Evaluation of the novel myocardial perfusion positron-emission tomography tracer 18F-BMS-747158-02: Comparison to 13N-ammonia and validation with microspheres in a pig model

S. G. Nekolla, S. Reder, A. Saraste, T. Higuchi, G. Dzewas, A. Preissel, M. Huisman, T. Poethko, T. Schuster, M. Yu, S. Robinson, D. Casebier, J. Henke, H. J. Wester, M. Schwaiger

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

BACKGROUND-: Positron-emission tomography (PET) tracers for myocardial perfusion are commonly labeled with short-lived isotopes that limit their widespread clinical use. F-BMS-747158-02 (F-BMS) is a novel pyridaben derivative that was evaluated for assessment of myocardial perfusion by comparison with N-ammonia (NH3) and with radioactive microspheres in a pig model. METHODS AND RESULTS-: Fourteen pigs injected with 500 MBq of NH3 or 100 to 200 MBq of F-BMS underwent dynamic PET at rest and during pharmacological stress. In 8 of these pigs, F-BMS was injected during stress combined with transient, 2.5-minute constriction of the left anterior descending coronary artery. Radioactive microspheres were coinjected with F-BMS. Ratios of myocardial tracer uptake to surrounding tissues were determined, and myocardial blood flow was quantified by compartmental modeling. Both tracers showed high and homogeneous myocardial uptake. Compared with NH3, F-BMS showed higher activity ratios between myocardium and blood (rest 2.5 versus 4.1; stress 2.1 versus 5.8), liver (rest 1.2 versus 1.8; stress 0.7 versus 2.0), and lungs (rest 2.5 versus 4.2; stress 2.9 versus 6.4). Regional myocardial blood flow assessed with F-BMS PET showed good correlation (r=0.88, slope=0.84) and agreement (mean difference -0.10 [25th percentile -0.3, 75th percentile 0.1 mL • min • g]) with that measured with radioactive microspheres over a flow range from 0.1 to 3.0 mL • min • g. The extent of defects induced by left anterior descending coronary artery constriction measured by F-BMS and microspheres also correlated closely (r=0.63, slope=1.1). CONCLUSIONS-: F-BMS-747158-02 is a very attractive new PET perfusion tracer that allows quantitative assessment of regional myocardial perfusion over a wide flow range. The long half-life of F renders this tracer useful for clinical PET/CT applications in the workup of patients with suspected or proven coronary artery disease.

Original languageEnglish
Pages (from-to)2333-2342
Number of pages10
JournalCirculation
Volume119
Issue number17
DOIs
Publication statusPublished - May 5 2009
Externally publishedYes

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Microspheres
Ammonia
Positron-Emission Tomography
Swine
Perfusion
Constriction
Coronary Vessels
Regional Blood Flow
Isotopes
Half-Life
Coronary Artery Disease
Myocardium
BMS 747158-02
Pharmacology
Lung
Liver

Keywords

  • Ischemia
  • Microspheres
  • Perfusion
  • Positron-emission tomography
  • Regional blood flow

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Evaluation of the novel myocardial perfusion positron-emission tomography tracer 18F-BMS-747158-02 : Comparison to 13N-ammonia and validation with microspheres in a pig model. / Nekolla, S. G.; Reder, S.; Saraste, A.; Higuchi, T.; Dzewas, G.; Preissel, A.; Huisman, M.; Poethko, T.; Schuster, T.; Yu, M.; Robinson, S.; Casebier, D.; Henke, J.; Wester, H. J.; Schwaiger, M.

In: Circulation, Vol. 119, No. 17, 05.05.2009, p. 2333-2342.

Research output: Contribution to journalArticle

Nekolla, SG, Reder, S, Saraste, A, Higuchi, T, Dzewas, G, Preissel, A, Huisman, M, Poethko, T, Schuster, T, Yu, M, Robinson, S, Casebier, D, Henke, J, Wester, HJ & Schwaiger, M 2009, 'Evaluation of the novel myocardial perfusion positron-emission tomography tracer 18F-BMS-747158-02: Comparison to 13N-ammonia and validation with microspheres in a pig model', Circulation, vol. 119, no. 17, pp. 2333-2342. https://doi.org/10.1161/CIRCULATIONAHA.108.797761
Nekolla, S. G. ; Reder, S. ; Saraste, A. ; Higuchi, T. ; Dzewas, G. ; Preissel, A. ; Huisman, M. ; Poethko, T. ; Schuster, T. ; Yu, M. ; Robinson, S. ; Casebier, D. ; Henke, J. ; Wester, H. J. ; Schwaiger, M. / Evaluation of the novel myocardial perfusion positron-emission tomography tracer 18F-BMS-747158-02 : Comparison to 13N-ammonia and validation with microspheres in a pig model. In: Circulation. 2009 ; Vol. 119, No. 17. pp. 2333-2342.
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abstract = "BACKGROUND-: Positron-emission tomography (PET) tracers for myocardial perfusion are commonly labeled with short-lived isotopes that limit their widespread clinical use. F-BMS-747158-02 (F-BMS) is a novel pyridaben derivative that was evaluated for assessment of myocardial perfusion by comparison with N-ammonia (NH3) and with radioactive microspheres in a pig model. METHODS AND RESULTS-: Fourteen pigs injected with 500 MBq of NH3 or 100 to 200 MBq of F-BMS underwent dynamic PET at rest and during pharmacological stress. In 8 of these pigs, F-BMS was injected during stress combined with transient, 2.5-minute constriction of the left anterior descending coronary artery. Radioactive microspheres were coinjected with F-BMS. Ratios of myocardial tracer uptake to surrounding tissues were determined, and myocardial blood flow was quantified by compartmental modeling. Both tracers showed high and homogeneous myocardial uptake. Compared with NH3, F-BMS showed higher activity ratios between myocardium and blood (rest 2.5 versus 4.1; stress 2.1 versus 5.8), liver (rest 1.2 versus 1.8; stress 0.7 versus 2.0), and lungs (rest 2.5 versus 4.2; stress 2.9 versus 6.4). Regional myocardial blood flow assessed with F-BMS PET showed good correlation (r=0.88, slope=0.84) and agreement (mean difference -0.10 [25th percentile -0.3, 75th percentile 0.1 mL • min • g]) with that measured with radioactive microspheres over a flow range from 0.1 to 3.0 mL • min • g. The extent of defects induced by left anterior descending coronary artery constriction measured by F-BMS and microspheres also correlated closely (r=0.63, slope=1.1). CONCLUSIONS-: F-BMS-747158-02 is a very attractive new PET perfusion tracer that allows quantitative assessment of regional myocardial perfusion over a wide flow range. The long half-life of F renders this tracer useful for clinical PET/CT applications in the workup of patients with suspected or proven coronary artery disease.",
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T1 - Evaluation of the novel myocardial perfusion positron-emission tomography tracer 18F-BMS-747158-02

T2 - Comparison to 13N-ammonia and validation with microspheres in a pig model

AU - Nekolla, S. G.

AU - Reder, S.

AU - Saraste, A.

AU - Higuchi, T.

AU - Dzewas, G.

AU - Preissel, A.

AU - Huisman, M.

AU - Poethko, T.

AU - Schuster, T.

AU - Yu, M.

AU - Robinson, S.

AU - Casebier, D.

AU - Henke, J.

AU - Wester, H. J.

AU - Schwaiger, M.

PY - 2009/5/5

Y1 - 2009/5/5

N2 - BACKGROUND-: Positron-emission tomography (PET) tracers for myocardial perfusion are commonly labeled with short-lived isotopes that limit their widespread clinical use. F-BMS-747158-02 (F-BMS) is a novel pyridaben derivative that was evaluated for assessment of myocardial perfusion by comparison with N-ammonia (NH3) and with radioactive microspheres in a pig model. METHODS AND RESULTS-: Fourteen pigs injected with 500 MBq of NH3 or 100 to 200 MBq of F-BMS underwent dynamic PET at rest and during pharmacological stress. In 8 of these pigs, F-BMS was injected during stress combined with transient, 2.5-minute constriction of the left anterior descending coronary artery. Radioactive microspheres were coinjected with F-BMS. Ratios of myocardial tracer uptake to surrounding tissues were determined, and myocardial blood flow was quantified by compartmental modeling. Both tracers showed high and homogeneous myocardial uptake. Compared with NH3, F-BMS showed higher activity ratios between myocardium and blood (rest 2.5 versus 4.1; stress 2.1 versus 5.8), liver (rest 1.2 versus 1.8; stress 0.7 versus 2.0), and lungs (rest 2.5 versus 4.2; stress 2.9 versus 6.4). Regional myocardial blood flow assessed with F-BMS PET showed good correlation (r=0.88, slope=0.84) and agreement (mean difference -0.10 [25th percentile -0.3, 75th percentile 0.1 mL • min • g]) with that measured with radioactive microspheres over a flow range from 0.1 to 3.0 mL • min • g. The extent of defects induced by left anterior descending coronary artery constriction measured by F-BMS and microspheres also correlated closely (r=0.63, slope=1.1). CONCLUSIONS-: F-BMS-747158-02 is a very attractive new PET perfusion tracer that allows quantitative assessment of regional myocardial perfusion over a wide flow range. The long half-life of F renders this tracer useful for clinical PET/CT applications in the workup of patients with suspected or proven coronary artery disease.

AB - BACKGROUND-: Positron-emission tomography (PET) tracers for myocardial perfusion are commonly labeled with short-lived isotopes that limit their widespread clinical use. F-BMS-747158-02 (F-BMS) is a novel pyridaben derivative that was evaluated for assessment of myocardial perfusion by comparison with N-ammonia (NH3) and with radioactive microspheres in a pig model. METHODS AND RESULTS-: Fourteen pigs injected with 500 MBq of NH3 or 100 to 200 MBq of F-BMS underwent dynamic PET at rest and during pharmacological stress. In 8 of these pigs, F-BMS was injected during stress combined with transient, 2.5-minute constriction of the left anterior descending coronary artery. Radioactive microspheres were coinjected with F-BMS. Ratios of myocardial tracer uptake to surrounding tissues were determined, and myocardial blood flow was quantified by compartmental modeling. Both tracers showed high and homogeneous myocardial uptake. Compared with NH3, F-BMS showed higher activity ratios between myocardium and blood (rest 2.5 versus 4.1; stress 2.1 versus 5.8), liver (rest 1.2 versus 1.8; stress 0.7 versus 2.0), and lungs (rest 2.5 versus 4.2; stress 2.9 versus 6.4). Regional myocardial blood flow assessed with F-BMS PET showed good correlation (r=0.88, slope=0.84) and agreement (mean difference -0.10 [25th percentile -0.3, 75th percentile 0.1 mL • min • g]) with that measured with radioactive microspheres over a flow range from 0.1 to 3.0 mL • min • g. The extent of defects induced by left anterior descending coronary artery constriction measured by F-BMS and microspheres also correlated closely (r=0.63, slope=1.1). CONCLUSIONS-: F-BMS-747158-02 is a very attractive new PET perfusion tracer that allows quantitative assessment of regional myocardial perfusion over a wide flow range. The long half-life of F renders this tracer useful for clinical PET/CT applications in the workup of patients with suspected or proven coronary artery disease.

KW - Ischemia

KW - Microspheres

KW - Perfusion

KW - Positron-emission tomography

KW - Regional blood flow

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