COMPARISONS OF RADIOIODOESTRADIOL BLOOD-TISSUE EXCHANGE AFTER INTRAVENOUS OR INTRAARTERIAL INJECTION

Purpose: Our study determines and compares how the major organs of lar ge 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 bec ause they affect decisions for how to optimize delivery of radiohaloge nated sex steroid receptor ligands for purposes of medical imaging and modes of radiotherapy. Methods and Materials: We used an indicator di lution technique that allows monitoring of blood-tissue exchange of ra dioactivity 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]-16alpha-iodo-17beta-estradiol ([I- 125]E) to be extracted from the blood perfusing the lung in the initia l transit after i.v. injection in vivo. Similar outcome was observed f or most major organs, including the CNS, intestines, spleen, periphera l appendages, and kidneys after i.a. injection of [I-125]E in vivo. Ho wever, within minutes the organs released the [I-125]E in its original chemical form back into the vascular system, with the exception of es trogen receptor (ER) rich tissues and the kidneys that retained the [I -125]E in its original form, although in the kidneys a nonpolar metabo lite also accumulated. Conclusion: Our experiments confirm in a large animal model that radioiodoestradiol can be sequestered or concentrate d in ER-rich sites. The liver and sex steroid receptor-rich organs mod ify considerably, by metabolism and sequestration, respectively, the a cute distribution of bioactive steroids, Our data indicate potential f or detection of ER in vivo in hormone-sensitive tumors, that is, in br east and endometrial cancers, and offer improved understanding of the recent studies in subjects with breast cancer that demonstrated that r eceptor imaging in vivo of steroid receptors with high-affinity radiol abeled ligands is possible in a clinical setting.