Journal
NUCLEAR MEDICINE AND BIOLOGY
Volume 40, Issue 5, Pages 600-605Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.nucmedbio.2013.01.012
Keywords
Bi-212; Bi-213; Bifunctional chelator; Serum stability, biodistribution; Radiolabeling
Funding
- National Institutes of Health [R01CA112503]
- NIH
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Introduction: Despite the great potential of targeted alpha-radioimmunotherapy (RIT) as demonstrated by preclinical and clinical trials, limited progress has been made on the improvement of chelation chemistry for Bi-212 and Bi-213. A new bifunctional ligand 3p-C-NETA was evaluated for targeted alpha RIT using Bi-212 and Bi-213. Methods: Radiolabeling of 3p-C-NETA with Bi-205/6, a surrogate of Bi-212 and Bi-213, was evaluated at pH 5.5 and room temperature. In vitro stability of the Bi-205/6-3p-C-NETA-trastuzumab conjugate was evaluated using human serum (pH 7, 37 degrees C). Immunoreactivity and specific activity of the Bi-205/6-3p-C-NETA-trastuzumab conjugate were measured. An in vivo biodistribution study was performed to evaluate the in vivo stability and tumor targeting properties of the Bi-205/6-3p-C-NETA-trastuzumab conjugate in athymic mice bearing subcutaneous LS174T tumor xenografts. Result: The 3p-C-NETA-trastuzumab conjugate was extremely rapid in complexing with Bi-205/6, and the corresponding Bi-205/6-3p-C-NETA-trastuzumab was stable in human serum. Bi-205/6-3p-C-NETA-trastuzumab was prepared with a high specific activity and retained immunoreactivity. Bi-205/6-3p-C-NETA-trastuzumab conjugate displayed excellent in vivo stability and targeting as evidenced by low normal organ and high tumor uptake. Conclusion: The results of the in vitro and in vivo studies indicate that 3p-C-NETA is a promising chelator for RIT applications using Bi-212 and Bi-213. Further detailed in vivo evaluations of 3p-C-NETA for targeted alpha RIT are warranted. (C) 2013 Elsevier Inc. All rights reserved.
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