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Abstract
Strategies that aim at targeting radionuclides to human cancers have made important advances in recent years, and the need for improved delivery systems represents one of the current challenges in nuclear oncology. In this report, we have used the non-toxic B-subunit of Shiga toxin as a delivery tool. The synthesis of a maleimide-DOTA bifunctional chelating agent and a method for site-specific labeling a B-subunit variant with radioactive metals such as 111indium were developed. Biodistribution studies in mice revealed the accumulation of [111In]STxB in kidney and lung. Quantitatively and qualitatively similar results were obtained with iodinated STxB. The distribution half-life of [125I]STxB was 0.31 hours, and its elimination half-life was 9.54 hours, leading to a mean residence time of 12.8 hours, which is surprisingly high for such a small molecule. In a mouse model of spontaneous adenocarcinomatosis, a significant accumulation of [ In]STxB was observed in tumor tissue. Autoradiography of the excised digestive tube showed the accumulation of the vector in distinct tumor nodules. In conclusion, our study documents the potential use of STxB as a vector for tumor delivery of radionuclides. The relevance of these data with respect to the human situation, particularly kidney accumulation of [ In]STxB, is discussed.
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