Large‐scale synthesis of no‐carrier‐added [123I]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. ¹²³I]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 ¹²³I]mIBG could be synthesized on a GBq scale. Copyright © 2009 John Wiley & Sons, Ltd.