Antitumor Steroids
455
by this radioligand was associated with
chromosomal
aberrations;
of
note,
an
excess of diethylstilbestrol, used as poten-
tial competitor, prevented the decrease of
survival rate as well as chromosomal aber-
rations. Despite the promising aspect of
these data, estimated residence times of
125
I-labeled estrogens in ER-positive cells
(ER half-life: less than 3 h) appear be too
low for an efFcient cell killing. In this
regard, the Auger electron-emitting nu-
cleotides such as iodine-123 that release
their energy within a short period of time
would be more powerful to selectively kill
ER-positive cells (i.e. half-life of
123
I
=
4
.
4h vs
125
I
=
60 days). Testing of 17
α
-
[
123
I]iodovinyl-11
β
methoxy-estradiol on
Chinese hamster ovary cells expressing or
not high level of ER provided credence to
this concept.
4.2.2
α
-Emitting Compounds
Auger
electron
emitter
agents
would
only affect ER-positive cells due to their
weak distance of irradiation potency.
α
-
particle emitting radionucleotides such
as astatine-211 are attractive candidates
to palliate this
gap and affect neigh-
boring ER-negative cells (range of ra-
d
i
a
t
i
o
ni
nt
i
s
s
u
ei
s1
0t
o1
0
0
µ
m);
astatine-211
can
substitute
iodine
in
many syntheses making the production
of
211
At-labeled E
2
easily feasible. In fact,
[
211
At]astatinovinylestradiol (as well as its
11
β
methoxylated derivative) has been
established. One may hope that such com-
pounds produce a cytotoxic effect as their
125
I-labeled analogs.
The possibility to generate
α
-emitting
isotopes by boron capture therapy is an-
other approach under exploration. Boron-
10,
when
irradiated
with
low
energy
thermal neutrons, yields
α
-particles and
7
Li-nuclei. The success of this therapy is
dependant on the quantity of boron-10 and
thermal neutrons to deliver to the cancer
cells to sustain an
α
-lethal radiation. Carbo-
ranes
(dicarba-closo-dodecaboranes)
are
a class of carbon-containing polyhedral-
boron clusters having remarkable thermal
stability and exceptional hydrophobic char-
acter; they have been utilized to incor-
porate a large number of boron atoms
into tumor cells. Remarkably, hydropho-
bic interactions between carboranes and
ER may occur when linked to a phe-
nol. This Fnding led to the design of
several compounds sharing high bind-
ing afFnity for the receptor as well as
estrogenic and/or antiestrogenic activity
on an ER-dependent reporter gene (i.e.
analogs of E
2
, OH-Tam or RU 39,411;
±ig. 10). One may speculate that such
drugs may play a role in cancer therapy
since they combine suitable endocrine and
radiotoxic properties.
OH
HO
HO
OCH
2
CH
2
N(CH
3
)
2
(H
3
C)
2
NCH
2
CH
2
O
HO
Fig. 10
Chemical formulas of phenolic carboranes with structural and ER binding
properties to (a) E
2
, (b) OH-Tam, and (c) RU 39,411 (Sect. 4.2.2).
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