The pretargeting technique referred to as the Affinity Enhancement System (
AES) uses bispecific antibodies and radiolabeled bivalent haptens that bind
cooperatively to target cells in vivo. Experimental and clinical data demo
nstrate that DTPA bivalent haptens can deliver large radiation doses to tum
or cells with high tumor to normal tissue contrast ratios and long activity
residence time in tumors, Preliminary clinical results of radioimmunothera
py of medullary thyroid carcinomas and lung cancers look promising. Very en
couraging results in biodistribution and radioimmunotherapy experiments in
animals have been obtained with new haptens bearing two histamine-hemisucci
nate suitable for I-131, Tc-99m and Re-188 labeling. Targeting isotopes to
double antigen positive tumor cells provides a binding enhancement that inc
reases specificity for tumor cells as compared to single antigen targeting
on normal cells. This approach may be beneficial for targeting isotopes to
B type acute lymphoblastic leukemia and Burkitt lymphoma, as well as others
tumors co-expressing two markers of low specificity, and might increase tu
mor irradiation with minimal irradiation of normal cells.