Synthesis of 18F-Fluorobenzylguanidine analogues via SNAr substitution

1510 Objectives 124I/123I-MIBG have a limited capacity of sequential imaging of hNET-expressing cells in patients. Garg et al have shown that hydrophilic 18F-MFBG (or PFBG) is recognized and transported by hNET-expressing cells (Nucl Med Bio, 21:97-101, 1994). However, the radiosynthesis of 18F-MFBG (or PFBG) is a multi-step, labor intensive and time-consuming reaction that has impeded wider use of these tracers in the clinic. To simply the radiosynthesis, we designed and synthesized a novel diaryliodonium salt precursors in order to facilitate a two-step, one pot radiosynthesis. Methods Diaryliodonium salts precursors were synthesized from commercially available Iodobenzyl ethyl amine in three steps. These intermediate products were characterized by MS and [1H]NMR. Using anhydrous kryptofix-K18F as the starting material, fluorination was optimized by varying temperature (60oC to 130oC) and solvent (DMF and AcCN). After hydrolysis, 18F-MFBG (or PFBG) was purified by semipreparative HPLC. In-vitro evaluation was performed with hNET-expressing C6 and C6-WT cells. Results Stable diaryliodonium salts were obtained with an over-all yield of 40%, and further characterization confirmed the expected structures. 18F-MFBG (or PFBG) was prepared successfully in 1 hour with a radiochemical yield of 20% (decay-corrected). Radiochemical purity of both radiotracers is greater than 99%. In-vitro studies showed that 18F-MFBG (or PFBG) specifically accumulated in C6-hNET cells, which can be competitively blocked with an excess of MIBG. Conclusions Meta and para-118F-Fluorobenzylguanidines were synthesized successfully in a two-step reaction using diaryliodonium salts. In-vitro results showed that these agents are promising for imaging hNET reporter gene expression, and will likely have clinical application for PET imaging of neuroendocrine tumors