Novel ligands based on adenoviral knob protein for molecular imaging


Suresh C Srivastava, George E Meinken, K. Springer, and P. Freimuth. Medical Department, Brookhaven National Laboratory, Building 801, P.O. Box 5000, Upton, NY 11973
To use adenovirus (Ad) protein scaffolds for developing novel ligands for molecular imaging, we have focused on the recombinant "knob" domain of the Ad fiber, which interacts with its in-vivo cellular receptor CAR. Results on biodistribution of I-131-labeled knob in mice showed preferential uptake in CAR-binding tissues (liver, kidney, heart, and lung), but blood and whole body clearance were rapid. When mice were injected with excess unlabeled knob, the level of I-131-knob in blood increased with a corresponding decrease in metabolic deiodination. I-131 labeled knob mutants, unable to interact with CAR, were retained longer in blood and had slower metabolism. These data demonstrate that bioengineered knob-based ligands with inhibited CAR-binding activity would have slower breakdown and circulate long enough to specifically interact with their molecular targets in tumors or other tissues. Supported by U.S. DOE (OBER) under Contract #DE-AC02-98CH10886.