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Basic Science Investigations |
1 Department of Radiopharmacy, Faculty of Pharmaceutical Sciences, Gent University, Gent, Belgium
2 Department of Medical Physics and Radiation Protection, Gent University, Gent, Belgium
3 Department of Pathology, N. Goormaghtigh Institute, Gent University, Gent, Belgium
4 Department of Nuclear Medicine, Gent University Hospital, Gent, Belgium.
This study reports on the in vitro evaluation, biodistribution, and dosimetry of 123I-labeled monoclonal antibody (mAb) 14C5, a new antibody-based agent proposed for radioimmunodetection of tumor growth and metastasis in vivo. Methods: 123I-mAb 14C5 was prepared by direct iodination and tested for stability in vitro. Binding assays were performed on human SK-BR-3 and HeLa carcinoma cells to investigate the antigen expression, antibody affinity, and kinetics of tracer binding. For the biodistribution and dosimetry study, 3- to 4-wk-old NMRI mice were injected intravenously with 123I-mAb 14C5 (148.0 ± 7.4 kBq per mouse) and killed at preset time intervals. Organs, blood, urine, and feces were counted for radioactivity uptake, and the data were expressed as the percentage injected dose per gram tissue (%ID/g tissue) or %ID. The MIRDOSE3.0 program was applied to extrapolate the estimated absorbed radiation doses for various organs to the human reference adult. Results: 123I-mAb 14C5 was obtained in radiochemical yields of 85.0% ± 2.5% and radiochemical purities were >97%. The iodinated antibody demonstrated good in vitro stability with 93.6% ± 0.1% of 123I-mAb 14C5 remaining intact at 24 h after radiolabeling. 123I-mAb 14C5 bound to SK-BR-3 cells (dissociation constant [Kd] 
0.85 ± 0.17 nmol/L) and HeLa cells (Kd 1.71 ± 0.17 nmol/L) with nanomolar affinity and high specificity, whereas both cell types exhibited a high CA14C5 antigen expression (maximum number of binding sites [Bmax] = 40.6 ± 5.2 and 57.1 ± 9.6 pmol/L, respectively). In mice, 123I-mAb 14C5 accumulated primarily in lungs (20.4 %ID/g), liver (15.1 %ID/g), and kidneys (11.1 %ID/g) within 5 min after injection. A delayed uptake was observed in stomach (12.8 %ID/g) and urinary bladder (8.7 %ID/g) at 3 and 6 h, respectively, after injection. Radioactivity clearance was predominantly urinary, with 44.9 ± 4.5 %ID excreted during the initial 48 h after administration (cumulative amount). The highest absorbed radiation doses determined for the human reference adult were received by the urinary bladder wall (0.1200–0.1210 mGy/MBq), liver (0.0137–0.0274 mGy/MBq), uterus (0.0196–0.0207 mGy/MBq), and lower large intestine wall (0.0139–0.0258 mGy/MBq). The average effective dose resulting from a single 123I-mAb 14C5 injection was estimated to be 0.017–0.022 mSv/MBq. Conclusion: 123I-mAb 14C5 shows good in vitro biologic activity and favorable biodistribution properties for imaging carcinomas of different origin and provides an acceptable radiation dose to the patient.
Key Words: monoclonal antibody 14C5 • cell substrate adhesion • metastasis • extracellular matrix • radioimmunodetection
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