Radiolabeling, biodistribution, and dosimetry of (123)I-mAb 14C5: a new mAb for radioimmunodetection of tumor growth and metastasis in vivo.

UNLABELLED: This study reports on the in vitro evaluation, biodistribution, and dosimetry of (123)I-labeled monoclonal antibody (mAb) 14C5, a new antibody-based agent proposed for radioimmunodetection of tumor growth and metastasis in vivo. METHODS: (123)I-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 (123)I-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: (123)I-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 (123)I-mAb 14C5 remaining intact at 24 h after radiolabeling. (123)I-mAb 14C5 bound to SK-BR-3 cells (dissociation constant [K(d)] approximately 0.85 +/- 0.17 nmol/L) and HeLa cells (K(d) approximately 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 [B(max)] = 40.6 +/- 5.2 and 57.1 +/- 9.6 pmol/L, respectively). In mice, (123)I-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 (123)I-mAb 14C5 injection was estimated to be 0.017-0.022 mSv/MBq. CONCLUSION: (123)I-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.

Apoptosis-detecting radioligands: current state of the art and future perspectives.

This review provides a critical and thorough overview of the radiopharmaceutical development and in vivo evaluation of all apoptosis-detecting radioligands that have emerged so far, along with their possible applications in nuclear medicine. The following SPECT and PET radioligands are discussed: all forms of halogenated Annexin V (i.e. (123)I-labelled, (124)I-labelled, (125)I-labelled, (18)F-labelled), (99m)Tc/(94m)Tc-labelled Annexin V derivatives using different chelators and co-ligands (i.e. BTAP, Hynic, iminothiolane, MAG(3), EDDA, EC, tricarbonyl, SDH) or direct (99m)Tc-labelling, (99m)Tc-labelled Annexin V mutants and (99m)Tc/(18)F-radiopeptide constructs (i.e. AFIM molecules), (111)In-DTPA-PEG-Annexin V, (11)C-Annexin V and (64)Cu-, (67)Ga- and (68)Ga-DOTA-Annexin V. In addition, the potential role and clinical relevance of anti-PS monoclonal antibodies and other alternative apoptosis markers are reviewed, including: anti-Annexin V monoclonal antibodies, radiolabelled caspase inhibitors and substrates and mitochondrial membrane permeability targeting radioligands. Nevertheless, major emphasis is placed on the group of Annexin V-based radioligands, in particular (99m)Tc-Hynic-Annexin V, since this molecule is by far the most extensively investigated and best-characterised apoptosis marker at present. Furthermore, the newly emerging imaging modalities for in vivo detection of programmed cell death, such as MRI, MRS, optical, bioluminescent and ultrasound imaging, are briefly described. Finally, some future perspectives are presented with the aim of promoting the development of potential new strategies in pursuit of the ideal cell death-detecting radioligand.