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Title: A trithiol bifunctional chelate for 72,77As: A matched pair theranostic complex with high in vivo stability

Journal Article · · Nuclear Medicine and Biology
 [1];  [2];  [1];  [3];  [1];  [4];  [1];  [5];  [6];  [3]; ORCiD logo [7]
  1. Univ. of Missouri, Columbia, MO (United States). Dept. of Chemistry
  2. Univ. of Missouri, Columbia, MO (United States). Dept. of Chemistry; Brookhaven National Lab. (BNL), Upton, NY (United States). Medical Isotope Research and Production Program (MIRP). Collider-Accelerator Dept.
  3. Harry S. Truman Memorial Veterans' Hospital, Columbia, MO (United States). Research Service
  4. Univ. of Missouri, Columbia, MO (United States). Molecular Interaction Core
  5. Univ. of Missouri, Columbia, MO (United States). Research Reactor Center (MURR); Brookhaven National Lab. (BNL), Upton, NY (United States). Medical Isotope Research and Production Program (MIRP). Collider-Accelerator Dept.
  6. Univ. of Missouri, Columbia, MO (United States). Research Reactor Center (MURR)
  7. Univ. of Missouri, Columbia, MO (United States). Dept. of Chemistry. Research Reactor Center (MURR)
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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.

Research Organization:
Brookhaven National Lab. (BNL), Upton, NY (United States); Univ. of Missouri, Columbia, MO (United States); Harry S. Truman Memorial Veterans' Hospital, Columbia, MO (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Nuclear Physics (NP); National Inst. of Health (NIH) (United States); Dept. of Veterans Affairs (VA) (United States)
Grant/Contract Number:
SC0012704; SC0003851; SC0010283; 5 T32-EB004822
OSTI ID:
1464108
Alternate ID(s):
OSTI ID: 1544917
Report Number(s):
BNL-207952-2018-JAAM; TRN: US1902361
Journal Information:
Nuclear Medicine and Biology, Vol. 61; ISSN 0969-8051
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 13 works
Citation information provided by
Web of Science

References (27)

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Related Subjects

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
62 RADIOLOGY AND NUCLEAR MEDICINE
trithiol bioconjugate
arsenic trithiol
no carrier added 77As
radiolabeling
biodistributions