(212)Pb-conjugated anti-rat HER2/neu antibody against a neu-N derived murine mammary carcinoma cell line: cell kill and RBE in vitro.

(212)Pb-conjugated anti-rat HER2/neu antibody against a neu-N derived murine mammary carcinoma cell line: cell kill and RBE in vitro.
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DOI:
10.1080/09553002.2022.2033341
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发表时间:
2022
影响因子:
2.6
通讯作者:
--
中科院分区:
医学3区
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--
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In the current work, the RBE of a 212Pb conjugated anti-HER2/neu antibody construct has been evaluated, in vitro, by colony formation assay. The RBE was estimated by comparing two absorbed dose-survival curves: the first obtained from the conjugated 212Pb experiments (test radiation), the second obtained by parallel experiments of single bolus irradiation of external beam (reference radiation). Mammary carcinoma NT2.5 cells were treated with (0-3.70) kBq/ml of radiolabeled antibody. Non-specific binding was assessed with addition of excess amount of unlabeled antibody. The colony formation curves were converted from activity concentration to cell nucleus absorbed dose by simulating the decay and transport of all daughter and secondary particles of 212Pb, using the Monte Carlo code GEANT 4. The radiolabeled antibody yielded an RBE of 8.3 at 37 % survival and a survival independent RBE (i.e., RBE2) of 9.9. Unbound/untargeted 212Pb-labeled antibody, as obtained in blocking experiments yielded minimal alpha-particle radiation to cells. These results further highlight the importance of specific targeting towards achieving tumor cell kill and low toxicity to normal tissue.
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