An Experimental Study Of ⁹⁹Tc^m-MPO For Early Myocardial Perfusion Imaging

Objectives:To Study ⁹⁹Tc^m-MPO（[99mTc N（MPO）（PNP5）+: 2-mercapto pyridine N-oxide and N-ethoxy ethyl-N, N-two [2（two（3-methoxy propyl） phosphine） ethyl] amine） biodistribution in normal mice. To study the biodistribution in vivo and its application as a new myocardial perfusion imaging tracer on the clinical application value..Methods:1)⁹⁹Tc^m-MPO was synthesized in two steps, and using HPLC method to analyze the radiolabeling rate and in vitro stability of ⁹⁹Tc^m-MPO. The normal Kunming rats injection of ⁹⁹Tc^m–MPO 3.7 MBq via tail vein, the biodistribution（%ID/g） in dissected organs were measured respectively at 5, 15, 30, 60 and 120 min post-injection（p.i.）.2) New Zealand rabbits were intravenously injected with ⁹⁹Tc^m-MPO,99 TcmTetrofosmin and ⁹⁹Tc^m-MIBI 37 MBq, and static images were performed by SPECT at 5min, 15 min, 30 min, 60 min p.i.,respectively.3)Proceed SPECT/CT imaging respectively at 15 and 60 min p.i. after blocking blood flow with a balloon in the experimental miniature pigs’ coronary artery left circumflex branch.Results1)⁹⁹Tc^m-MPO had high radiolabeling yield of（98.8±1.0）%and stability.2)In vivo biodistribution study demonstrated that uptake of ⁹⁹Tc^m-MPO in the kidneys was similar to ⁹⁹Tc^m-tetrofosmin at 5 min p.i.,The uptake of ⁹⁹Tc^m-MPO in liver was（30.38±0.43）%ID/g at 5min, slightly more than 99 Tcm-MIBI and 99 Tcmtetrofosmin, but ⁹⁹Tc^m-MPO has a faster liver clearance.The uptake of ⁹⁹Tc^m-MPO in the heart was（9.38±0.70）%ID/g at 15 min p.i., slightly lower than 99 Tcm-MIBI and ⁹⁹Tc^m-tetrofosmin,but there was no statistically significant difference.The factor that ⁹⁹Tc^m-MPO has a significantly higher heart/liver ratios than 99 Tcm-MIBI and 99 Tcmtetrofosmin at 15 min p.i.(heart/liver ratios:2.21±0.44 vs 0.62±0.02 for 99 Tcm-MIBI and 0.89±0.06 for ⁹⁹Tc^m-tetrofosmin).3)New Zealand rabbits planar imaging after intravenous injection ⁹⁹Tc^m-MPO showed visible images of the heart and liver at 5min p.i.,and the radioactivity uptake in liver significantly reduced at 15 min p.i.. ⁹⁹Tc^m-MPO has higher heart-liver ratios than 99 Tcm-MIBI and ⁹⁹Tc^m-tetrofosmin at 15 min p.i.(heart-liver ratios0.85±0.32 vs 0.71±0.15 for 99 Tcm-MIBI and 0.59±0.64 for ⁹⁹Tc^m-tetrofosmin), but there was no statistically significant difference.4)SPECT showed decreased uptake of ⁹⁹Tc^m-MPO by lesions with ischemia and reperfusion injury in porcine models.Conclusions1)⁹⁹Tc^m-MPO is a new myocardial perfusion imaging tracer. Comparable with ⁹⁹Tc^m-MIBI,⁹⁹Tc^m-MPO showed higher uptake in heart, longer myocardial radioactivity retention time,and quicker liver clearance.The heart-liver radioactivity uptake was higher than ⁹⁹Tc^m-MIBI and ⁹⁹Tc^m-tetrofosmin at 15 min p.i..2)⁹⁹Tc^m–MPO may be used for early myocardial ischemia perfusion imaging, and has a good prospect of clinical application.