The importance of radiochemical purity: Cellular binding and internalization of different radiometal chlorides in prostate cancer cells.

Markus Mitterhauser, Marcus Hacker, Julia Raitanen, Lena Palm, Theresa Balber

Journal: Nuclear medicine and biology 2024;138-139():108949

PMID: 39284237

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Abstract

Radiometals play an important role in nuclear medicine, both for imaging and therapy. Binding studies represent an important step in the development of new radiolabeled ligands, as valuable insights into the binding properties can be gained. However, this technique requires high radiochemical purity, otherwise results may lead to wrong assumptions or misinterpretations of affinities or uptake rates. Therefore, this in vitro study aimed at investigating the cell binding and internalization characteristics of different radiometal chlorides ([In]InCl, [Ga]GaCl and [Lu]LuCl) commonly applied in nuclear medicine, as well as the clinically applied [Lu]Lu-PSMA-I&T in comparison, by using prostate cancer cells. PC-3 and LNCaP cells were incubated with 100 kBq of the respective radiometal chloride or [Lu]Lu-PSMA-I&T for 1 h. For [Lu]LuCl, nuclei isolations and colloid determinations in saline and cell medium were also performed. Results showed that [In]InCl and [Ga]GaCl bind and are internalized up to 3 % to PC-3 and LNCaP cells, whereas [Lu]LuCl showed cell binding of up to 25 %, internalization up to 2.5 % and a nuclear uptake below 0.3 %. In comparison, [Lu]Lu-PSMA-I&T showed only 3 % total cell binding to LNCaP cells. Further analysis of [Lu]LuCl stability in NaCl and cell medium showed only low amounts of colloids, which are not increasing over time, and negligible unspecific binding to the used cell culture plates. In conclusion, the results demonstrate the importance of high radiochemical purity, especially with regard to Lu-177 labeled compounds. Even if radiopharmaceuticals comply with common release-criteria, significant uptake can be derived from [Lu]LuCl impurities and lead to wrong estimations of a compound's uptake behavior. Assuming an experimental result of 2 % membrane binding of the applied product, and 5 % residual [Lu]LuCl in the final product (thereof 25 % membrane binding, as described above), would lead to 1.25 % membrane binding resulting from [Lu]LuCl and only 0.75 % from the radiopharmaceutical.

Address: Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, 1090 Vienna, Austria; Vienna Doctoral School in Chemistry (DoSChem), University of Vienna, 1090 Vienna, Austria; Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, 1090 Vienna, Austria.; Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, 1090 Vienna, Austria.; Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, 1090 Vienna, Austria.; Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, 1090 Vienna, Austria; Joint Applied Medicinal Radiochemistry Facility, Medical University of Vienna, University of Vienna, 1090 Vienna, Austria.; Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, 1090 Vienna, Austria; Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, 1090 Vienna, Austria; Joint Applied Medicinal Radiochemistry Facility, Medical University of Vienna, University of Vienna, 1090 Vienna, Austria. Electronic address: [email protected].

DOI: 10.1016/j.nucmedbio.2024.108949