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