^99mTc(CO)₃(NTA) and ¹³¹I-OIH: Comparable Plasma Clearances in Patients with Chronic Kidney Disease

Abstract

The pharmacokinetics of the tricarbonyl core radiopharmaceutical 99mTc(CO)3-nitrilotriacetic acid (99mTc(CO)3(NTA)) in rats and subjects with normal renal function are comparable to those of 131I-o-iodohippuran (131I-OIH), the radiopharmaceutical gold standard for the measurement of effective renal plasma flow. Our objective was to compare the pharmacokinetics of these 2 tracers in subjects with renal failure. Methods 99mTc (CO)3(NTA) was prepared with commercially available NTA and a commercially available labeling kit and isolated by reversed-phase high-performance liquid chromatography. Approximately 74 MBq (2.0 mCi) of 99mTc(CO)3(NTA) were coinjected with approximately 11.1 MBq (300 µCi) of 131I-OIH in 8 subjects with stage 3–4 renal failure; simultaneous images were obtained for 24 min, followed by an anterior image over the gallbladder and abdomen. Plasma clearances were determined from 10 blood samples obtained 3–180 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 99mTc(CO)3(NTA) and 131I-OIH (177 ± 63 vs. 171 ± 66 mL/min/1.73 m2, respectively) (P = 0.41). The plasma protein binding and red cell uptake of 99mTc(CO)3(NTA) were 35% ± 7% and 6% ± 3%, respectively; both values were significantly lower than the plasma protein binding (71% ± 5%) and red cell uptake (16% ± 2%) of 131I-OIH (P < 0.001). There was no significant difference in the percentage injected dose in the urine at 30 min (P = 0.24) and at 3 h (P = 0.82); for comparison, the percentage dose in the urine at 3 h was 77% ± 9% for 99mTc(CO)3(NTA) and 78% ± 11% for 131I-OIH. Image quality with 99mTc(CO)3(NTA) was excellent and no activity was identified in the gallbladder or intestine. Conclusion Results in patients with renal failure show the clearance and rate of urine excretion of 99mTc(CO)3(NTA) to be equivalent to that of 131I-OIH.

Radionuclides in Nephrourology, Part 1: Radiopharmaceuticals, Quality Control, and Quantitative Indices

“…2) (24,25). On the basis of its structure and charge distribution, 99m Tc-(CO 3 )NTA is likely to be transported by the organic anion transporter 1.…”

“…On the basis of its structure and charge distribution, 99m Tc-(CO 3 )NTA is likely to be transported by the organic anion transporter 1. Unlike 99m Tc-MAG3, however, preliminary studies in patients with chronic kidney disease show no evidence of gallbladder or gut activity (18–21,25). At the time of writing (2013), 99m Tc-(CO 3 )NTA is still under investigation and is not commercially available.…”

Monoanionic 99m Tc-tricarbonyl-aminopolycarboxylate complexes with uncharged pendant groups: Radiosynthesis and evaluation as potential renal tubular tracers

“…These three 99m Tc-tricarbonyl tracers have a negatively charged inner coordination sphere and a dianionic overall charge at physiological pH [24, 28, 29]; in addition, they also contain the free carboxylate group found in 99m Tc-MAG3, 99m Tc-EC and 99m Tc-MAEC and the other 99m Tc V O renal tracers. Furthermore, 99m Tc(CO) 3 (NTA) has been shown to have pharmacokinetic properties comparable to those of 131 I-OIH in normal volunteers [30] and also in patients with severely reduced renal function [31]. …”

Complexes Possessing Rare “Tertiary” Sulfonamide Nitrogen-to-Metal Bonds of Normal Length: fac-[Re(CO)3(N(SO2R)dien)]PF6 Complexes with Hydrophilic Sulfonamide Ligands

“…Many fac -[ 99m Tc(CO) 3 L] n imaging agents with facially coordinated tridentate ligands (L) have been studied 1-8 because of the convenient generation of the fac -[ 99m Tc(CO) 3 (H 2 O) 3 ] + precursor. 9,10 Some of these imaging agents have exhibited satisfactory results in human volunteers and in early patient studies.…”

“…9,10 Some of these imaging agents have exhibited satisfactory results in human volunteers and in early patient studies. 4,7,8 Such fac -[ 99m Tc(CO) 3 L] n agents are more robust and have better pharmacokinetic properties than agents with bidentate ligands. 11 The γ -emitting 99m Tc radionuclide has ideal nuclear properties 12,13 for diagnostic applications in nuclear medicine.…”