Evaluation of NR-LU-10 with the Neoprobe gamma detector in a mouse model

The Neoprobe Model 1000 hand-held gamma detector, in combination with the murine monoclonal antibody (MAb) B72.3 can successfully intraoperatively target both primary and recurrent colorectal cancer. Because of the shortcomings of this system (length of time needed to clear unbound MAb and heterogeneous staining of cancer cells), new MAbs are under investigation. NR-LU-10 IgG and its FAB fragment were evaluated with the Neoprobe gamma detector in a nude mouse model. NR-LU-10 is a pancarcinoma IgG2b antibody that recognizes an oncofetal glycoprotein antigen that is expressed by most carcinomas. Animals were injected intraperitoneally with 125I-labeled IgG, 125I, or technetium 99m (99mTc)-labeled Fab fragment. The Neoprobe gamma detector and standard gamma well counts provided biodistribution and pharmacokinetic data. The Fab fragment achieved a 5:1 tumor to blood-pool background (BPB) ratio in only 66 hr, whereas the whole MAb required 14 days. Technetium did not appear to be an adequate isotope for this system because of its short half-life. Autoradiographs performed for both the 125I-labeled NR-LU-10 IgG and its 125I-labeled Fab fragment (but not 99mTc-labeled Fab) localized well in this model and gave adequate tumor to BPB and tissue ratios. Use of the 125I-labeled Fab significantly decreased the time required for clearance of the MAb radionuclide complex from the blood and tissue background, thus providing earlier tumor localization in the Radioimmunoguided Surgery (RIGS) system.