454
Antitumor Steroids
ER-positive cells (as for antiestrogens) but
also to ER-negative cells located in their
neighborhood.
4.2.1
123
Iand
125
I Labeled Compounds
Several [
125
I] labeled E
2
derivatives have
been synthesized for
in vivo
imaging of
ER-positive tumors. Utility of this ap-
proach in cancer diagnostic has, however,
never been demonstrated. Nevertheless,
biodistribution as well as imaging in-
vestigations performed on both animals
and humans suggest some uptake selec-
tivity, especially for 17
α
-iodovinyl deriva-
tives. Stereochemistry of such compounds
appears
of
prime
importance
for
ER
binding;
Z
-isomers bind more effectively
than corresponding
E
-isomers. These data
conFrm the concept that the HBD pos-
sesses a hydrophobic subsite able to accept
lipophilic moieties linked in position 17
α
of E
2
(see Sect. 3.1.4). In an effort to utilize
this concept, a series of 17
α
-substituted
E
2
derivatives were synthesized, four of
them bearing iodine-123 (±ig. 9). The bind-
ing of these four compounds depends on
the nature of their substituents with an
alkene linkage being greatly preferred over
alkynyl and alkyl. Preference for the
Z
-
alkene geometry conFrms the conclusion
from studies on parent iodovinyls. Addi-
tional biodistribution studies performed
with the
Z
-alkene suggested some uptake
selectivity (uterus/ovary) and metabolic
instability (accumulation of free iodine
within the thyroid).
16
α
-[
125
I]iodo-estradiol has been shown
to
produce
a
receptor-mediated
cyto-
toxicity on MC±-7 breast cancer cells.
The decrease of survival rate provoked
HO
H
H
125
I
HO
E-isomer
HO
H
125
I
HO
Z-isomer
H
HO
Y
I
123
OH
Y
=
(Z) CH
CH
Y
=
(E) CH
CH
Y
=
CH
2
CH
2
Y
=
C
C(CH
2
)
3
OH
125
I
HO
Fig. 9
Radiolabeled E
2
derivatives. Chemical formulas of iodinated
(
123
Iand
125
I) derivatives described in Sect. 4.2.1.
