^99mTc(CO)₃(NTA): A ^99mTc Renal Tracer with Pharmacokinetic Properties Comparable to Those of ¹³¹I-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 mCi) 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 6 105 mL/min versus 472 6 108 mL/min, respectively. The plasma protein binding and red cell uptake of 99m Tc(CO) 3 (NTA) were 43% 6 5% and 9% 6 6%, respectively; both values were significantly lower (P , 0.001) than the plasma protein binding (75% 6 3%) and red cell uptake (17% 6 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% 6 4% for 99m Tc(CO) 3 (NTA) and 91% 6 6% for 131 I-OIH (P 5 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.Key Words: 99m Tc-tricarbonyl; renal radiopharmaceuticals; 99m Tc(CO) 3 (NTA); 131 I-ortho-iodohippuran ( 131 I-OIH); 99m Tc-mercaptoacetyltriglycine ( 99m

Iminoether Complexes of the Type, fac‐[Re(CO)3L{HNC(CH3)OCH3}]BF4 (L = Bipyridine or a Substituted Bipyridine): Synthesis and Properties

“…[38] This relationship of a decrease in the θ P with an increase in the M-N length is most evident (Tables 2 and 3) when the θ P of the other complexes in this study (all of which have very similar Re-N lengths) are compared with the θ P for [Re(CO) 3 (6,6Ј-Me 2 bipy){HNC(CH 3 )OCH 3 }]BF 4 , which has slightly longer Re-N lengths and the smallest θ P value (4.0°).…”

“…[34,39] For the alkyl acetimidate complexes, the Re-N bond lengths varied from 2.1706 (17) 4 , in which the Re-N bond lengths are about 2.21 Å (as discussed above).…”

“…Therefore, in order to overcome the above mentioned aqueous chemistry problems, we evaluated the use in the distortion of L and the methyl substituent position have little influence on the ease of iminoether formation. However, a higher steric bulk of the alcohol (methanol, ethanol, and 2-propanol) decreases the ease of fac-[Re(CO) 3 (5,5Ј-Me 2 bipy){HNC(CH 3 )OR}]BF 4 formation. Isopropanol did not form the iminoether complex after two days of heating the reaction mixture at reflux.…”

“…[1][2][3] This approach has led to the development of fac-{ 99m Tc(CO) 3 } + renal agents that have shown promising pharmacokinetic properties in humans. [4,5] We have noted that there are some problems in utilizing water, which is the solvent that is used to prepare the common precursor, fac-[Re(CO) 3 (H 2 O) 3 ] + . [1] In water, the various pH conditions lead to different linkage isomers or mixtures of isomers for the complicated ligands.…”

Synthesis and In Vivo Evaluation ofp-18F-Fluorohippurate as a New Radiopharmaceutical for Assessment of Renal Function by PET

“…One of the goals in the radiopharmaceutics of renal agents has been to closely mimic the most original compound. For example, recently Taylor et al have developed a new renal agent, 99m Tc(CO) 3 (NTA), which demonstrated pharmacokinetic properties and renogram parameters essentially identical to those of 131 I-OIH in healthy humans (27). The structural and functional similarity of 131 I-OIH to PAH made 131 I-OIH the imaging gold standard for tubular function assessment.…”