title: Clinical evaluation of tumor targeting with a high-affinity, anticarcinoembryonic-antigen-specific, murine monoclonal antibody, MN-14.
abstract: BACKGROUND
  The authors previously reported that an anticarcinoembryonic antigen antibody against a carcinoembryonic antigen (CEA)-specific epitope is preferred for clinical investigations. They developed a second generation, CEA-specific murine monoclonal antibody (MoAb), MN-14 (IMMU-14), that has a tenfold higher affinity. This report summarizes the initial clinical experience with the new MoAb.
  
  
  METHODS
  MN-14 immunoglobulin G (IgG) (0.5-6.0 mg) was labeled with radioactive iodine (I131) (5-80 mCi) and injected into 22 patients with cancer. External scintigraphy was used to determine targeting in patients with low and highly elevated plasma CEA. Quantitative external scintigraphy methods were used to determine organ and tumor clearance rates and absorbed radiation doses. Targeting data were correlated with several factors, including MoAb protein dose, plasma CEA, and relative tumor burden.
  
  
  RESULTS
  Despite more than 80% complexation with plasma CEA of more than 500 ng/ml, all known tumor sites were disclosed by external scintigraphy. The overall sensitivity of tumor targeting on a lesion basis was 89%. The residence time in the blood was predicted by body weight (P = 0.05) and the log of plasma CEA (P = 0.043). The absorbed dose to the red marrow and total body could be predicted by the body weight of the patient, but no other factor contributed significantly to the clearance rate or absorbed dose to the organs. Individual tumors received an average dose of 9.3 +/- 6.4 cGy/mCi. The absorbed dose to the tumors was negatively correlated to the weight of the tumor, and the percent uptake in the tumor was positively correlated to the estimated total tumor burden. Patients injected with approximately 5 mg of MN-14 IgG were more likely to have anti-mouse antibodies (HAMA) develop than were patients who were injected with less MoAb.
  
  
  CONCLUSIONS
  These results suggest that MN-14 targets tumors effectively, even in the presence of elevated circulating CEA. Additional studies are necessary to determine if an advantage for the higher affinity MN-14 MoAb, compared with the lower affinity NP-4 MoAb, can be appreciated clinically.
authors.affiliation: Garden State Cancer Center, Newark, New Jersey.
authors.forename: R M
authors.initials: RM
authors.lastname: Sharkey
authors.forename: D M
authors.initials: DM
authors.lastname: Goldenberg
authors.forename: S
authors.initials: S
authors.lastname: Murthy
authors.forename: H
authors.initials: H
authors.lastname: Pinsky
authors.forename: R
authors.initials: R
authors.lastname: Vagg
authors.forename: D
authors.initials: D
authors.lastname: Pawlyk
authors.forename: J A
authors.initials: JA
authors.lastname: Siegel
authors.forename: G Y
authors.initials: GY
authors.lastname: Wong
authors.forename: P
authors.initials: P
authors.lastname: Gascon
authors.forename: D O
authors.initials: DO
authors.lastname: Izon
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis; D002272:Carcinoembryonic Antigen / Q000097:blood / Q000276:immunology*; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008875:Middle Aged; D009369:Neoplasms / Q000000981:diagnostic imaging*; D016719:Radioimmunodetection; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D000888:Antibodies, Anti-Idiotypic; D002272:Carcinoembryonic Antigen; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes