Effects of ouabain on technetium-99m-Q12 and thallium-201 extraction and retention by isolated rat heart.
The mechanisms of myocardial extraction and retention of the new cationic lipophilic radionuclide imaging agent 99mTc-Q12 are currently unknown. We hypothesized that 99mTc-Q12 has satisfactory single-pass extraction independent of active transport processes and longer cellular retention than 201Tl for rapid and sustained cardiac imaging to differentiate 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 measure the single-pass maximum extraction (Emax) and net extraction (Enet(t)) of 201Tl and 99mTc-Q12 over 15 min during control perfusion (n = 11) and during normal (1 microM, n = 6) and high cardiotoxic (50 microM, n = 11) dose infusions of the digitalis glycoside, ouabain.


RESULTS
The Emax of 201Tl was greater than 99mTc-Q12 Emax (0.73 +/- 0.01 and 0.29 +/- 0.01, respectively). At 3 min of perfusion, 201Tl Enet was greater than 99mTc-Q12 Enet (0.40 +/- 0.01 and 0.11 +/- 0.00, respectively). Between 3 and 15 min, 201Tl Enet was decreasing by a rate of 2% per minute while 99mTc-Q1 2 Enet was decreasing by less than 0.1 % per minute. Ouabain decreased 201TI Emax but did not change 99mTc-Q12 Emax. High-dose ouabain decreased 201Tl Enet at 3 min and 99-Tc-Q12 Enet at 10 and 15 min.


CONCLUSIONS
Ouabain reduced 201Tl Emax but not 99mTc-Q12 Emax. Therefore, the cellular extraction process for 99mTc-Q12 is different from that of 201Tl. Since the Enet(t) of 99mTc-Q12 was reduced in the presence of high doses of ouabain while Emax was unchanged, 99mTc-Q12 extraction and retention appear to be controlled by different processes. Extraction and release kinetics of 99mTc-Q12 were not changed with a low dose analogous to the human therapeutic levels of ouabain.
McGoron
A J
AJ
Division of Nuclear Medicine, Department of Radiology, University of Cincinnati, OHIO 45267-0577, USA.
Gerson
M C
MC
Biniakiewicz
D S
DS
Washburn
L C
LC
Millard
R W
RW
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002417:Cattle; D004912:Erythrocytes; D005663:Furans / Q000493:pharmacokinetics; D006321:Heart / Q000000981:diagnostic imaging* / Q000187:drug effects; D007201:Indicator Dilution Techniques; D008297:Male; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D010042:Ouabain / Q000494:pharmacology*; D010477:Perfusion; D011877:Radionuclide Imaging; D051381:Rats; D013794:Thallium Radioisotopes / Q000493:pharmacokinetics
D002316:Cardiotonic Agents; D005663:Furans; D015609:Organotechnetium Compounds; D013794:Thallium Radioisotopes; C078496:technetium Tc 99m Q12; D010042:Ouabain