Evaluation of potential heart affine compounds by use of the isolated perfused rat heart

Abstract

^99mTc-organocation complexes were screened for heart affinity using the isolated perfused rat heart. The ^99mTc-I compounds are better extracted by the heart and retained in it than the ^99mTc-III compounds. ^99mTcCl₂(DMPE) ₂ ⁺ shows low uptake (15%) and fast washout, but no impairment of uptake after incubation with human serum albumin(HSA), with a modified preparation, initial uptake is not much better (18%) but washout is clearly diminished. ^99mTc(DMPE) ₃ ⁺ is taken up to a greater extent (33%) if administered solely, but when given in conjunction with HSA, uptake decreases to about 4% because of strong affinity of the complex to the protein, but this compound persists well in the tissue. Detergents like tween 80 and dioctylsulphosuccinate are able to cause higher uptake of ^99mTc(DMPE) ₃ ⁺ even in the presence of HSA, thus indicating a diminished binding of the compound to the protein. ^99mTc(CN-t-butyl) ₆ ⁺ shows very high uptake (80%) by the heart, which is only moderately diminished by addition of HSA (t0 38%), and persists excellently in the myocardium. Basic features of the compounds such as accumulation in and elimination from the myocardium as well as plasma protein binding and their mutual relationships are well reflected by the isolated heart model.