Radiolabeled (4-Fluoro-3-Iodobenzyl)Guanidine Improves Imaging and Targeted Radionuclide Therapy of Norepinephrine Transporter-Expressing Tumors.

18F- or 131I-labeled (4-fluoro-3-iodobenzyl)guanidine (FIBG) has been a promising yet unattainable derivative of radioiodine-labeled meta-iodobenzylguanidine (MIBG), because of the complex radiofluorination method. In this study, we proposed a 2-step radiosynthetic method to obtain 18F-FIBG and evaluated the diagnostic and therapeutic potential of 18F-FIBG and 131I-FIBG in a pheochromocytoma model (PC-12). Methods:18F-FIBG was prepared from a (mesityl)(aryl)iodonium salt precursor in the presence of a copper catalyst. Biodistribution studies, PET imaging, and a therapeutic study were performed on the PC-12 xenograft mice with either 18F- or 131I-FIBG. The association between the therapeutic effect and the tumor uptake of pretherapy 18F-FIBG PET was also evaluated. Results: The copper-mediated radiofluorination method readily yielded 18F-FIBG, as well as its regioisomer, 18F-IFBG. The isolated 18F-FIBG showed a higher accumulation in the PC-12 xenograft tumor than in any other tissue. The high tumor uptake of 18F-FIBG allowed clear tumor visualization in the PET images as early as 1 h after injection, with an excellent tumor-to-background ratio. A biodistribution study with 131I-FIBG revealed its higher and prolonged retention in the tumor in comparison with 125I-MIBG. As a result, a therapeutic dose of 131I-FIBG delayed tumor growth significantly more than did 131I-MIBG. The tumor uptake of 18F-FIBG was proportional to the therapeutic effect of 131I-FIBG. Conclusion: These results suggest the potential usefulness of FIBG as a diagnostic and therapeutic agent for the management of norepinephrine transporter (NET)-expressing tumors.