EFFECTS OF OUABAIN ON TECHNETIUM-99M-Q12 AND TL-201 EXTRACTION AND RETENTION BY ISOLATED RAT-HEART

The mechanisms of myocardial extraction and retention of the new catio nic lipophilic radionuclide imaging agent Tc-99m-Q12 are currently unk nown, We hypothesized that Tc-99m-Q12 has satisfactory single-pass ext raction independent of active transport processes and longer cellular retention than Tl-201 for rapid and sustained cardiac imaging to diffe rentiate perfusion defects. Methods: Isolated rat hearts were perfused at constant flow with Krebs-Henseleit buffer enriched with bovine red blood cells (30%-40%), The indicator dilution method was used to meas ure the single-pass maximum extraction (E(max)) and net extraction (E( net)(t)) of Tl-201 and Tc-99m-Q12 over 15 min during control perfusion (n = 11) and during normal (1 mu M, n = 6) and high cardiotoxic (50 m u M, n = 11) dose infusions of the digitalis glycoside, ouabain. Resul ts: The E(max) of Tl-201 was greater than Tc-99m-Q12 E(max) (0.73 +/- 0.01 and 0.29 +/- 0.01, respectively). At 3 min of perfusion, Tl-201 E (net) was greater than Tc-99m-Q12 E(net) (0.40 +/- 0.01 and 0.11 +/- 0 .00, respectively). Between 3 and 15 min, Tl-201 E(net) was decreasing by a rate of 2% per minute while Tc-99m-Q12 E(net) was decreasing by less than 0.1% per minute. Ouabain decreased Tl-201 E(max) but did not change (TC)-T-99m-Q12 E(max). High-dose ouabain decreased Tl-201 E(ne t) at 3 min and Tc-99m-Q12 E(net) at 10 and 15 min, Conclusion: Ouabai n reduced Tl-201 E(max) but not Tc-99m-Q12 E(max). Therefore, the cell ular extraction process for Tc-99m-Q12 is different from that of Tl-20 1. Since the E(net)(t) of Tc-99m-Q12 was reduced in the presence of hi gh doses of ouabain while E(max) was unchanged, Tc-99m-Q12 extraction and retention appear to be controlled by different processes. Extracti on and release kinetics of Tc-99m-Q12 were not changed with a low dose analogous to the human therapeutic levels of ouabain.