Discovery Research, Lantheus Medical Imaging, 331 Treble Cove Rd., N. Billerica, MA 01862, USA.
J Nucl Cardiol. 2010 Aug;17(4):631-6. doi: 10.1007/s12350-010-9221-7. Epub 2010 Mar 26.
BMS747158 labeled with (18)F is being developed for PET myocardial perfusion imaging. Imaging studies showed clear detection of necrotic tissue in acute myocardial infarcted (MI) animals and a good safety profile in normal animals. This study evaluated BMS747158 imaging and cardiovascular safety in a rabbit model of chronic MI with cardiac compromise.
Chronic MI rabbits were developed by the left coronary artery ligation followed by 4 weeks recovery. Cardiac PET imaging with BMS747158 (~1.5 mCi, iv) in control rabbits showed clear and uniform myocardial uptake. However, imaging in chronic MI rabbits demonstrated obvious defect area in the left ventricular wall. Before BMS747158 injection, baseline electrocardiogram (ECG) waveforms in lead II configuration were normal with positive QRS complexes in control rabbits. In contrast, MI rabbits exhibited negative QRS complexes with enlarged Q waves and inverted T waves. Baseline values of mean intra-arterial pressure (AP, 61 +/- 6 vs 89 +/- 11 mmHg), systolic AP (79 +/- 11 vs 114 +/- 11 mmHg) and diastolic AP (53 +/- 4 vs 76 +/- 10 mmHg) were lower in MI than in control rabbits. Heart rate (162 +/- 36 vs 159 +/- 8 beat/minute) and QTc interval (corrected by Fridericia method, 288 +/- 17 vs 319 +/- 17 ms) were comparable. BMS747158 administration induced no changes from baseline in any of the measured cardiovascular parameters and ECG waveforms in either control or MI rabbits.
Cardiac imaging with BMS747158 allows clear detection of chronic MI without producing any cardiovascular alterations in cardiac compromised rabbits.
正在开发一种标记为 (18)F 的 BMS747158，用于 PET 心肌灌注成像。成像研究表明，在急性心肌梗死 (MI) 动物模型中可以清楚地检测到坏死组织，并且在正常动物中具有良好的安全性。本研究评估了 BMS747158 在伴有心脏损伤的慢性 MI 兔模型中的成像和心血管安全性。
通过左冠状动脉结扎后 4 周恢复，建立慢性 MI 兔模型。在对照组兔中，静脉注射 (~1.5 mCi) BMS747158 后，心脏 PET 成像显示左心室壁清晰且均匀的心肌摄取。然而，在慢性 MI 兔中，成像显示左心室壁明显缺陷区域。在注射 BMS747158 之前，对照组兔的 II 导联心电图 (ECG) 波形正常，表现为正向 QRS 复合体。相比之下，MI 兔的 QRS 复合体呈负向，Q 波增大，T 波倒置。MI 兔的平均动脉压 (AP，61 +/- 6 对 89 +/- 11 mmHg)、收缩压 AP (79 +/- 11 对 114 +/- 11 mmHg) 和舒张压 AP (53 +/- 4 对 76 +/- 10 mmHg) 的基线值低于对照组。心率 (162 +/- 36 对 159 +/- 8 次/分钟) 和 QTc 间期 (Fridericia 法校正，288 +/- 17 对 319 +/- 17 ms) 相似。BMS747158 给药后，对照组和 MI 组兔的任何心血管参数和 ECG 波形均无基线变化。
BMS747158 心脏成像可清晰检测慢性 MI，而不会导致伴有心脏损伤的兔发生任何心血管改变。
