Development of kit formulations for 99mTcN‐MPO: a cationic radiotracer for myocardial perfusion imaging

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.