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-[Tc-99m(I)(CO)(3)(NTA)](2-) Diagnostic Renal Agent

• Type of Material: Article
• Authors: Jeffrey Klenc, Emory University; Malgorzata Lipowska, Emory University; Pramuditha L. Abhayawardhana, Louisiana State University; Andrew Taylor Jr., Emory University; Luigi G. Marzilli, Louisiana State University
• Language: English
• Date: 2015-07-06
• Publisher: American Chemical Society
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 American Chemical Society.
• Final Published Version (URL): http://dx.doi.org/10.1021/acs.inorgchem.5b00584
• Title of Journal or Parent Work: Inorganic Chemistry
• ISSN: 0020-1669
• Volume: 54
• Issue: 13
• Start Page: 6281
• End Page: 6290
• Grant/Funding Information: This work was supported by the National Institute of Health/National Institute of Diabetes and Digestive and Kidney Diseases (Grant No. R37 DK038842).
• Keywords: Physical Sciences; IMAGING AGENTS; OXO COMPLEXES; SOLID-STATE; COMPLEXES RELEVANT; AQUEOUS-SOLUTION; CHELATE LIGANDS; Chemistry, Inorganic & Nuclear; TRIDENTATE LIGANDS; Chemistry; KIDNEY-FUNCTION; TC-99M; Science & Technology; X-RAY
• Research Categories: Health Sciences, General; Chemistry, Inorganic

Abstract

We previously identified two new agents based on the [99mTcVO]3+ core with renal clearances in human volunteers 30% higher than that of the widely used clinical tracer 99mTc-MAG3 (MAG35− = penta-anion of mercaptoacetyltriglycine). However, renal agents with even higher clearances are needed. More recently, we changed our focus from the [99mTcVO]3+ core to the discovery of superior tracers based on the fac-[99mTcI(CO)3]+ core. Compared to 99mTc-MAG3, fac-[99mTcI(CO)3(NTA)]2− (NTA3− = tri-anion 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-[ReI(CO)3(NTA)]2− with a –CH2CO2− dangling monoanionic chain and on two fac-[ReI(CO)3(L)]− analogs with either a –CH2CONH2 or –CH2CH2OH dangling neutral chain. In these three fac-[ReI(CO)3(L)]n− complexes, the fac-[ReI(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-[99mTcI(CO)3(L)]− analogs with these neutral dangling chains were found to have pharmacokinetic properties very closely similar to those of fac-[99mTcI(CO)3(NTA)]2−. Therefore, we reach the unexpected conclusion that in fac-[99mTcI(CO)3(L)]n− agents, renal clearance is affected much more than anticipated by features of the core plus the chelate rings (the [99mTcI(CO)3(N(CH2CO2)2)]− moiety) than by the presence of a negatively charged dangling carboxylate chain.