title: Development of kit formulations for (99m) TcN-MPO: a cationic radiotracer for myocardial perfusion imaging.
abstract: The objective of this study was to develop a kit formulation for [(99m) TcN(mpo)(PNP5)](+) (MPO = 2-mercaptopyridine oxide), ((99m) TcN-MPO) to support its clinical evaluations as a SPECT radiotracer. Radiolabeling studies were performed using three different formulations (two-vial formulation and single-vial formulations with/without SnCl2 ) to explore the factors influencing radiochemical purity (RCP) of (99m) TcN-MPO. We found that the most important factor affecting the RCP of (99m) TcN-MPO was the purity of PNP5. (99m) TcN-MPO was prepared >98% RCP (n = 20) using the two-vial formulation. For single-vial formulations with/without SnCl2 , β-cyclodextrin (β-CD) is particularly useful as a stabilizer for PNP5. The RCP of (99m) TcN-MPO was 95-98% using β-CD, but its RCP was only 90-93% with γ-cyclodextrin (γ-CD). It seems that PNP5 fits better into the inner cavity of β-CD, which forms more stable inclusion complex than γ-CD in the single-vial formulations. The results from biodistribution and imaging studies in Sprague-Dawley rats clearly demonstrated biological equivalence of three different formulations. Single photon-emission computed tomography data suggested that high quality images could be obtained at 0-30-min post-injection without significant interference from the liver radioactivity. Considering the ease for (99m) Tc-labeling and high RCP of (99m) TcN-MPO, the non-SnCl2 single-vial formulation is an attractive choice for future clinical studies.
authors: School of Health Sciences, Purdue University, West Lafayette, IN, 47907, USA; Department of Nuclear Medicine, China-Japan Friendship Hospital, Beijing, 100029, China.
authors: Yumin
authors: Y
authors: Zheng
authors: Shundong
authors: S
authors: Ji
authors: Elena
authors: E
authors: Tomaselli
authors: Shuang
authors: S
authors: Liu
mesh_terms: D000818:Animals; D003505:Cyclodextrins / Q000737:chemistry; D004339:Drug Compounding; D004349:Drug Packaging; D004355:Drug Stability; D055414:Myocardial Perfusion Imaging; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011933:Reagent Kits, Diagnostic; D017971:Tin Compounds / Q000737:chemistry; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D003505:Cyclodextrins; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D011933:Reagent Kits, Diagnostic; D017971:Tin Compounds; C532955:technetium 99m (2-mercaptopyridine N-oxide)(N-ethoxyethyl-N,N-bis(2-(bis(3-methoxypropyl)phosphino)ethyl)amine)
keywords: 99mTcN-MPO; formulation development; myocardial perfusion imaging; radiotracers