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Shelf-Life of e-Lysyl-3-(Trimethylstannyl)Benzamide Immunoconjugates, Precursors for At-211 Labeling of Antibodies

Emma Aneheim ; Jenny Halleröd ; Per Albertsson ; H. Jensen ; Stellan Holgersson (Institutionen för kemi och kemiteknik, Kärnkemi) ; Sture Lindegren
Cancer Biotherapy and Radiopharmaceuticals (1084-9785). Vol. 30 (2015), 1, p. 41-45.
[Artikel, refereegranskad vetenskaplig]

Astatine-211 is possibly the most promising radionuclide for targeted alpha-particle therapy when it comes to the treatment of occult disseminated cancer. Preclinical research has proven effective, and patient studies have been initiated based on these results. However, a lack of production capacity and the complex radiochemistry of At-211 are major obstacles for research and prospective clinical applications. In the present study, astatination of immunoconjugates, already prepared well in advance before radiolabeling, was performed to investigate the possibility of formulating a kit-like reagent for the production of At-211 radiopharmaceuticals. The shelf-life of e-lysyl-3-(trimethylstannyl)benzamide immunoconjugates was evaluated, that is, the effect of different storage times on the quality of the immunoconjugates. The quality being referred to is the capacity to maintain a good radiochemical yield and good cell-binding property after labeling with At-211. The stability of the conjugates was found to be pH dependent with high stability at pH >= 7 and less stability at pH <= 5.5. The immunoconjugates (based on trastuzumab) could be kept for more than 3 months in a phosphate buffered saline solution (pH 7.4) at 4 degrees C before labeling, without compromising the quality of the labeled product. The conjugates are also unaffected by storage at -20 degrees C. Conjugates with a good shelf-life compatible with distant shipping as well as improved radiochemistry are important steps to facilitate further clinical progress with At-211.

Nyckelord: immunoconjugate, labeling, antibodies, shelf-life, astatine-211



Denna post skapades 2015-03-06. Senast ändrad 2015-03-09.
CPL Pubid: 213443

 

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Institutioner (Chalmers)

Institutionen för kliniska vetenskaper, sektionen för onkologi, radiofysik, radiologi och urologi, Avdelningen för radiofysik (GU)
Institutionen för kliniska vetenskaper, sektionen för onkologi, radiofysik, radiologi och urologi, Avdelningen för onkologi (GU)
Institutionen för kemi och kemiteknik, Kärnkemi

Ämnesområden

Farmakologi
Radiologi

Chalmers infrastruktur