ArticleNuclear medicine and biology2013
Methodology for labeling proteins and peptides with lead-212 (212Pb).
Article in Nuclear medicine and biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 71 citations in OpenAlex.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
introductionAlpha particles possess an exquisite degree of cytotoxicity when employed for targeted α-particle therapy (TAT) or radioimmunotherapy (RIT). (212)Pb, which acts as an in vivo generator of the α-emitting nuclide (212)Bi has shown great promise in pre-clinical studies when used to label the HER2 binding antibody, trastuzumab. Currently, the first RIT clinical trial employing (212)Pb radiolabeled trastuzumab is in progress. This report provides detailed current protocol operations and steps that were generated for use in the clinical trial as well as the relevant pre-clinical experimentation, and describes in detail the labeling of proteins or peptides with (212)Pb as provided via a (224)Ra based generator system.
methods(212)Pb was eluted from the (224)Ra/(212)Pb generator using hydrochloric acid (2M). The generator eluate was evaporated and digested with nitric acid (8M) followed by extraction of the (212)Pb with dilute nitric acid (0.1M). The dilute nitric acid solution of (212)Pb was used to label the immunoconjugate Trastuzumab-TCMC (2-(4-isothiocyanatobenzyl-1,4,7,10-tetraaza-1,4,7,10,tetra-(2-carbamonylmethyl)-cyclododecane) at pH5.5.
resultsElution of (212)Pb from the generator was efficient yielding>90% of available (212)Pb. Trastuzumab-TCMC was efficiently labeled with a radiochemical yield of 94% ± 4% (n=7) by ITLC and an isolated yield of 73% ± 3% (n=7).
conclusionsThe results show the feasibility of generating radioimmunoconjugates and peptide conjugates for use as in vivo α generator systems in the clinic. The technology holds promise in applications involving the treatment of minimal disease such as micrometastases and residual tumor after surgical debulking, hematological cancers, infections, and compartmental cancers, such as ovarian cancer.
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