NEW IODINATED PROGESTINS AS POTENTIAL LIGANDS FOR PROGESTERONE-RECEPTOR IMAGING IN BREAST-CANCER - PART 1 - SYNTHESIS AND IN-VITRO PHARMACOLOGICAL CHARACTERIZATION

Citation
Jc. Vandenbos et al., NEW IODINATED PROGESTINS AS POTENTIAL LIGANDS FOR PROGESTERONE-RECEPTOR IMAGING IN BREAST-CANCER - PART 1 - SYNTHESIS AND IN-VITRO PHARMACOLOGICAL CHARACTERIZATION, Nuclear medicine and biology, 25(8), 1998, pp. 781-789
Citations number
45
Categorie Soggetti
Radiology,Nuclear Medicine & Medical Imaging
ISSN journal
09698051
Volume
25
Issue
8
Year of publication
1998
Pages
781 - 789
Database
ISI
SICI code
0969-8051(1998)25:8<781:NIPAPL>2.0.ZU;2-3
Abstract
Five putative iodinated progesterone receptor (PR) binding ligands wer e synthesized and evaluated as potential imaging agents for PR-positiv e human breast tumours. Two compounds (E- and Z-17-hydroxy-21-iodo-19- nor-17 alpha-pregna-4,20-dien-3-one; E- and Z-IPG1) were previously de scribed, but are re-evaluated. The other three were novel compounds: t wo nortestosterone analogues derived from ORG 3236 (E- and hyl-17-hydr oxy-21-iodo-11-methylene-18,19-dinor-17 alpha-pregna-4,20-diene-3-one; E- and Z-IPG2) and one norprogesterone analogue derived from ORG 2058 (21-[4-iodophenoxy]-16 alpha-ethyl-19-norpregn-4-ene-3,20-dione; IPG3 ). The E-iodovinyl nortestosterone compounds were obtained by a new ro ute of synthesis. Competitive binding studies were performed to determ ine their binding affinities for the PR in three types of tissue (huma n MCF-7 breast tumour cells and rat uterine and mammary tumour tissue) and for the androgen receptor (AR) in human MCF-7 breast tumour cells , as well as for the sex hormone-binding globulin (SHBG) and corticost eroid-binding globulin (CBG) in human plasma. All four 17 alpha-iodovi nyl nortestosterone derivatives displayed high binding affinity for th e human PR, that of Z-IPG1 and E- and Z-IPG2 being even higher than th at of ORG2058. Their affinities for the rat PR were somewhat lower, es pecially those of both E-isomers. The affinity of IPG3 was lower for b oth the human and rat PR. The nortestosterone derivatives also showed AR binding, the relative binding affinities ranging from 4.3 to 17.0% as compared with 5 alpha DHT. Additionally, neither of these steroids displayed any significant binding to either SHBG or CBG in human plasm a. We conclude that the in vitro binding properties of all four 17 alp ha-iodovinyl nortestosterone derivatives warrant evaluation of the dis tribution characteristics of their I-123-labelled analogues to determi ne their usefulness as PR imaging agents. NUCL MED BIOL 25;8:781-789, 1998. (C) 1998 Elsevier Science Inc.