Rapid vascular escape of arterially injected 16 alpha-radioiodo,17 beta-estradiol

We undertook this study because confirmation of a rapid vascular escape and slow release back into the circulatory system suggests that arterial injection of radiohalogenated steroid receptor ligands might provide an efficacious route of administration for imaging or treatment of receptor-rich malignant tumors in peripheral tissues.

We injected radiolabeled 16 alpha-iodo,17 beta-estradiol ([I]-E), an estrogen receptor ligand, into the femoral artery of swine in a solution that contained [125I]-E in a known ratio to [99mTc]-labeled red blood cells. Fractions of femoral venous blood were collected at short intervals during 10 min. We looked for changes in the ratio of the radiolabels. [99mTc]-labeled red blood cells are known to remain in the vascular system for an hour or more.

After passage of the injectate through the capillary bed of the swine leg, a dramatic decrease of the initial 125I:99mTc ratio to only 10% was observed in the femoral venous blood. This ratio increased gradually during the next 10 min to approximately 30% of that in the injectate, indicating that a significant portion (approximately 90%) of the [125I]-E was initially trapped in the limb and then slowly re-entered the vascular system. To obtain visual confirmation of the rapid vascular escape of iodo-estrogen, we injected either an imageable form of [I]-E (123I]-E) or [99mTc]-labeled red blood cells into the dorsal aorta of superovulated rabbits, whose smaller size allowed whole-body imaging. The biodistributions of these radiopharmaceuticals were surveyed continuously by real-time planar gamma imaging. Within 2 min after the injection of [123I]-E, the outlines of the circulatory system were entirely lost; however, some estrogen receptor-rich tissues (the ovaries) as well as some non-target tissues, for example, the lower leg extremities, yielded well-defined images. In contrast, after intra-arterial injection of [99mTc]-labeled red blood cells, the circulatory system remained sharply defined for the duration of the study (40 min).

A large fraction of [I]-E escapes from the vascular system during the first pass through an organ or limb, without regard to the estrogen receptor content of the tissue.