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.