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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];  [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); Harry S. Truman Memorial Veterans' Hospital, Columbia, MO (United States); Univ. of Missouri, Columbia, MO (United States)
Sponsoring Organization:
Dept. of Veterans Affairs (VA) (United States); National Inst. of Health (NIH) (United States); USDOE; USDOE Office of Science (SC), Nuclear Physics (NP) (SC-26)
Grant/Contract Number:
SC0003851; SC0010283; SC0012704
OSTI ID:
1464108
Alternate ID(s):
OSTI ID: 1544917
Report Number(s):
BNL--207952-2018-JAAM
Journal Information:
Nuclear Medicine and Biology, Journal Name: Nuclear Medicine and Biology Vol. 61; ISSN 0969-8051
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English

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