Large‐scale synthesis of no‐carrier‐added [ 123 I]mIBG, using two different stannylated precursors

The clinical advantages of no‐carrier‐added (n.c.a) radioiodinated meta‐iodobenzylguanidine ([*I]mIBG) over its carrier‐added (c.a.) analogue have previously been reported. A large‐scale synthesis of n.c.a. [ 123 I]mIBG was therefore investigated in this study, using a slightly adapted literature method. Two bis (t‐butyloxycarbonyl)‐protected ( bis ‐Boc) stannylated benzylguanidine precursors were prepared. The bis ‐Boc‐trimethylstannyl precursor was used to optimize radioiodination conditions. N ‐chlorosuccinimide (NCS) was used as oxidant. An HPLC method was developed to monitor radioiodination and de‐protection steps. Amounts of 200 g precursor and 2000 g NCS resulted in HPLC yields of Boc‐protected radioiodinated compounds in excess of 90%. De‐protection was carried out with trifluoroacetic acid at 110°C. A robust solid phase extraction method was developed to purify reaction mixtures. Radiochemical yields at radioactivity levels ranging between 1900 and 3280 MBq were 85±2.2% ( n =4). A twice scaled up reaction at 5340 MBq gave a similar yield. Radiochemical purities were in excess of 98% and the specific activity estimated at approximately 1 TBq.µmol −1 . Yields obtained from an HPLC‐purified bis ‐Boc‐tributylstannyl precursor were generally lower and ranged from 61 to 81%. Results obtained in this study suggest that n.c.a [ 123 I]mIBG could be synthesized on a GBq scale. Copyright © 2009 John Wiley & Sons, Ltd.