Development of kit formulations for 99mTcN-MPO: A cationic radiotracer for myocardial perfusion imaging

Abstract

The objective of this study was to develop a kit formulation for [ 99mTcN(mpo)(PNP5)]+ (MPO = 2-mercaptopyridine oxide), (99mTcN-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 99mTcN-MPO. We found that the most important factor affecting the RCP of 99mTcN-MPO was the purity of PNP5. 99mTcN-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 99mTcN-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 99mTc-labeling and high RCP of 99mTcN-MPO, the non-SnCl2 single-vial formulation is an attractive choice for future clinical studies. Copyright © 2014 John Wiley & Sons, Ltd.