Synthesis of ring- and side-chain-substituted m-iodobenzylguanidine analogues

With the goal of developing MIBG analogues with improved targeting properti es especially for oncologic applications, several radioiodinated ring- and side-chain-substituted MIBG analogues were synthesized. Except for 3-[I-131 ]iodo-4-nitrobenzylguanidine and N-hydroxy-3-[I-131]iodobenzylguanidine, th e radio-iodinated analogues were prepared at no-carrier-added levels from t heir respective tin precursors. The radiochemical yields generally were in the range of 70-90% except for 3-amino-5- [I-131]iodobenzylguanidine for wh ich a radiochemical yield of about 40% was obtained. While the silicon prec ursor N-1,N-2-bis(tert-butyloxycarbonyl)-N-1-(4-nitro-3-trimethylsilylbenzy l)guanidine did not yield 3-[I-131]iodo-4-nitrobenzylguanidine, its deprote cted derivative, N-1-(4-nitro-3-trimethylsilylbenzyl)guanidine was radioiod inated in a modest yield of 20% providing 3-[I-131]iodo-4-nitrobenzylguanid ine. Exchange radioiodination of 3-iodo-4-nitrobenzylguanidine gave 3-[I-13 1]iodo-4-nitrobenzylguanidine in 80% radiochemical yield. No-carrier-added [I-131]NHIBG was prepared from its silicon precursor N-1-hydroxy-N-3-(3-tri methylsilylbenzyl)guanidine in 85% radiochemical yield.