Quantum Beam Science Directorate, Japan Atomic Energy Agency, Takasaki, Gunma, Japan.
J Nucl Med. 2010 Sep;51(9):1472-9. doi: 10.2967/jnumed.110.075465. Epub 2010 Aug 18.
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.
(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.
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.
(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.
Meta-碘苄胍（MIBG）用（123）I 或（131）I 标记，已广泛用于去甲肾上腺素转运体（NET）表达肿瘤的诊断和放射治疗。然而，（123）I/（131）I-MIBG 由于其空间分辨率低于 PET 示踪剂，因此对检测小病变具有局限性。在这项研究中，用（76）Br（半衰期 16.1 h）标记间溴苄胍（MBBG），一种有吸引力的正电子发射体，被制备并评估为成像 NET 表达肿瘤的潜在 PET 示踪剂。
通过（76）Br 和非放射性 MIBG 的碘之间的卤素交换反应制备（76）Br-MBBG。通过高效液相色谱分析评估 MBBG 的体外和体内稳定性。在 NET 阳性 PC-12 细胞系中进行了有无 NET 抑制剂的细胞摄取研究。通过给予 MBBG、MIBG 和（18）F-FDG 的混合溶液在 PC-12 肿瘤荷瘤裸鼠中进行了生物分布研究。使用小动物 PET 扫描仪对（76）Br-MBBG 和（18）F-FDG 进行肿瘤成像。
MBBG 在体外稳定，但在小鼠给药后观察到一些时相关的脱卤化作用。MBBG 在 NET 抑制剂存在下，PC-12 肿瘤细胞摄取量高，明显减少。在生物分布研究中，MBBG 在给药后 3 小时时表现出高肿瘤积聚（给药后 3 小时每克注射剂量 32.0 +/- 18.6%），并且肿瘤与血液的比值高达 54.4 +/- 31.9。MBBG 的肿瘤摄取与 MIBG（r = 0.997）相关良好，但与（18）F-FDG 无关。（76）Br-MBBG PET 清晰地显示了移植肿瘤的图像，具有高灵敏度，与（18）F-FDG PET 显示的病变不同。
（76）Br-MBBG 表现出高肿瘤积聚，与 MIBG 相关良好，并提供了清晰的 PET 图像。这些结果表明，（76）Br-MBBG 将成为成像 NET 表达神经内分泌肿瘤的潜在 PET 示踪剂，并为确定（131）I-MIBG 治疗的适应症提供有用信息。
