New Bifunctional Chelator 3p-C -NEPA for Potential Applications in Lu(III) and Y(III) Radionuclide Therapy and Imaging

ACS Omega
Xiang SunHyun-Soon Chong

Abstract

We have developed structurally unique bifunctional chelators in the NETA, NE3TA, and DEPA series for potential radiopharmaceutical applications. As part of our continued research efforts to generate efficient bifunctional chelators for targeted radionuclide therapy and imaging of various diseases, we designed a scorpion-like chelator that is proposed to completely saturate the coordination spheres of Y(III) and Lu(III). We herein report the synthesis and evaluation of a new chelator (3p-C-NEPA) with 10 donor groups for complexation with β-emitting radionuclides 90Y(III), 86Y(III), and 177Lu(III). The chelator was synthesized and evaluated for radiolabeling kinetics with the readily available radioisotopes 90Y and 177Lu, and the corresponding 90Y or 177Lu-radiolabeled complexes were evaluated for in vitro stability in human serum and in vivo complex stability in mice. The new chelator rapidly bound 90Y or 177Lu and formed a stable complex with the radionuclides. The new chelator 3p-C-NEPA radiolabeled with either 90Y or 177Lu remains stable in human serum without dissociation for 10 days. 177Lu-labeled 3p-C-NEPA produced a favorable in vivo biodistribution profile in normal mice.

References

Mar 23, 2000·Seminars in Radiation Oncology·S J Knox, R F Meredith
Jun 3, 2004·Nature Reviews. Drug Discovery·Diane E MilenicMartin W Brechbiel
Jun 4, 2004·European Journal of Nuclear Medicine and Molecular Imaging·Andreas HelischPeter Bartenstein
Oct 4, 2007·Bioorganic & Medicinal Chemistry Letters·Hyun-Soon ChongXiankai Sun
Jan 8, 2009·Bioconjugate Chemistry·Tapan K Nayak, Martin W Brechbiel
Apr 7, 2011·Chemical Communications : Chem Comm·Hyun-Soon ChongAnzhi Dai
Nov 1, 2011·European Journal of Organic Chemistry·Hyun-Soon ChongChi Soo Kang
Dec 17, 2015·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Ningjie WuHyun-Soon Chong
Jan 12, 2017·The New England Journal of Medicine·Jonathan StrosbergUNKNOWN NETTER-1 Trial Investigators

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Citations

May 30, 2021·Current Opinion in Chemical Biology·Deborah Sneddon, Bart Cornelissen

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Methods Mentioned

BETA
NMR
column chromatography

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