TY - JOUR T1 - PET Imaging of Norepinephrine Transporter–Expressing Tumors Using <sup>76</sup>Br-<em>meta</em>-Bromobenzylguanidine JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1472 LP - 1479 DO - 10.2967/jnumed.110.075465 VL - 51 IS - 9 AU - Shigeki Watanabe AU - Hirofumi Hanaoka AU - Ji Xin Liang AU - Yasuhiko Iida AU - Keigo Endo AU - Noriko S. Ishioka Y1 - 2010/09/01 UR - http://jnm.snmjournals.org/content/51/9/1472.abstract N2 - Meta-iodobenzylguanidine (MIBG) labeled with 123I or 131I has been widely used for the diagnosis and radiotherapy of norepinephrine transporter (NET)–expressing tumors. However, 123I/131I-MIBG has limitations for detecting small lesions because of its lower spatial resolution than PET tracers. In this study, meta-bromobenzylguanidine (MBBG) labeled with 76Br (half-life, 16.1 h), an attractive positron emitter, was prepared and evaluated as a potential PET tracer for imaging NET-expressing tumors. Methods: 76Br-MBBG was prepared by a halogen-exchange reaction between the 76Br and iodine of nonradioactive MIBG. The stability of MBBG was evaluated in vitro and in vivo by high-performance liquid chromatography analysis. Cellular uptake studies with or without NET inhibitors were performed in NET-positive PC-12 cell lines. Biodistribution studies were performed in PC-12 tumor–bearing nude mice by administration of a mixed solution of MBBG, MIBG, and 18F-FDG. The tumor was imaged using 76Br-MBBG and 18F-FDG with a small-animal PET scanner. Results: MBBG was stable in vitro, but some time-dependent dehalogenation was observed after administration in mice. MBBG showed high uptake in PC-12 tumor cells that was significantly decreased by the addition of NET inhibitors. In biodistribution studies, MBBG showed high tumor accumulation (32.0 ± 18.6 percentage injected dose per gram at 3 h after administration), and the tumor-to-blood ratio reached as high as 54.4 ± 31.9 at 3 h after administration. The tumor uptake of MBBG correlated well with that of MIBG (r = 0.997) but not with that of 18F-FDG. 76Br-MBBG PET showed a clear image of the transplanted tumor, with high sensitivity, which was different from the lesion shown by 18F-FDG PET. Conclusion: 76Br-MBBG showed high tumor accumulation, which correlated well with that of MIBG, and provided a clear PET image. These results indicated that 76Br-MBBG would be a potential PET tracer for imaging NET-expressing neuroendocrine tumors and could provide useful information for determining the indications for 131I-MIBG therapy. ER -