Synthesis and In Vivo Evaluation of 2 High-Affinity 76Br-Labeled σ2-Receptor Ligands

Journal of Nuclear Medicine

Douglas J. Rowland¹  Zhude Tu¹  Jinbin Xu¹  Datta Ponde¹  Michael J. Welch¹  Robert H. Mach¹ 

[1] Department of Radiology, Washington University in St. Louis, Saint Louis, Missouri Department of Radiology, Washington University in St. Louis, Saint Louis, Missouri Department of Radiology, Washington University in St. Louis, Saint Louis, Missouri

关键词: σ₂-receptor;    ¹⁸F-FLT;    cancer;    small animal;    microPET;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

The σ2-receptor has been shown to be upregulated in proliferating tumors cells. The purpose of this study was to compare 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) and 2 new 76Br-radiolabeled compounds that have a high affinity and selectivity for the σ2-receptor. These are 5-bromo-N-(4-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)butyl)-2,3-dimethoxybenzamide (compound (1)) and 5-bromo-N-(2-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)ethyl)-2-methoxybenzamide (compound (2)). Methods: Two σ2-receptor−binding ligands were prepared, from the corresponding tributylstannyl precursors using standard electrophilic chemistry, 76Br-compound (1) (76Br-1) and 76Br-compound (2) (76Br-2). 18F-FLT, 76Br-1, and 76Br-2 were compared using allograft tumors of the EMT-6 cell line (mouse mammary adenocarcinoma) in biodistribution studies at 5 min, 0.5, 1, and 2 h. Imaging of 76Br-1 and 18F-FLT was also performed at 2 and 1 h, respectively. Results: 76Br-1 and 76Br-2 were synthesized with yields between 50% and 70% with high specific activity. Both compounds showed uptake into the tumor with tumor-to-normal tissue ratios of 76Br-1 being greater than both 76Br-2 and 18F-FLT. Except for the liver and kidney, all ratios were greater than 1 and uptake into the tumor was shown with microPET imaging for 76Br-1. Conclusion: We were able to synthesize two 76Br-radiolabeled compounds with a high yield and specific activity that target the σ2 receptor with high affinity and selectivity. The studies presented show that both of the flexible benzamide compounds can identify EMT-6 breast tumors in vivo. 76Br-1 also has higher tumor-to-normal tissue ratios when compared with 76Br-2 and 18F-FLT. The high affinity and low nonspecific binding of 76Br-1 indicates that it can be a potential PET radiotracer for imaging solid tumors.

【 授权许可】

Unknown