Synthesis and in vivo evaluation of 2 high-affinity 76Br-labeled σ2-receptor ligands

Douglas J. Rowland, Zhude Tu, Jinbin Xu, Datta Ponde, Robert H. Mach, Michael J. Welch

Research output: Contribution to journalArticle

38 Scopus citations


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.

Original languageEnglish
Pages (from-to)1041-1048
Number of pages8
JournalJournal of Nuclear Medicine
Issue number6
StatePublished - 2006


  • Cancer
  • F-FLT
  • Micro-PET
  • Small animal
  • σ-receptor

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