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

Abstract

The clinical advantages of no-carrier-added (n.c.a) radioiodinated meta-iodobenzylguanidine ([*I]mIBG) over its carrieradded (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 3280MBq were 85±2.2% (n = 4). A twice scaled up reaction at 5340MBq 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.