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

To investigate adrenomedullary radiopharmaceuticals for positron emission tomography (PET), we have developed no-carrier-added m-(ω-[ ¹⁸F]fluoroalkyl)benzylguanidines, m-ω-[ ¹⁸F]Fluoroalkyl)benzylguanidines were prepared in two steps starting from N,N′-bis(tert-butyloxycarbonyl)-N″(ω -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 °C were reduced to half of that at 37 °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.