METABOLIZABLE IN-111 CHELATE CONJUGATED ANTI-IDIOTYPE MONOCLONAL ANTIBODY FOR RADIOIMMUNODETECTION OF LYMPHOMA IN MICE

We investigated the relative biological properties of In-111 labeled monoclonal antibodies (MOAB) coupled with a conventional bifunctional chelate (BC) and with a new enzyme metabolizable bifunctional chelate (BCM). A rat IgG2A MOAB (7D4) against idiotype from a mouse B-cell lymphoma (38C-13) was chelate coupled then In-111 labeled just prior to use. C3H mice bearing 38C-13 flank tumors 100–500 mg in size were injected I.V. with labeled MOAB and imaged and/or sacrificed for organ counting at 24 or 48 hours. Control tumor mice were given In-111 chelate labeled rat anti-dinitrophenol IgG2A MOAB (DNP-BC). All tumors were clearly visualized with 7D4-BC and 7D4-BCM but not with DNP-BC. Organ distributions at 24 hours were as follows:% DOSE/GRAM TUMOR/BLOOD RATIO (TBR)7D4-BC 7D4-BCM DNP-BCBlood 3.0 1.4 7.9 7D4-BC 1.8Tumor 5.0 3.5 3.7 7D4-BCM 2.4Liver 18.9 12.4 14.8 DNP-BC 0.5Spleen 10.9 4.8 7.4 (TBRʼs as high as 8.3 were seen at 48 hours)Kidneys 4.0 7.9 14.4Use of BCM resulted in a substantial lowering of blood background, a shorter biological half life (43% excretion in 24 hours vs. 16%) and an increase in the TBR at the expense of a moderate decrease in absolute tumor uptake. The versatile chemistry of our C-1 substituted EDTA BCʼs provides for a variety of other possible enzyme cleavable groups (e.g., peptide bonds) for further investigation.