Overall, it is clear that the two new technetium-labeled compounds can provide diagnostic myocardial perfusion imaging both at stress (exercise and pharmacologic) and rest, but they have very different mechanisms of transport in comparison to each other and to thallium. Therefore, new imaging protocols will need to be developed and refined by practical experience as the use of these agents expands. Further investigative work needs to be done to optimize protocols and computer processing of images. In addition, special clinical situations will become associated with the use of these new compounds. Nuclear cardiology will continue to advance during this time of great changes and challenges if informational exchange on these topics continues to flourish and critical clinical trials are completed.

Effects of hypoxia and ouabain on transcapillary exchange of [99mTc]hexakis (2-methoxyisobutylisonitrile) [SESTAMIBI, also known as MIBI or HEXAMIBI] and 201TI were investigated with indicator-dilution studies using isolated rabbit hearts. Peak myocardial extraction (Emax), permeability-surface area products (PScap), and net myocardial extraction (Enet) were compared among serial injections during constant coronary flows. Overall, measures of transcapillary transport (Emax and PScap) for SESTAMIBI were significantly lower (p less than 0.001) than those simultaneously determined for thallium, but estimates of tissue retention (Enet) for SESTAMIBI and thallium were not statistically distinguishable. Hypoxia had no significant effect on mean (+/- s.d.) Emax for SESTAMIBI (0.31 +/- 0.13) or thallium (0.59 +/- 0.11), nor on mean PScap or Enet values. Ouabain (1.5 X 10(-7) M and 1.5 X 10(-6) M) had no effect on SESTAMIBI or thallium Emax (respectively, 0.29 +/- 0.08 and 0.60 +/- 0.05) or on PScap for SESTAMIBI. Thallium PScap was depressed with higher ouabain dose (control, 1.22 +/- 0.40; high ouabain, 1.06 +/- 0.41 ml/min/g; p less than 0.01). Ouabain also caused a significant and progressive increase in average SESTAMIBI Enet (control, 0.23 +/- 0.10 to high ouabain, 0.33 +/- 0.12; p less than 0.05), but depressed thallium Enet (control, 0.38 +/- 0.14 to high ouabain, 0.32 +/- 0.18; p less than 0.01). These results suggest myocardial metabolic and/or functional status have minor influence on transcapillary transport of SESTAMIBI and thallium, but significantly affects cellular retention.

To investigate whether Q12 uptake is affected by myocardial viability, as has been noted for 201Tl and sestamibi, we analyzed the initial and delayed distribution patterns of Q12 in a rat coronary artery occlusion-reperfusion model. METHODS: Animals were intubated and ventilated, and their arterial pressures were monitored. A left thoracotomy was performed. After a 1-hr occlusion and a 1-hr reperfusion of a major branch of the circumflex artery, 201Tl and Q12 were injected intravenously. Radiolabeled microspheres were used to document the areas of risk and reperfusion. The animals were killed at 5 min or 1 hr after administration of the diffusible tracers. Tracer distribution was determined by segmental tissue analysis, and tissue viability was determined by histochemical staining. RESULTS: Both the initial uptake and delayed retention of Q12 are sensitive to myocardial viability as shown by significantly lower uptake (28% +/- 8%) and retention (41% +/- 13%) of Q12 in the nonviable as compared to the viable segments (p < 0.001). In addition, the myocardial retention of Q12 was significantly less in the nonviable tissue when compared to the initial uptake (p < 0.01). CONCLUSION: The clinical implication of these observations suggests that initial and delayed imaging after Q12 administration would reflect both the initial regional blood flow pattern and myocardial viability. Also, delayed imaging of Q12 may reflect viability better than the initial imaging.

Dipyridamole-thallium imaging is a relatively safe and accurate method to evaluate myocardial perfusion and "stress." It is independent of patient motivation, exercise capacity and antianginal medications. Overall it detects coronary artery disease as well as exercise thallium and has already shown utility in prognostic determinations. The continued use of this test on a wide scale appears warranted and additional large scale experience needs to be critically evaluated.

Technetium-99m-[2-(1-methoxybutyl) isonitrile] (MBI) is a potential new compound for the scintigraphic imaging of coronary flow. Evaluation in the blood-perfused isolated rabbit heart model showed this compound to have a myocardial uptake comparable to 201Tl and higher than sestamibi. Although the mean +/- s.d. maximum extraction (Emax) and capillary permeability-surface area product (PScap) of 99mTc-MBI (Emax = 0.45 +/- 0.10, PScap = 1.07 +/- 0.47 ml/min.g) were much less than 201Tl (Emax = 0.71 +/- 0.07, PScap = 2.21 +/- 0.76 ml/min.g, p < 0.0001), the net extraction of 99mTc-MBI (Enet = 0.52 +/- 0.10) was only slightly less than the value for 201Tl (Enet = 0.56 +/- 0.10, p < 0.05). There was no significant difference in the myocardial uptake versus flow between 99mTc-MBI and 201Tl. These data indicate that assessment of relative coronary flow based on the myocardial uptake of 99mTc-MBI should give results comparable to 201Tl. Therefore, 99Tc-MBI may have clinical potential as a radiolabeled myocardial perfusion agent.