Comparisons of radioiodoestradiol blood-tissue exchange after intravenous or intraarterial injection.
OBJECTIVE
Our study determines and compares how the major organs of large animals handle exogenous halogenated bioactive sex steroids within the first minutes after their i.v. or i.a. injection. The rationale is that an understanding is needed of the acute physiological events because they affect decisions for how to optimize delivery of radiohalogenated sex steroid receptor ligands for purposes of medical imaging and modes of radiotherapy.


METHODS
We used an indicator dilution technique that allows monitoring of blood-tissue exchange of radioactivity in a continuous manner in anesthetized surgically prepared swine.


RESULTS
In swine, with by-passed liver circulation, the lungs allow the vast majority of [I-125]-16 alpha-iodo-17 beta-estradiol ([I-125]E) to be extracted from the blood perfusing the lung in the initial transit after i.v. injection in vivo. Similar outcome was observed for most major organs, including the CNS, intestines, spleen, peripheral appendages, and kidneys after i.a. injection of [I-125]E in vivo. However, within minutes the organs released the [I-125]E in its original chemical form back into the vascular system, with the exception of estrogen receptor (ER) rich tissues and the kidneys that retained the [I-125]E in its original form, although in the kidneys a nonpolar metabolite also accumulated.


CONCLUSIONS
Our experiments confirm in a large animal model that radioiodoestradiol can be sequestered or concentrated in ER-rich sites. The liver and sex steroid receptor-rich organs modify considerably, by metabolism and sequestration, respectively, the acute distribution of bioactive steroids. Our data indicate potential for detection of ER in vivo in hormone-sensitive tumors, that is, in breast and endometrial cancers, and offer improved understanding of the recent studies in subjects with breast cancer that demonstrated that receptor imaging in vivo of steroid receptors with high-affinity radiolabeled ligands is possible in a clinical setting.
Scharl
A
A
Department of Obstetrics and Gynecology, University of Chicago, IL 60637-1470, USA.
Beckmann
M W
MW
Artwohl
J E
JE
Holt
J A
JA
D000818:Animals; D001921:Brain / Q000378:metabolism; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D005260:Female; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D013552:Swine; D013667:Technetium / Q000378:metabolism
D011960:Receptors, Estrogen; D004958:Estradiol; C024871:16 alpha-iodoestradiol; D013667:Technetium