Potential and Practical Adrenomedullary PET Radiopharmaceuticals as an Alternative to mIodobenzylguanidine: m-(omega-[18F]Fluoroalkyl)benzylguanidines

To investigate adrenomedullary radiopharmaceuticals for positron emission tomography (PET), we have developed no-carrier-added m-(omega-[18F]fluoroalkyl)benzylguanidines. m-(omega[18F]Fluoroalkyl)benzylguanidines were prepared in two steps starting from N,Nʹ-bis(tertbutyloxycarbonyl)-Nʹ ʹ-(omega-methanesulfonyloxyalkyl)benzylguanidines in 20-30% radiochemical yields (decay corrected for 100 min) and with high radiochemical purity (>97%) and shown to be stable (>90%) in an in vitro metabolic stability assay. The binding of m-(3-[18F]fluoropropyl)benzylguanidine ([18F]3) to SK-N-SH human neuroblastoma cells was temperature dependent, and binding levels at 4 (degree)C were reduced to half of that at 37 (degree)C, which was similar to the reduction rate observed for [123I]MIBG. Tissue distribution studies in mice showed the highest uptake in the adrenals (%ID/g = 27.2 +- 5.0%) with relatively high uptake in the myocardium (%ID/g = 9.3 +- 0.5%). The results suggest that this radiotracer holds promise as a useful adrenomedullary radiopharmaceutical for PET imaging.