Michael J. McCall

Metabolizable 111in chelate conjugated anti-idiotype monoclonal antibody for radioimmunodetection of lymphoma in mice

The relative biological properties of 111In-labeled monoclonal antibodies (MoAb) coupled with a conventional bifunctional chelate (BC) and a new, enzyme metabolizable, bifunctional chelate (BCM) were investigated. A rat IgG2a MoAb against idiotype from a mouse B-cell lymphoma was utilized. Mice bearing B-cell lymphomas in the subcutaneous tissues of the flank were given IV-injections of labeled MoAb and imaged or killed for organ counting at 24 h or 48 h. Rat anti-dinitrophenyl IgG2a MoAb and non-specific polyclonal mouse IgG were used as controls. Compared to BC, the use of BCM resulted in a substantial decrease in blood background activity, a shorter biological half-life and an increase in tumor to blood ratio at the expense of a moderate decrease in absolute tumor uptake. The versatile chemistry of these C-1 substituted bifunctional chelates provides a variety of possible enzyme cleavable moieties for further investigation.

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-BC Blood 3.0 1.4 7.9 7D4-BC 1.8 Tumor 5.0 3.5 3.7 7D4-BCM 2.4* Liver 18.9 12.4 14.8 DNP-BC 0.5 Spleen 10.9 4.8 7.4 *(TBRs as high as 8.3 were seen at 48 hours) Kidneys 4.0 7.9 14.4 Use 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 BCs provides for a variety of other possible enzyme cleavable groups (e.g., peptide bonds) for further investigation.