TY - JOUR
T1 - Novel Chelating Agents for Zirconium-89-Positron Emission Tomography (PET) Imaging
T2 - Synthesis, DFT Calculation, Radiolabeling, and In Vitro and In Vivo Complex Stability
AU - Kang, Chi Soo
AU - Zhang, Shuyuan
AU - Wang, Haixing
AU - Liu, Yujie
AU - Ren, Siyuan
AU - Chen, Yanda
AU - Li, Jingbai
AU - Bandara, Nilantha
AU - Rogachev, Andrey Yu
AU - Rogers, Buck E.
AU - Chong, Hyun Soon
N1 - Funding Information:
This research was partly supported by the National Institutes of Health (R01CA112503 and R01EB029800 to H.-S.C.). The authors would like to thank the small animal imaging facility at Washington University School of Medicine for excellent technical assistance in conducting biodistribution studies. They would also like to acknowledge the Isotope Production Group at Washington University for production of 89Zr.
Funding Information:
This research was partly supported by the National Institutes of Health (R01CA112503 and R01EB029800 to H.-S.C.). The authors would like to thank the small animal imaging facility at Washington University School of Medicine for excellent technical assistance in conducting biodistribution studies. They would also like to acknowledge the Isotope Production Group at Washington University for production of Zr. 89
Publisher Copyright:
© 2016 American Chemical Society.
PY - 2022/10/25
Y1 - 2022/10/25
N2 - We report the synthesis and evaluation of novel chelating agents for zirconium-89 (89Zr) with positron emission tomography (PET) imaging applications. New chelating agents NODHA, NOTHA, and NODHA-PY were constructed on 1,4,7-triazacyclononane (TACN) and possess hydroxamic acid or a pyridine ring as an acyclic binding moiety. The new chelating agents were theoretically studied for complexation with Zr(IV). Structures of Zr(IV)-NODHA, Zr(IV)-NOTHA, and Zr(IV)-NODHA-PY were predicted using density functional methods. NODHA was found to form stronger bonds with Zr(IV) when compared to NOTHA and NODHA-PY. The new chelating agents were evaluated for radiolabeling efficiency in binding 89Zr. The corresponding [89Zr]Zr-labeled chelators were evaluated for complex stability in human serum. All new chelating agents rapidly bound to 89Zr in excellent radiolabeling efficiency at room temperature. Among the new [89Zr]Zr-labeled chelators evaluated, [89Zr]Zr-NODHA showed the highest stability in human serum without losing 89Zr, and [89Zr]Zr-NODHA-PY released a considerable amount of 89Zr in human serum. [89Zr]Zr-NODHA, [89Zr]Zr-NODHA-PY, and [89Zr]Zr-DFO were comparatively evaluated for in vivo complex stability by performing biodistribution studies using normal mice. [89Zr]Zr-DFO had the lowest bone uptake at all time points, while [89Zr]Zr-NODHA-PY showed poor stability in mice as evidenced by high bone accumulation at the 24 h time point. [89Zr]Zr-NODHA exhibited better renal clearance but higher bone uptake than [89Zr]Zr-DFO.
AB - We report the synthesis and evaluation of novel chelating agents for zirconium-89 (89Zr) with positron emission tomography (PET) imaging applications. New chelating agents NODHA, NOTHA, and NODHA-PY were constructed on 1,4,7-triazacyclononane (TACN) and possess hydroxamic acid or a pyridine ring as an acyclic binding moiety. The new chelating agents were theoretically studied for complexation with Zr(IV). Structures of Zr(IV)-NODHA, Zr(IV)-NOTHA, and Zr(IV)-NODHA-PY were predicted using density functional methods. NODHA was found to form stronger bonds with Zr(IV) when compared to NOTHA and NODHA-PY. The new chelating agents were evaluated for radiolabeling efficiency in binding 89Zr. The corresponding [89Zr]Zr-labeled chelators were evaluated for complex stability in human serum. All new chelating agents rapidly bound to 89Zr in excellent radiolabeling efficiency at room temperature. Among the new [89Zr]Zr-labeled chelators evaluated, [89Zr]Zr-NODHA showed the highest stability in human serum without losing 89Zr, and [89Zr]Zr-NODHA-PY released a considerable amount of 89Zr in human serum. [89Zr]Zr-NODHA, [89Zr]Zr-NODHA-PY, and [89Zr]Zr-DFO were comparatively evaluated for in vivo complex stability by performing biodistribution studies using normal mice. [89Zr]Zr-DFO had the lowest bone uptake at all time points, while [89Zr]Zr-NODHA-PY showed poor stability in mice as evidenced by high bone accumulation at the 24 h time point. [89Zr]Zr-NODHA exhibited better renal clearance but higher bone uptake than [89Zr]Zr-DFO.
UR - https://www.scopus.com/pages/publications/85140334576
U2 - 10.1021/acsomega.2c03478
DO - 10.1021/acsomega.2c03478
M3 - Article
C2 - 36312419
AN - SCOPUS:85140334576
SN - 2470-1343
VL - 7
SP - 37229
EP - 37236
JO - ACS Omega
JF - ACS Omega
IS - 42
ER -