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Feng, Yutian; DeGraffenreid, Anthony J.; Brookhaven National Laboratory; Phipps, Michael D.; Rold, Tammy L.
Brookhaven National Laboratory (BNL), Upton, NY (United States); University of Missouri, Columbia, MO (United States); Harry S. Truman Memorial Veterans' Hospital, Columbia, MO (United States). Funding organisation: USDOE Office of Science - SC, Nuclear Physics - NP (SC-26) (United States); National Institute of Health (NIH) (United States); Dept. of Veterans Affairs - VA (United States)2018
Brookhaven National Laboratory (BNL), Upton, NY (United States); University of Missouri, Columbia, MO (United States); Harry S. Truman Memorial Veterans' Hospital, Columbia, MO (United States). Funding organisation: USDOE Office of Science - SC, Nuclear Physics - NP (SC-26) (United States); National Institute of Health (NIH) (United States); Dept. of Veterans Affairs - VA (United States)2018
AbstractAbstract
[en] Trithiol chelates are suitable for labeling radioarsenic (72As: 2.49 MeV β+, 26 h; 77As: 0.683 MeV β-, 38.8 h) to form potential theranostic radiopharmaceuticals for PET imaging and therapy. In this paper, to investigate the in vivo stability of trithiol chelates complexed with no carrier added (nca) radioarsenic, a bifunctional trithiol chelate was developed, and conjugated to bombesin(7–14)NH2 as a model peptide. A trithiol-BBN(7–14)NH2 bioconjugate and its arsenic complex were synthesized and characterized. The trithiol-BBN(7–14)NH2 conjugate was radiolabeled with 77As, its in vitro stability assessed, and biodistribution studies were performed in CF-1 normal mice of free [77As]arsenate and 77As-trithiol- BBN(7–14)NH2. The trithiol-BBN(7–14)NH2 conjugate, its precursors and its As-trithiol-BBN(7–14)NH2 complex were fully characterized. Radiolabeling studies with nca 77As resulted in over 90% radiochemical yield of 77As-trithiol-BBN, which was stable for over 48 h. Biodistribution studies were performed with both free [77As]arsenate and Sep-Pak® purified 77As-trithiol-BBN(7–14)NH2. Compared to the fast renal clearance of free [77As]arsenate, 77As-trithiol-BBN(7–14)NH2 demonstrated increased retention with clearance mainly through the hepatobiliary system, consistent with the lipophilicity of the 77As-trithiol-BBN(714)NH2 complex. Finally, the combined in vitro stability of 77As-trithiol-BBN(7–14)NH2 and the biodistribution results demonstrate its high in vivo stability, making the trithiol a promising platform for developing radioarsenic-based theranostic radiopharmaceuticals.
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BNL--207952-2018-JAAM; OSTIID--1464108; SC0012704; SC0003851; SC0010283; 5 T32-EB004822; Available from https://www.osti.gov/servlets/purl/1464108; DOE Accepted Manuscript full text, or the publishers Best Available Version will be available free of charge after the embargo period; arXiv:1804.04564; Country of input: United States
Record Type
Journal Article
Journal
Nuclear Medicine and Biology; ISSN 0969-8051;
; v. 61; p. 1-10

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ARSENIC ISOTOPES, BETA DECAY RADIOISOTOPES, BETA-MINUS DECAY RADIOISOTOPES, BETA-PLUS DECAY RADIOISOTOPES, CLEARANCE, COMPLEXES, COMPUTERIZED TOMOGRAPHY, DAYS LIVING RADIOISOTOPES, DIAGNOSTIC TECHNIQUES, ELECTRON CAPTURE RADIOISOTOPES, EMISSION COMPUTED TOMOGRAPHY, EXCRETION, INTERMEDIATE MASS NUCLEI, ISOTOPES, NUCLEI, ODD-EVEN NUCLEI, ODD-ODD NUCLEI, RADIOISOTOPES, TOMOGRAPHY
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