No-carrier added *I-meta-iodobezylguanidine suitable for clinical use: synthesis and separation studies from its precursor meta-trimethylsilylbenzylguanidine

¹³¹I-Meta-iodobezylguanidine (mIBG) is a proven theranostic agent selectively used for targeted radiotherapy of tumors such as phaeochromocytoma and neuroblastoma. Both carrier added and carrier free preparations are in clinical use worldwide. However, the synthesis and isolation of the latter preparation remotely from its precursor in bulk quantities for patient use (> 100 mCi) is highly challenging. This paper describes preliminary studies in the preparation of carrier-free 125-I-meta-iodobezylguanidine using precursor meta trimethylsilylbenzylguanidine. Two different labelling approaches; peracid and chloramine-T oxidation were evaluated using 2-3 μmol of precursor and around 300 μCi of I-125 as NaI. The product was purified using a Dowex ion-exchanger to remove unreacted ¹²⁵I-. This was then analyzed by HPLC and purified using C-18 cartridge (10 μm particle size) to remove unreacted m-trimethylsilyl benzylguanidine from the radiolabeled mIBG. Radiochemical yield determined using electrophoresis and HPLC characterization was more than 90% in both the cases. The labelled product was purified using C 18 cartridge using triethyl ammonium phosphate buffer (0.3 %, pH 4) where different fractions of 1mL each were collected to determine the separation of labelled ¹²⁵I-mIBG from its precursor. The precursor eluted out completely in two fractions whereas subsequent fractions showed the presence of radiolabelled product only. Though, 40% of the radiolabeled activity was found to overlap with the precursor material in first two fractions, remaining 60% of the labelled product was of ncalevel as determined by HPLC. nca-¹²⁵I-mIBG obtained is suitable for clinical use and is easily adaptable for mass scale production. However, further steps are underway to increase the separation efficiency of labelled mIBG and its precursor trimethylsilyl derivative. (author)