D. Rowland, Z. Tu, Jinbin Xu
Jun 1, 2006
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Journal
The Journal of Nuclear Medicine
Abstract
The σ 2 -receptor has been shown to be upregulated in proliferating tumors cells. The purpose of this study was to compare 3'-deoxy-3'- 1 8 F-fluorothymidine ( 1 8 F-FLT) and 2 new 7 6 Br-radio-labeled compounds that have a high affinity and selectivity for the σ 2 -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(1 H)-yl)ethyl)-2-methoxybenzamide (compound (2)). Methods: Two σ 2 -receptor-binding ligands were prepared, from the corresponding tributylstannyl precursors using standard electrophilic chemistry, 7 6 Br-compound (1) ( 7 6 Br-1) and 7 6 Br-compound (2) ( 7 6 Br-2). 1 8 F-FLT, 7 6 Br-1, and 7 6 Br-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 7 6 Br-1 and 1 8 F-FLT was also performed at 2 and 1 h, respectively. Results: 7 6 Br-1 and 7 6 Br-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 7 6 Br-1 being greater than both 7 6 Br-2 and 1 8 F-FLT. Except for the liver and kidney, all ratios were greater than 1 and uptake into the tumor was shown with microPET imaging for 7 6 Br-1. Conclusion: We were able to synthesize two 7 6 Br-radiolabeled compounds with a high yield and specific activity that target the σ 2 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. 7 6 Br-1 also has higher tumor-to-normal tissue ratios when compared with 7 6 Br-2 and 1 8 F-FLT. The high affinity and low nonspecific binding of 7 6 Br-1 indicates that it can be a potential PET radiotracer for imaging solid tumors.