and cyclohexyl EDTA (CDTA) conjugates of an anticolon carcinoma antibody, 17-1A, were labeled (bicyclic anhydride method) with 203Pb and 111In with 60 and 90 per cent labeling yields, respectively. The biodistribution of 203Pb-17-1A conjugates was compared with the corresponding 111In-labeled preparations and with 203Pb-DTPA, 203Pb-nitrate and nonrelevant antibody controls in normal and human tumor (SW948) xenografted nude mice at 24 and 96 h. 203Pb labeled CDTA and DTPA antibody conjugates gave similar in vivo distributions. Even though the lead bound to these chelate-antibody conjugates was more labile in serum and in vivo, compared with indium, it cleared much faster from the liver and the whole body. A new series of chelating agents based on the incorporation of a trans-1,2-diaminocyclohexane moiety into the carbon backbone of polyaminocarboxylates is being synthesized. These are expected to provide stronger complexing ability for lead and produce greater in vivo stability. These ligands are also expected to be superior to EDTA and DTPA for labeling antibodies with other radiometals, including indium.