Extraction and retention of technetium-99m Q12, technetium-99m sestamibi, and thallium-201 in isolated rat heart during coronary acidemia.

Technetium-99m Q12 and 99mTc-sestamibi are cationic lipophilic myocardial perfusion imaging tracers. Because myocardium in areas of ischemia becomes acidotic, experiments were designed to differentiate the effects of myocardial perfusate pH on radiotracer extraction and retention independent of substrate availability. We hypothesized that 99mTc-Q12 and 99mTc-sestamibi single-pass uptake and retention would be unaffected by a modest reduction in coronary perfusate pH. Isolated rat hearts were perfused at constant flow with Krebs-Henseleit buffer enriched with bovine red blood cells (20%). The indicator dilution method was used to measure the maximum extraction (Emax) and net extraction (Enet) of thallium-201 and 99mTc-Q12 (n = 8) or 201Tl and 99mTc sestamibi (n = 7) during baseline perfusion (pH = 7.4), during acidemic (pH = 6.7) perfusion, and during a restitution period with normal perfusate (pH = 7.4). 201Tl Emax (0.71+/-0.03) was greater than either 99mTc-Q12 or 99mTc-sestamibi Emax (0.27+/-0.02 and 0.26+/-0.01 respectively, P<0.0001). Acidemia significantly reduced 201Tl Emax (0.65+/-0.03, P<0.02) but not 99mTc-Q12 or 99mTc-sestamibi Emax (0.25+/-0.02 and 0.24+/-0.02 respectively). During control perfusion Enet of 201Tl was greater than that of 99mTc-Q12 at 3 and 5 min and greater than that of 99mTc-sestamibi at 3 min. 99mTc-Q12 Enet was less than 99mTc-sestamibi Enet at 3, 5, and 10 min. Acidemia decreased 201Tl and 99mTc-sestamibi Enet at 3, 5, and 10 min but had no effect on 99mTc-Q12 Enet. It is concluded that Emax of 99mTc-Q12 is less than that of 201Tl but is not different from that of 99mTc-sestamibi. Enet of 99mTc-Q12 is less than that of 99mTc-sestamibi.

Effects of ouabain on technetium-99m-Q12 and thallium-201 extraction and retention by isolated rat heart.

UNLABELLED: 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. CONCLUSION: 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.

Reliable preparation of 99mTc (V) DMSA by a simple modified method using a commercial kit for 99mTc (III) DMSA.

99mTc pentavalent dimercaptosuccinic acid [99mTc (V) DMSA], a useful agent for imaging thyroid medullary carcinoma and other tumors, can be reliably prepared by addition of NaHCO3 and then Na99mTcO4 to a commercial kit for 99mTc trivalent DMSA [99mTc (III) DMSA], followed by bubbling oxygen through the solution for 10 min. 99mTc (V) DMSA made by this method is radiochemically pure and stable for 24 h, and it gives a rat biodistribution similar to that of the agent made by previous methods. Clinical biodistribution and radiation dosimetry studies are planned.