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

✍ Scribed by Thomas Fischer; Klaus Schomäcker; Harald Schicha

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: French
• Weight: 126 KB
• Volume: 47
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.853

✦ Synopsis

Abstract

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.