Effects of altered physiologic states on clearance and biodistribution of technetium-99m MAG3, iodine-131 OIH, and iodine-125 iothalamate

Abstract

Technetium-99m mercaptoacetyltriglycine [( 99mTc]MAG3) is a new renal radiopharmaceutical with biologic properties similar to iodine-131 orthoiodohippuric acid [( 131I]OIH). MAG3 may be used as a replacement for [131I]OIH and/or [99mTc]DTPA. For this reason, we compared the effects of several potential adverse clinical conditions on the clearance and biodistribution of MAG3, OIH and a GFR marker. To simulate renal failure, five mice underwent bilateral renal pedical ligation. Twenty-four hours after surgery they were injected with MAG3 and OIH and killed 2 hr postinjection. Compared to sham operated controls, liver activity for MAG3 and OIH increased from 0.2% to 14.1% and 0.1% to 13.9%, respectively, while intestinal activity increased from 1.3% to 8.9% for MAG3 and 0.2% to 7.7% for OIH. Constant infusion studies were performed in rats to evaluate the effects of increased plasma organic acid levels, mannitol diuresis, dehydration, and acid/base imbalance on the clearance of OIH, MAG3, and [125I]iothalamate. No differences were noted between the OIH and MAG3 clearances following diuresis and dehydration and the differences involving acid/base imbalance were minimal. Dehydration depressed the clearance of [125I]iothalamate more than that of OIH or MAG3. Para-aminohippurate (PAH) infusion inhibited the clearance of MAG3 more than OIH supporting proximal tubular transport for MAG3; PAH had no effect on [125I]iothalamate. In summary HPLC purified MAG3 behaved similarly to OIH under adverse physiologic conditions and the data continue to support the use of MAG3 as a potential clinical substitute for OIH.