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 β-CD and γ-CD, and six β-CD derivatives, Dimeb, Trimeb, SBb, 2-HP, 6AD, and 6 MTU on the biological behavior of 99mTcN-NOET, a technetium-99m-labeled, lipophilic compound readily detectable through radioactivity assessment. Determination of CDs' affinities for 99mTcN-NOET indicated that the cavity size of γ-CD was not suitable for 99mTcN-NOET inclusion, and that β-CD derivatization mostly resulted in decreased CDs affinities for 99mTcN-NOET to various extents compared with the natural β-CD. In vitro and ex vivo experiments performed on newborn rat cardiomyocytes and isolated perfused rat hearts, respectively, showed 1.7- and 2.3-fold maximal differences in 99mTcN-NOET cellular and tissue activities. Regression analyzes indicated no significant correlation between these observed biological differences and the affinities of the eight CDs tested for 99mTcN-NOET or for cellular membranes. In conclusion, CD derivatization often resulted in impaired affinity of the derivatives for the lipophilic compound 99mTcN-NOET. Moreover, the in vitro and ex vivo biological behavior of 99mTcN-NOET was greatly affected depending on the CD used for inclusion of the tracer.