(99m)Tc(CO)3(NTA): a (99m)Tc renal tracer with pharmacokinetic properties comparable to those of (131)I-OIH in healthy volunteers

Abstract

Studies in rats showed that the pharmacokinetics of the tricarbonyl core radiopharmaceutical (99m)Tc(CO)(3)-nitrilotriacetic acid, (99m)Tc(CO)(3)(NTA), were essentially identical to those of (131)I ortho-iodohippuran ((131)I-OIH), the clinical gold standard for the measurement of effective renal plasma flow. Our objective was to compare the pharmacokinetics of these 2 tracers in healthy volunteers.

Methods: (99m)Tc(CO)(3)(NTA) was prepared with commercially available NTA and a commercially available kit and isolated by reversed-phase high-performance liquid chromatography. Approximately 74 MBq (2 mCi) of (99m)Tc(CO)(3)(NTA) were coinjected with 9.25 MBq (250 microCi) of (131)I-OIH in 9 volunteers, and simultaneous imaging of each tracer was performed for 24 min. Plasma clearances were determined from 8 blood samples obtained 3-90 min after injection using the single-injection, 2-compartment model. Plasma protein binding, red cell uptake, and percentage injected dose in the urine at 30 and 180 min were determined.

Results: There was no difference in the plasma clearances of (99m)Tc(CO)(3)(NTA) and (131)I-OIH, 475 +/- 105 mL/min versus 472 +/- 108 mL/min, respectively. The plasma protein binding and red cell uptake of (99m)Tc(CO)(3)(NTA) were 43% +/- 5% and 9% +/- 6%, respectively; both values were significantly lower (P < 0.001) than the plasma protein binding (75% +/- 3%) and red cell uptake (17% +/- 5%) of (131)I-OIH. There was no significant difference in the percentage injected dose recovered in the urine at 30 min and at 3 h; for comparison, the percentage dose in the urine at 3 h was 91% +/- 4% for (99m)Tc(CO)(3)(NTA) and 91% +/- 6% for (131)I-OIH (P = 0.96). Image quality with (99m)Tc(CO)(3)(NTA) was excellent, and the renogram parameters were similar to those of (131)I-OIH.

Conclusion: Preliminary results in healthy volunteers suggest that the pharmacokinetic behavior of (99m)Tc(CO)(3)(NTA) is comparable to that of (131)I-OIH.

Figure 1

Bar graphs comparing the clearance (A), plasma protein binding (PPB) (B) and red cell uptake (RBC) (C) of ^99mTc(CO)₃(NTA) and ¹³¹I-OIH in healthy volunteers.

Figure 2

Bar graphs comparing the urine excretion of ^99mTc(CO)₃(NTA) and ¹³¹I-OIH at 30 and 180 min in healthy volunteers.

Figure 3

A urine sample from healthy volunteer injected with ^99mTc(CO)₃(NTA) was subjected to reversed-phase HPLC analysis (A) and compared to a reference HPLC ^99mTc(CO)₃(NTA) tracing (B). Both tracings show single peak with same retention times indicating that ^99mTc(CO)₃(NTA) is excreted unchanged in urine.

Figure 4

Two-minute kidney images after simultaneous injection of 79.2 MBq (2.14 mCi) of ^99mTc(CO)₃(NTA) (A) and 8.9 MBq (240 uCi) of ¹³¹I-OIH (B) in a healthy 22-y-old female volunteer. Whole-kidney and cortical (parenchymal) renogram curves are displayed in C for ^99mTc(CO)₃(NTA)andin D for ¹³¹I-OIH. Renogram curves for ¹³¹I-OIH are quite noisy because of relatively low count rate resulting from a lower administered dose and the poor capture of the 364-keV photon of I-131 by 9.5 mm (3/8 in) crystal.

Figure 5

Camera-based clearance (mL/min/1.73 m²) for ^99mTc(CO)₃(NTA) and ^99mTc-MAG3.