PET imaging of norepinephrine transporter-expressing tumors using 76Br-meta-bromobenzylguanidine.

Abstract

UNLABELLED:

Meta-iodobenzylguanidine (MIBG) labeled with (123)I or (131)I has been widely used for the diagnosis and radiotherapy of norepinephrine transporter (NET)-expressing tumors. However, (123)I/(131)I-MIBG has limitations for detecting small lesions because of its lower spatial resolution than PET tracers. In this study, meta-bromobenzylguanidine (MBBG) labeled with (76)Br (half-life, 16.1 h), an attractive positron emitter, was prepared and evaluated as a potential PET tracer for imaging NET-expressing tumors.

METHODS:

(76)Br-MBBG was prepared by a halogen-exchange reaction between the (76)Br 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 (18)F-FDG. The tumor was imaged using (76)Br-MBBG and (18)F-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 (18)F-FDG. (76)Br-MBBG PET showed a clear image of the transplanted tumor, with high sensitivity, which was different from the lesion shown by (18)F-FDG PET.

CONCLUSION:

(76)Br-MBBG showed high tumor accumulation, which correlated well with that of MIBG, and provided a clear PET image. These results indicated that (76)Br-MBBG would be a potential PET tracer for imaging NET-expressing neuroendocrine tumors and could provide useful information for determining the indications for (131)I-MIBG therapy.

• Authors: Shigeki Watanabe, Hirofumi Hanaoka, Ji Xin Liang, Yasuhiko Iida, Keigo Endo, Noriko S Ishioka
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 51 Issue 9 Pg. 1472-9 (Sep 2010) ISSN: 1535-5667 [Electronic] United States
• PMID: 20720048 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bromobenzenes
• Guanidines
• Receptors, Adrenergic
• Fluorodeoxyglucose F18
• 3-bromobenzylguanidine

Topics

• Animals
• Biological Transport
• Bromobenzenes (chemical synthesis, metabolism, pharmacokinetics)
• Fluorodeoxyglucose F18
• Gene Expression Regulation, Neoplastic
• Guanidines (chemical synthesis, metabolism, pharmacokinetics)
• Mice
• Neoplasms (diagnostic imaging, genetics, metabolism, pathology)
• PC12 Cells
• Positron-Emission Tomography (methods)
• Rats
• Receptors, Adrenergic (metabolism)