Initial Characterization of an ¹⁸F-Labeled Myocardial Perfusion Tracer

Abstract

PET allows for quantitative, regional myocardial perfusion imaging. The short half-lives of the perfusion tracers currently in use limit their clinical applicability. Here, the biodistribution and imaging quality of a new 18 F-labeled myocardial perfusion agent ( 18 F-BMS-747158-02) in an animal model are described. Methods: The biodistribution of 18 F-BMS-747158-02 was determined at 10 and 60 min after injection. The first-pass extraction fraction of the tracer was measured in isolated rat hearts perfused with the Langendorff method. Small-animal PET imaging was used to study tracer retention. Results: The biodistribution at 10 min after injection demonstrated high myocardial uptake (3.1 percentage injected dose per gram [%ID/g]) accompanied by little activity in the lungs (0.3 %ID/g) and liver (1.0 %ID/g). The tracer showed a high and flow-independent myocardial first-pass extraction fraction, averaging 0.94 (SD 5 0.04). PET imaging provided excellent delineation of myocardial structures. The heartto-lung activity ratio increased from 4.7 to 10.2 between 1 and 15 min after tracer injection (at rest). Adenosine infusion (140 mg/ kg/min) led to a significant increase in myocardial tracer retention (from 1.68 [SD 5 0.23]) s 21 to 3.21 [SD 5 0.92] s 21 ; P 5 0.03). Conclusion: The observation of a high and flow-independent first-pass extraction fraction promises linearity between tracer uptake and myocardial blood flow. Sustained myocardial tracer uptake, combined with high image contrast, will allow for imaging protocols with tracer injection at peak exercise followed by delayed imaging. Thus, 18 F-BMS-747158-02 is a promising new tracer for the quantitative imaging of myocardial perfusion and can be distributed to imaging laboratories without a cyclotron.

Novel PET Probes18F-BCPP-EF and18F-BCPP-BF for Mitochondrial Complex I: A PET Study in Comparison with18F-BMS-747158-02 in Rat Brain

“…However, this technique measures only the first part of glucose metabolism in the phosphorylation of glucose to glucose-6-phosphate by hexokinase (EC 2.7.1.1). Therefore, 18 F-FDG is taken up into not only normal tissues but also inflammatory regions observed in the subacute phase after transient focal ischemia in rodent models (11,12). Because recent reports indicated that several neurodegenerative disorders-schizophrenia, major depression, dementia (13,14), and autism (15)-induced neuroinflammation, 18 F-FDG may lead to underestimation of the neurodegenerative damage in these diseases.…”

“…In contrast, activated inflammatory cells (macrophages and microglia) (4-7) and cancer cells (3,8,9) produce lactate from glucose via lactate dehydrogenase subunit A (EC 1.1.1.27), which is known as the Warburg effect or aerobic glycolysis, showing less than 5% glucose utilization in oxidative phosphorylation and a low contribution of the electron transport system for adenosine triphosphate (ATP) production. 18 F-FDG PET is a well-established technique for the quantitative measurement of the regional metabolic rate of glucose in the brain (10). However, this technique measures only the first part of glucose metabolism in the phosphorylation of glucose to glucose-6-phosphate by hexokinase (EC 2.7.1.1).…”

“…For the quantitative neuroimaging of normal tissues without interference by neuroinflammation, we proposed to apply a specific PET probe for MC-I, 18 F-BMS-747158-02 ( 18 F-BMS) (16), which was originally developed as a myocardial perfusion imaging agent (17,18). Because whole-body PET imaging indicated high uptake and long retention not only in heart but also in the brain (17), we hypothesized that 18 F-BMS might be applicable for detecting neuronal damage in the living brain using PET.…”

Quantification of myocardial blood flow will reform the detection of CAD

“…This has been known for long with 15 O-water which does not produce qualitative perfusion images at all but only quantitative results. The same phenomenon is likely to happen automatically with the new tracers with high extraction fraction 12,13 and also with other tracers after quantification. This means that the traditional criteria for ischemic regions in the images need to be redefined when quantification is applied.…”

“…16 There are, however, some obvious differences between these two tracers. 13 N-ammonia is extracted from blood with an extraction fraction lower than 100% and the extraction is inversely related to the perfusion (Figure 1). When 15 O-water is used, perfusion is estimated from the tracer's washout from the myocardium, whereas with 13 N-ammonia, perfusion is calculated from the tracer's uptake by myocardium.…”