A New 18F-Labeled Myocardial PET Tracer: Myocardial Uptake After Permanent and Transient Coronary Occlusion in Rats
Takahiro Higuchi 1*,
Stephan G. Nekolla 1,
Marc M. Huisman 1,
Sybille Reder 1,
Thorsten Poethko 1,
Ming Yu 2,
Hans-Jurgen Wester 1,
David S. Casebier 2,
Simon P. Robinson 2,
Rene M. Botnar 1,
and
Markus Schwaiger 1
1 Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany
2 Departments of Discovery Chemistry and Discovery Biology, Bristol-Myers Squibb Medical Imaging, North Billerica, Massachusetts
* To whom correspondence should be addressed. E-mail: higuchi{at}po2.nsknet.or.jp.
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Abstract |
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Conventional myocardial perfusion PET tracers require onsite tracer production because of their short radioactive half-lives. To investigate the potential of a new 18F-labeled pyridazinone analog (18F-BMS-747158-02), we characterized this tracer in a rat model of permanent and transient coronary occlusion using small-animal PET. Methods: Myocardial 18F-BMS-747158-02 distribution in healthy rats (n = 7), rats with transient (3-min) left coronary artery occlusion (n = 11), and rats with permanent left coronary occlusion (n = 11) was analyzed with a dedicated small-animal PET scanner. Results: Normal hearts demonstrated intense and almost homogeneous tracer uptake throughout the left ventricle for more than 2 h. During permanent coronary occlusion, PET demonstrated perfusion defects, which remained unchanged (37.6% ± 8.8%, 37.4% ± 10.2%, and 36.2% ± 9.8% left ventricle at 15, 45, and 115 min, respectively, after tracer injection). After transient ischemia, the induced defect size decreased significantly after reperfusion (16.2% ± 9.3%, 6.0% ± 6.5%, and 1.4% ± 1.3% left ventricle). Tracer reinjection after transient ischemia resulted in normalization of the induced defect. Conclusion: Coronary occlusion yielded distinct myocardial 18F-BMS-747158-02 uptake defects in the area of ischemia, which demonstrated normalization of activity after reperfusion and reinjection. These promising kinetic parameters may allow for assessment of flow using exercise–rest protocols similar to those used in combination with exercise and rest perfusion SPECT.
Key Words:
cardiology (clinical), PET, animal imaging, 18F, infarction, ischemia, perfusion
