Myocardial imaging with novel Tc-99m labeled aryl bidentate isonitriles

Abstract

1905

Objectives: Sestamibi, hexakis-(t-butylisonitrile) technetium-99m, is a commercial product used in myocardial imaging with SPECT. Our goal was to synthesis, radiolabel and evaluate a novel series of aryl bidentate isonitriles as metal chelating ligands. In this case, metal coordination requires only three aryl isonitrile molecules.

Methods: Several aryl bidentate isonitriles were synthesized for this study including, 1-isocyano-2-(isocyanomethyl)benzene(a), 1,2-bis(isocyanomethyl)benzene(b), and 1,2-di(isocyano)benzene(c). The isonitrile in ethanol was added to stannous gluoheptonate and the solution was filtered. To this solution was added 99mTcO4- in saline and the solution was stirred for 5 min before filtering. The rehenium complexes with the predicted unique structure are under investigation.

Results: The Tc-99m labeled aryl bidentate isonitriles showed pronounced myocardial uptake and retention for over 60 min in rats after injection of 100mCi of the Tc-99m complex. Comparison to Tc-99m sestamibi shows similar heart uptake for all agents. Sestamibi shows higher uptake in gut and the bidantate complexes show higher uptake in the liver. The unique structure of these aryl bidentate isonitrile ligands and the proximity to the aryl moiety to the metal complex entity allows better charge distribution over the molecule and enhanced lipophilicity. Therefore, its potential penetration of cell membranes as a function of flow may improve.

Conclusions: The newly developed aryl bidentate isonitrile Tc-99m complex shows strong potential as a blood flow imaging agent and may show specificity for tumors that are receptive to lipophilic cationic compounds.