Evaluation of 99 mTcN-MPO as a New Myocardial Perfusion Imaging Agent in Normal Dogs and in an Acute Myocardial Infarction Canine Model: Comparison with 99 mTc-Sestamibi

Abstract

(99) (m)TcN-MPO ([(99) (m)TcN(mpo)(PNP5)](+): mpo = 2-mercaptopyridine oxide and PNP5 = N-ethoxyethyl-N,N-bis[2-(bis(3-methoxypropyl)phosphino)ethyl]amine) is a cationic (99) (m)Tc-nitrido complex, which has favorable biodistribution and myocardial uptake with rapid liver clearance in Sprague Dawley rats. The objective of this study was to compare the biodistribution and pharmacokinetics of (99) (m)TcN-MPO and (99) (m)Tc-Sestamibi in normal dogs, and to evaluate the potential of (99) (m)TcN-MPO as a myocardial perfusion agent in canines with acute myocardial infarction. Five normal mongrel dogs were injected intravenously with (99) (m)TcN-MPO. Venous blood samples were collected via a femoral vein catheter at 0.5, 1, 2, 3, 4, 5, 10, 20, 30, 40, 60, and 90 min post-injection (p.i.). Anterior-posterior planar images were acquired by γ-camera at 10, 20, 30, 60, 90, and 120 min p.i. Regions of interest (ROIs) were drawn around the heart, liver, and lungs. The heart/liver and heart/lung ratios were calculated by dividing the mean counts in heart ROI by the mean counts in the liver and lung ROI, respectively. For comparison, (99) (m)Tc-sestamibi was also evaluated in the same five dogs. The interval period between the two examinations was 1 week to eliminate possible interference between these two radiotracers. In addition, single positron emission computed tomography (SPECT) images in the canine infarct model were collected 24 h after myocardial infarction at 30 and 60 min after the administration of (99) (m)TcN-MPO (n = 4) or (99) (m)Tc-Sestamibi (n = 4). It was found that (99) (m)TcN-MPO and (99) (m)Tc-Sestamibi displayed very similar blood clearance characteristics during the first 90 min p.i. Both (99) (m)TcN-MPO and (99) (m)Tc-Sestamibi had a rapid blood clearance with less than 50% of initial radioactivity remaining at 1 min and less than 5% at 30 min p.i. (99) (m)TcN-MPO and (99) (m)Tc-Sestamibi both showed good heart/lung contrast. The heart/liver ratio of (99) (m)TcN-MPO increased with time (0.53 ± 0.06 at 10 min, 0.90 ± 0.062 at 30 min, and 1.22 ± 0.06 at 60 min p.i.), whereas the heart/liver ratio of (99) (m)Tc-Sestamibi remained low at all time points (0.50 ± 0.03 at 10 min, 0.64 ± 0.03 at 30 min, and 0.60 ± 0.02 at 60 min p.i.). SPECT imaging studies in canines with acute myocardial infarction indicated that good visualization of the left ventricular wall and perfusion defects could be achieved at 30 min after administration of (99) (m)TcN-MPO but not after (99) (m)Tc-Sestamibi. The combination of reasonable heart uptake with rapid hepatobiliary excretion makes (99) (m)TcN-MPO a promising new radiotracer for myocardial perfusion imaging.