Purpose: Both 131I- and 123I-labeled meta-iodobenzyl-guanidine (MIBG) have been widely used in the clinic for targeted imaging of the norepinephrine transporter (NET). The human NET (hNET) gene has been imaged successfully with 124I-MIBG positron emission tomography (PET) at time points of >24 h post-injection (p.i.). 18F-labeled MIBG analogs may be ideal to image hNETexpression at time points of <8 h p.i. We developed improved methods for the synthesis of known MIBG analogs, [18F]MFBG and [18F]PFBG and evaluated them in hNET reporter gene-transduced C6 rat glioma cells and xenografts. Methods: [18F]MFBG and [18F]PFBG were synthesized manually using a three-step synthetic scheme. Wild-type and hNET reporter gene-transduced C6 rat glioma cells and xenografts were used to comparatively evaluate the 18F-labeled analogs with [123I]/[124I]MIBG. Results: The fluorination efficacy on benzonitrile was predominantly determined by the position of the trimethylammonium group. The para-isomer afforded higher yields (75±7 %) than meta-isomer (21±5 %). The reaction of [ 18F]fluorobenzylamine with 1H-pyrazole-1-carboximidamide was more efficient than with 2-methyl-2-thiopseudourea. The overall radiochemical yields (decay-corrected) were 11±2 % (n =12) for [18F]MFBG and 41±12 % (n =5) for [18F]PFBG, respectively. The specific uptakes of [18F]MFBG and [18F]PFBG were similar in C6-hNET cells, but 4-fold less than that of [123I]/[124I]MIBG. However, in vivo [18F]MFBG accumulation in C6-hNET tumors was 1.6-fold higher than that of [18F]PFBG at 1 h p.i., whereas their uptakes were similar at 4 h. Despite [18F]MFBG having a 2.8-fold lower affinity to hNET and approximately 4-fold lower cell uptake in vitro compared to [123I]/[124I]MIBG, PET imaging demonstrated that [18F]MFBG was able to visualize C6-hNET xenografts better than [124I]MIBG. Biodistribution studies showed [18F]MFBG and 123I-MIBG had a similar tumor accumulation, which was lower than that of no-carrier-added [124I]MIBG, but [18F]MFBG showed a significantly more rapid body clearance and lower uptake in most non-targeting organs. Conclusion: [18F]MFBG and [18F]PFBG were synthesized in reasonable radiochemical yields under milder conditions. [ 18F]MFBG is a better PET ligand to image hNET expression in vivo at 1-4 h p.i. than both [18F]PFBG and [123I]/[ 124I]MIBG.
|Number of pages||11|
|Journal||European Journal of Nuclear Medicine and Molecular Imaging|
|State||Published - 2014|
- HNETreporter gene
- PET imaging