HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JNM Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rowland, D. J. Articles by Welch, M. J. Search for Related Content PubMed PubMed Citation Articles by Rowland, D. J. Articles by Welch, M. J.

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

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

Correspondence: For correspondence or reprints contact: Michael J. Welch, PhD, Washington University in St. Louis, 510 S. Kingshighway, Campus Box 8225, Saint Louis, MO 63110-1076. E-mail: welchm{at}wustl.edu

The ₂-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 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(1H)-yl)ethyl)-2-methoxybenzamide (compound (2)). Methods: Two ₂-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 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. 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.

Key Words: ₂-receptor • ¹⁸F-FLT • cancer • small animal • microPET

Related articles in JNM:

This Month in JNM

JNM 2006 47: 11a-12a. [Full Text]  

This article has been cited by other articles:

				C. Zeng, S. Vangveravong, J. Xu, K. C. Chang, R. S. Hotchkiss, K. T. Wheeler, D. Shen, Z.-P. Zhuang, H. F. Kung, and R. H. Mach Subcellular Localization of Sigma-2 Receptors in Breast Cancer Cells Using Two-Photon and Confocal Microscopy Cancer Res., July 15, 2007; 67(14): 6708 - 6716. [Abstract] [Full Text] [PDF]