PT  - JOURNAL ARTICLE
AU  - Douglas J. Rowland
AU  - Zhude Tu
AU  - Jinbin Xu
AU  - Datta Ponde
AU  - Robert H. Mach
AU  - Michael J. Welch
TI  - Synthesis and In Vivo Evaluation of 2 High-Affinity <sup>76</sup>Br-Labeled σ<sub>2</sub>-Receptor Ligands
DP  - 2006 Jun 01
TA  - Journal of Nuclear Medicine
PG  - 1041--1048
VI  - 47
IP  - 6
4099  - http://jnm.snmjournals.org/content/47/6/1041.short
4100  - http://jnm.snmjournals.org/content/47/6/1041.full
SO  - J Nucl Med2006 Jun 01; 47
AB  - 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.