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Comparison of Technetium-99m MAG₃ Kit with HPLC-Purified Technetium-99m MAG₃ and OIH in Rats

Pharmacology and Toxicology Research, Mallinckrodt, Inc.; Hazelwood, Missouri

Correspondence: For reprints contact: Joseph R. Coveney, PhD, Mallinckrodt, Inc., 675 McDonnell Blvd., Hazelwood, MO 63042.

ABSTRACT

Technetium-99m (^99mTc) mercaptoacetylglycylglycylglycine (MAG₃) in high (95%) radiochemical purity is prepared from lyophilized kits containing benzoylMAG₃, sodium tartrate, lactose, and stannous chloride by adding sodium [^99mTc]pertechnetate and heating the contents briefly. Constant-infusion renal whole-blood clearance obtained with [^99mTc] MAG₃, kits was compared with that obtained with high performance liquid chromatography (HPLC) pure [^99mTc]MAG₃ and with co-infused iodine-131(¹³¹I)iodohippurate (OIH) in anesthetized rats. Average renal whole-blood clearance of [^99mTc]MAG₃ from kits was 3.9 ± 0.4 ml/min/100 g body weight (mean ± s.e.m. n = 5) and that for HPLC-pure [^99mTc]MAG₃ was 4.6 ± 0.3 (n = 3). Renal whole-blood clearance ratios for [^99mTc]MAG₃ to co-infused iodine-131(¹³¹I) OIH were greater than unity for both kit formulation (1.7 ± 0.1) and HPLC-pure [^99mTc]MAG₃ (1.9 ± 0.2). Differences in these two measures were not significant. Plasma binding (determined from blood drawn at the end of the infusion) of [^99mTc]MAG₃ prepared from both kits (75 ± 2%, n = 4) and HPLC-separation (76 ± 4%) were greater than that of [¹³¹I]OIH in corresponding plasma samples (31 ± 1% and 32 ± 2%, respectively). Renograms performed in anesthetized rats revealed no statistically significant differences between kit prepared [^99mTc]MAG₃ and [¹³¹I]OIH in terms of time-to-peak renal activity (5.0 ± 1.7 min, n = 6; and 2.2 ± 0.2 min, n = 3, mean ± s.e.m. for [^99mTc]MAG₃ and [¹³¹I]OIH, respectively), in terms of time to fall to half-maximal activity (15.3 ± 2.4 min and 9.6 ± 2.1 min, respectively), or in terms of fraction of peak radioactivity in right kidney (0.53 ± 0.01 for both substances). To assess possible interference from hepatobiliary uptake and excretion in renal failure, radioactivity in liver regions of interest was followed by gamma camera scintigraphy for 30 min after intravenous injection of [¹³¹I]OIH and kit and HPLC-purified [^99mTc]MAG₃, in anesthetized rats rendered anephric by ligating renal peduncles. Liver activity was 25% of total for both preparations of [^99mTc]MAG₃ and was 22% of total for [¹³¹I]OIH. There were no significant differences among the substances.