Differential effects of cyclodextrins and derivatives on the biological behavior of the myocardial perfusion imaging agent 99mTcN-NOET.

In addition to improving drug solubilization, cyclodextrins (CDs) also affect the biological behavior of the included compound. We evaluated the effects of two natural CDs beta-CD and gamma-CD, and six beta-CD derivatives, Dimeb, Trimeb, SBb, 2-HP, 6AD, and 6 MTU on the biological behavior of (99m)TcN-NOET, a technetium-99m-labeled, lipophilic compound readily detectable through radioactivity assessment. Determination of CDs' affinities for (99m)TcN-NOET indicated that the cavity size of gamma-CD was not suitable for (99m)TcN-NOET inclusion, and that beta-CD derivatization mostly resulted in decreased CDs affinities for (99m)TcN-NOET to various extents compared with the natural beta-CD.

Verapamil does not inhibit 99mTcN-NOET uptake in situ in normal or ischemic canine myocardium.

Unlabelled: Bis(N-ethoxy,N-ethyldithiocarbamato)nitrido technetium (V) ((99m)Tc) ((99m)TcN-NOET) is a new myocardial perfusion imaging agent currently undergoing phase III clinical trials in the United States and in Europe. (99m)TcN-NOET cellular uptake has been shown to be inhibited by the calcium channel inhibitor verapamil in cultured newborn rat cardiomyocytes. However, the effect of verapamil on in situ (99m)TcN-NOET myocardial uptake remains unknown.

Myocardial kinetics of TcN-NOET: a neutral lipophilic complex tracer of regional myocardial blood flow.

Unlabelled: [Bis (N-etoxy, N ethyl dithiocarbamato) nitrido] 99mTc (V) (TcN-NOET) is a new neutral lipophilic myocardial imaging agent proposed for clinical use for detecting coronary artery disease. We studied the relation between myocardial retention of TcN-NOET and myocardial blood flow (MBF) in a canine model.

Methods: A wide range of MBF was induced by partial regional coronary occlusion and dipyridamole infusion (protocols 1,2 and 3).