A trithiol bifunctional chelate for (72,77)AS : A matched pair theranostic complex with high in vivo stability

作者：Feng Yutian; DeGraffenreid Anthony J; Phipps Michael D; Rold Tammy L; Okoye Nkemakonam C; Gallazzi Fabio A; Barnes Charles L; Cutler Cathy S; Ketring Alan R; Hoffman Timothy J; Jurisson Silvia S^*

来源：Nuclear Medicine and Biology, 2018, 61: 1-10.

DOI：10.1016/j.nucmedbio.2018.03.001

• Trithiol bioconjugate
• Arsenic trithiol
• No carrier added As-77
• Radiolabeling
• Biodistributions

Introduction: Trithiol chelates are suitable for labeling radioarsenic (As-72: 2.49 MeV beta(+), 26 h;As- 77: 0.683 MeV beta(-), 38.8 h) to form potential theranostic radiopharmaceuticals for PET imaging and therapy. 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.
Methods: A trithiol-BBN(7-14)NH(2 )bioconjugate and its arsenic complex were synthesized and characterized. The trithiol-BBN(7-14)NH2 conjugate was radiolabeled with( 77)As, its in vitro stability assessed, and biodistribution studies were performed in CF-1 normal mice of free [As-77]arsenate and( 77)As-trithiol- BBN (7-14)NH2.
Results: The trithiol-BBN(7-14)NH(2 )conjugate, its precursors and its As-trithiol-BBN(7-14)NH2 complex were fully characterized. Radiolabeling studies with nca(77)As resulted in over 90% radiochemical yield of( 77)As-trithiol-BBN, which was stable for over 48 h. Biodistribution studies were performed with both free [As-77]arsenate and Sep-Pak (R) purified( 77)As-trithiol-BBN(7-14)NH2. Compared to the fast renal clearance of free [As-77]arsenate,As-77-trithiol-BBN(7-14)NH2 demonstrated increased retention with clearance mainly through the hepatobiliary system, consistent with the lipophilicity of the( 77)As-trithiol-BBN(714)NH(2 )complex.
Conclusion: The combined in vitro stability of As-77-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.

• 出版日期2018-6