title: Structure and Properties of fac-[Re(I)(CO)3(NTA)](2-) (NTA(3-) = Trianion of Nitrilotriacetic Acid) and fac-[Re(I)(CO)3(L)](n-) Analogues Useful for Assessing the Excellent Renal Clearance of the fac-[(99m)Tc(I)(CO)3(NTA)](2-) Diagnostic Renal Agent.
abstract: We previously identified two new agents based on the [(99m)Tc(V)O](3+) core with renal clearances in human volunteers 30% higher than that of the widely used clinical tracer (99m)Tc-MAG3 (MAG3(5-) = penta-anion of mercaptoacetyltriglycine). However, renal agents with even higher clearances are needed. More recently, we changed our focus from the [(99m)Tc(V)O](3+) core to the discovery of superior tracers based on the fac-[(99m)Tc(I)(CO)3](+) core. Compared to (99m)Tc-MAG3, fac-[(99m)Tc(I)(CO)3(NTA)](2-) (NTA(3-) = trianion of nitrilotriacetic acid) holds great promise by virtue of its efficient renal clearance via tubular secretion and the absence of hepatobiliary elimination, even in patients with severely reduced renal function. We report here NMR, molecular (X-ray) structure, and solution data on fac-[Re(I)(CO)3(NTA)](2-) with a -CH2CO2(-) dangling monoanionic chain and on two fac-[Re(I)(CO)3(L)](-) analogues with either a -CH2CONH2 or a -CH2CH2OH dangling neutral chain. In these three fac-[Re(I)(CO)3(L)](n-) complexes, the fac-[Re(I)(CO)3(N(CH2CO2)2)](-) moiety is structurally similar and has similar electronic properties (as assessed by NMR data). In reported and ongoing studies, the two fac-[(99m)Tc(I)(CO)3(L)](-) analogues with these neutral dangling chains were found to have pharmacokinetic properties very similar to those of fac-[(99m)Tc(I)(CO)3(NTA)](2-). Therefore, we reach the unexpected conclusion that in fac-[(99m)Tc(I)(CO)3(L)](n-) agents, renal clearance is affected much more than anticipated by features of the core plus the chelate rings (the [(99m)Tc(I)(CO)3(N(CH2CO2)2)](-) moiety) than by the presence of a negatively charged dangling carboxylate chain.
authors.affiliation: †Department of Radiology and Imaging Sciences, Emory University, Atlanta, Georgia 30322, United States.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Klenc
authors.affiliation: †Department of Radiology and Imaging Sciences, Emory University, Atlanta, Georgia 30322, United States.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Lipowska
authors.affiliation: ‡Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803, United States.
authors.forename: Pramuditha L
authors.initials: PL
authors.lastname: Abhayawardhana
authors.affiliation: †Department of Radiology and Imaging Sciences, Emory University, Atlanta, Georgia 30322, United States.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Taylor
authors.affiliation: ‡Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803, United States.
authors.forename: Luigi G
authors.initials: LG
authors.lastname: Marzilli
mesh_terms: D015415:Biomarkers / Q000032:analysis; D056831:Coordination Complexes / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009571:Nitrilotriacetic Acid / Q000737:chemistry*; D015609:Organotechnetium Compounds / Q000737:chemistry*; D012076:Renal Agents / Q000737:chemistry*; D012211:Rhenium / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D056831:Coordination Complexes; D015609:Organotechnetium Compounds; D012076:Renal Agents; D012211:Rhenium; D009571:Nitrilotriacetic Acid