Labelling, purification, and receptor affinity of radioactive iododiethylstilbestrol ( * I‐DES) with high specific activity and first structure analysis with nat I‐DES

Diethylstilbestrol 1 is a well known, non‐steroidal estrogen with high affinity for the estrogen receptor (ER). When labelled with an Auger‐electron emitter such as 123 I, 125 I or 77 Br 1 would be an useful radiopharmaceutical for therapy of ER‐positive mamma tumours. In the present work 1 was labelled easily and quickly with iodine by a modified chloramin T method (methanolic instead of aqueous solution), which leads to the desired product 2 in good yields (50–74%), with high radiochemical purity (>98%) and – in opposite to former attempts – very high specific activities ( 123 I‐DES: 8800 TBq/mmol, 125 I‐DES: 80 TBq/mmol, 131 I‐DES: 870 TBq/mmol). After separation by RP‐HPLC all products were characterized by NMR‐techniques ( 1 H‐, 13 C‐NMR, H,H‐COSY, and HMBC) for the very first time and the main product 3′‐Iodo‐DES 2 as well as some by‐products like the p ‐toluol‐sulfonic acid amide 3 , 1 , and 1‐chloro‐1‐(4′‐hydroxy‐phenyl)‐propene‐1 4 could be identified. The complex dissociation constant for 125 I‐DES with ER was determined by Scatchard plot and is comparable with that of 16α‐[ 125 I]‐iodoestradiol ( 125 I‐DES: K D =(2.67±1.02) × 10 −9 mol/l, 16α‐[ 125 I]‐iodoestradiol: K D =(3.92±2.27) × 10 −9 mol/l). Copyright © 2004 John Wiley & Sons, Ltd.