RAPID VASCULAR ESCAPE OF ARTERIALLY INJECTED 16ALPHA-RADIOIODO,17BETA-ESTRADIOL

Purpose: We undertook this study because confirmation of a rapid vascu lar escape and slow release back into the circulatory system suggests that arterial injection of radiohalogenated steroid receptor ligands m ight provide an efficacious route of administration for imaging or tre atment of receptor-rich malignant tumors in peripheral tissues. Method s and Materials: We injected radiolabeled 16alpha-iodo,17beta-estradio l ([I]-E), an estrogen receptor ligand, into the femoral artery of swi ne in a solution that contained [I-125]-E in a known ratio to [Tc-99m] -labeled red blood cells. Fractions of femoral venous blood were colle cted at short intervals during 10 min. We looked for changes in the ra tio of the radiolabels. [Tc-99m]-labeled red blood cells are known to remain in the vascular system for an hour or more. Results: After pass age of the injectate through the capillary bed of the swine leg, a dra matic decrease of the initial I-125:Tc-99m ratio to only 10% was obser ved in the femoral venous blood. This ratio increased gradually during the next 10 min to approximately 30% of that in the injectate, indica ting that a significant portion (approximately 90%) of the [I-125]-E w as initially trapped in the limb and then slowly re-entered the vascul ar system. To obtain visual confirmation of the rapid vascular escape of iodo-estrogen, we injected either an imageable form of [I]-E (I-123 ]-E) or [Tc-99m]-labeled red blood cells into the dorsal aorta of supe rovulated rabbits, whose smaller size allowed whole-body imaging. The biodistributions of these radiopharmaceuticals were surveyed continuou sly by real-time planar gamma imaging. Within 2 min after the injectio n of [I-123]-E, the outlines of the circulatory system were entirely l ost; however, some estrogen receptor-rich tissues (the ovaries) as wel l as some non-target tissues, for example, the lower leg extremities, yielded well-defined images. In contrast, after intra-arterial injecti on of [Tc-99m]-labeled red blood cells, the circulatory system remaine d sharply defined for the duration of the study (40 min). Conclusion: 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 re ceptor content of the tissue.