Development of kit formulations for (99m) TcN-MPO: a cationic radiotracer for myocardial perfusion imaging

J Labelled Comp Radiopharm. 2014 Jul;57(9):584-92. doi: 10.1002/jlcr.3221. Epub 2014 Jul 28.


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.

Keywords: 99mTcN-MPO; formulation development; myocardial perfusion imaging; radiotracers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclodextrins / chemistry
  • Drug Compounding
  • Drug Packaging
  • Drug Stability
  • Myocardial Perfusion Imaging
  • Organotechnetium Compounds / chemical synthesis
  • Organotechnetium Compounds / chemistry*
  • Organotechnetium Compounds / pharmacokinetics
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / chemistry*
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Reagent Kits, Diagnostic*
  • Tin Compounds / chemistry
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon


  • Cyclodextrins
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • Reagent Kits, Diagnostic
  • Tin Compounds
  • technetium 99m (2-mercaptopyridine N-oxide)(N-ethoxyethyl-N,N-bis(2-(bis(3-methoxypropyl)phosphino)ethyl)amine)