Monocationic radiotracer kinetics and myocardial infarct size

A perfused rat heart study

David R. Okada, Zhonglin Liu, Delia Beju, Robert D. Okada, Gerald Johnson

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objective: To compare the myocardial kinetics of three 99mtechnetium-labeled monocationic tracers [methoxy- isobutylisonitrile (MIBI), tetrofosmin, and Q12] in a model of ischemia-reperfusion (IR) to determine their abilities to assess myocardial viability. Methods: Isolated perfused rat hearts (n = 30) were studied in control and IR groups for each tracer. IR hearts were treated with 120 min global no-flow followed by 5 min reflow, then 60 min tracer uptake/clearance. Tracer kinetics were monitored using a scintillation detector. Results: This model produced significant myocardial injury, without significant differences in the percentage of injured myocardium by triphenyltetrazolium chloride (TTC) staining and creatine kinase (CK) assay. Transmission electron microscopy analysis also confirmed necrosis with abundant mitochondrial damage in the IR hearts. All three IR groups exhibited significantly less mean (±standard error of the mean) tracer retention than matched controls (MIBI 73.4 ± 4.9% vs. 96.9 ± 1.76%, tetrofosmin 38.7 ± 4.6% vs. 82.2 ± 3.5%, and Q12 23.0 ± 2.5% vs. 43.8 ± 1.8%, respectively; P < 0.05). Tetrofosmin IR hearts exhibited 54 ± 9% of control myocardial retention, which was significantly less than either MIBI (86 ± 5%, P < 0.05) or Q12 (63 ± 6%, P < 0.05); thus, tetrofosmin provided the best differentiation between nonviable and normal myocardium. Furthermore, tetrofosmin end activity (%id/g) in controls was significantly higher than Q12 (4.09 ± 0.04 vs. 1.71 ± 0.06, respectively, P < 0.05), and tetrofosmin end activity (%id/g) in IR hearts was significantly higher than Q12 (2.19 ± 0.37 vs. 1.06 ± 0.12, respectively, P < 0.05). The correlation between end activity and viable myocardium determined by TTC staining was r = 0.66 (P < 0.05) for MIBI, r = 0.94 (P < 0.05) for tetrofosmin, and r = 0.91 (P < 0.05) for Q12. The correlation between myocardial end activity and myocardial CK leak was r = -0.62 (P < 0.05) for MIBI, r = -0.87 (P < 0.05) for tetrofosmin, and r = -0.89 (P < 0.05) for Q12. Conclusions: Nonviable myocardium can be distinguished from normal myocardium by the retention kinetics of all three monocationic tracers studied. Tetrofosmin and Q12 end activities demonstrate the best correlation with infarct size. However, tetrofosmin kinetics may combine the greatest differentiation between nonviable and normal myocardium, while still retaining adequate activity for imaging.

Original languageEnglish (US)
Pages (from-to)617-627
Number of pages11
JournalAnnals of Nuclear Medicine
Volume22
Issue number7
DOIs
StatePublished - Aug 2008

Fingerprint

Reperfusion
Ischemia
Myocardial Infarction
Myocardium
Staining and Labeling
MB Form Creatine Kinase
Creatine Kinase
Transmission Electron Microscopy
Necrosis
Wounds and Injuries

Keywords

  • Technetium
  • Ischemia
  • Myocardial viability
  • Perfusion imaging agents
  • Reperfusion

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Monocationic radiotracer kinetics and myocardial infarct size : A perfused rat heart study. / Okada, David R.; Liu, Zhonglin; Beju, Delia; Okada, Robert D.; Johnson, Gerald.

In: Annals of Nuclear Medicine, Vol. 22, No. 7, 08.2008, p. 617-627.

Research output: Contribution to journalArticle

Okada, David R. ; Liu, Zhonglin ; Beju, Delia ; Okada, Robert D. ; Johnson, Gerald. / Monocationic radiotracer kinetics and myocardial infarct size : A perfused rat heart study. In: Annals of Nuclear Medicine. 2008 ; Vol. 22, No. 7. pp. 617-627.
@article{4a03c57c4ba546779125d4b9067f6805,
title = "Monocationic radiotracer kinetics and myocardial infarct size: A perfused rat heart study",
abstract = "Objective: To compare the myocardial kinetics of three 99mtechnetium-labeled monocationic tracers [methoxy- isobutylisonitrile (MIBI), tetrofosmin, and Q12] in a model of ischemia-reperfusion (IR) to determine their abilities to assess myocardial viability. Methods: Isolated perfused rat hearts (n = 30) were studied in control and IR groups for each tracer. IR hearts were treated with 120 min global no-flow followed by 5 min reflow, then 60 min tracer uptake/clearance. Tracer kinetics were monitored using a scintillation detector. Results: This model produced significant myocardial injury, without significant differences in the percentage of injured myocardium by triphenyltetrazolium chloride (TTC) staining and creatine kinase (CK) assay. Transmission electron microscopy analysis also confirmed necrosis with abundant mitochondrial damage in the IR hearts. All three IR groups exhibited significantly less mean (±standard error of the mean) tracer retention than matched controls (MIBI 73.4 ± 4.9{\%} vs. 96.9 ± 1.76{\%}, tetrofosmin 38.7 ± 4.6{\%} vs. 82.2 ± 3.5{\%}, and Q12 23.0 ± 2.5{\%} vs. 43.8 ± 1.8{\%}, respectively; P < 0.05). Tetrofosmin IR hearts exhibited 54 ± 9{\%} of control myocardial retention, which was significantly less than either MIBI (86 ± 5{\%}, P < 0.05) or Q12 (63 ± 6{\%}, P < 0.05); thus, tetrofosmin provided the best differentiation between nonviable and normal myocardium. Furthermore, tetrofosmin end activity ({\%}id/g) in controls was significantly higher than Q12 (4.09 ± 0.04 vs. 1.71 ± 0.06, respectively, P < 0.05), and tetrofosmin end activity ({\%}id/g) in IR hearts was significantly higher than Q12 (2.19 ± 0.37 vs. 1.06 ± 0.12, respectively, P < 0.05). The correlation between end activity and viable myocardium determined by TTC staining was r = 0.66 (P < 0.05) for MIBI, r = 0.94 (P < 0.05) for tetrofosmin, and r = 0.91 (P < 0.05) for Q12. The correlation between myocardial end activity and myocardial CK leak was r = -0.62 (P < 0.05) for MIBI, r = -0.87 (P < 0.05) for tetrofosmin, and r = -0.89 (P < 0.05) for Q12. Conclusions: Nonviable myocardium can be distinguished from normal myocardium by the retention kinetics of all three monocationic tracers studied. Tetrofosmin and Q12 end activities demonstrate the best correlation with infarct size. However, tetrofosmin kinetics may combine the greatest differentiation between nonviable and normal myocardium, while still retaining adequate activity for imaging.",
keywords = "Technetium, Ischemia, Myocardial viability, Perfusion imaging agents, Reperfusion",
author = "Okada, {David R.} and Zhonglin Liu and Delia Beju and Okada, {Robert D.} and Gerald Johnson",
year = "2008",
month = "8",
doi = "10.1007/s12149-008-0155-y",
language = "English (US)",
volume = "22",
pages = "617--627",
journal = "Annals of Nuclear Medicine",
issn = "0914-7187",
publisher = "Springer Japan",
number = "7",

}

TY - JOUR

T1 - Monocationic radiotracer kinetics and myocardial infarct size

T2 - A perfused rat heart study

AU - Okada, David R.

AU - Liu, Zhonglin

AU - Beju, Delia

AU - Okada, Robert D.

AU - Johnson, Gerald

PY - 2008/8

Y1 - 2008/8

N2 - Objective: To compare the myocardial kinetics of three 99mtechnetium-labeled monocationic tracers [methoxy- isobutylisonitrile (MIBI), tetrofosmin, and Q12] in a model of ischemia-reperfusion (IR) to determine their abilities to assess myocardial viability. Methods: Isolated perfused rat hearts (n = 30) were studied in control and IR groups for each tracer. IR hearts were treated with 120 min global no-flow followed by 5 min reflow, then 60 min tracer uptake/clearance. Tracer kinetics were monitored using a scintillation detector. Results: This model produced significant myocardial injury, without significant differences in the percentage of injured myocardium by triphenyltetrazolium chloride (TTC) staining and creatine kinase (CK) assay. Transmission electron microscopy analysis also confirmed necrosis with abundant mitochondrial damage in the IR hearts. All three IR groups exhibited significantly less mean (±standard error of the mean) tracer retention than matched controls (MIBI 73.4 ± 4.9% vs. 96.9 ± 1.76%, tetrofosmin 38.7 ± 4.6% vs. 82.2 ± 3.5%, and Q12 23.0 ± 2.5% vs. 43.8 ± 1.8%, respectively; P < 0.05). Tetrofosmin IR hearts exhibited 54 ± 9% of control myocardial retention, which was significantly less than either MIBI (86 ± 5%, P < 0.05) or Q12 (63 ± 6%, P < 0.05); thus, tetrofosmin provided the best differentiation between nonviable and normal myocardium. Furthermore, tetrofosmin end activity (%id/g) in controls was significantly higher than Q12 (4.09 ± 0.04 vs. 1.71 ± 0.06, respectively, P < 0.05), and tetrofosmin end activity (%id/g) in IR hearts was significantly higher than Q12 (2.19 ± 0.37 vs. 1.06 ± 0.12, respectively, P < 0.05). The correlation between end activity and viable myocardium determined by TTC staining was r = 0.66 (P < 0.05) for MIBI, r = 0.94 (P < 0.05) for tetrofosmin, and r = 0.91 (P < 0.05) for Q12. The correlation between myocardial end activity and myocardial CK leak was r = -0.62 (P < 0.05) for MIBI, r = -0.87 (P < 0.05) for tetrofosmin, and r = -0.89 (P < 0.05) for Q12. Conclusions: Nonviable myocardium can be distinguished from normal myocardium by the retention kinetics of all three monocationic tracers studied. Tetrofosmin and Q12 end activities demonstrate the best correlation with infarct size. However, tetrofosmin kinetics may combine the greatest differentiation between nonviable and normal myocardium, while still retaining adequate activity for imaging.

AB - Objective: To compare the myocardial kinetics of three 99mtechnetium-labeled monocationic tracers [methoxy- isobutylisonitrile (MIBI), tetrofosmin, and Q12] in a model of ischemia-reperfusion (IR) to determine their abilities to assess myocardial viability. Methods: Isolated perfused rat hearts (n = 30) were studied in control and IR groups for each tracer. IR hearts were treated with 120 min global no-flow followed by 5 min reflow, then 60 min tracer uptake/clearance. Tracer kinetics were monitored using a scintillation detector. Results: This model produced significant myocardial injury, without significant differences in the percentage of injured myocardium by triphenyltetrazolium chloride (TTC) staining and creatine kinase (CK) assay. Transmission electron microscopy analysis also confirmed necrosis with abundant mitochondrial damage in the IR hearts. All three IR groups exhibited significantly less mean (±standard error of the mean) tracer retention than matched controls (MIBI 73.4 ± 4.9% vs. 96.9 ± 1.76%, tetrofosmin 38.7 ± 4.6% vs. 82.2 ± 3.5%, and Q12 23.0 ± 2.5% vs. 43.8 ± 1.8%, respectively; P < 0.05). Tetrofosmin IR hearts exhibited 54 ± 9% of control myocardial retention, which was significantly less than either MIBI (86 ± 5%, P < 0.05) or Q12 (63 ± 6%, P < 0.05); thus, tetrofosmin provided the best differentiation between nonviable and normal myocardium. Furthermore, tetrofosmin end activity (%id/g) in controls was significantly higher than Q12 (4.09 ± 0.04 vs. 1.71 ± 0.06, respectively, P < 0.05), and tetrofosmin end activity (%id/g) in IR hearts was significantly higher than Q12 (2.19 ± 0.37 vs. 1.06 ± 0.12, respectively, P < 0.05). The correlation between end activity and viable myocardium determined by TTC staining was r = 0.66 (P < 0.05) for MIBI, r = 0.94 (P < 0.05) for tetrofosmin, and r = 0.91 (P < 0.05) for Q12. The correlation between myocardial end activity and myocardial CK leak was r = -0.62 (P < 0.05) for MIBI, r = -0.87 (P < 0.05) for tetrofosmin, and r = -0.89 (P < 0.05) for Q12. Conclusions: Nonviable myocardium can be distinguished from normal myocardium by the retention kinetics of all three monocationic tracers studied. Tetrofosmin and Q12 end activities demonstrate the best correlation with infarct size. However, tetrofosmin kinetics may combine the greatest differentiation between nonviable and normal myocardium, while still retaining adequate activity for imaging.

KW - Technetium

KW - Ischemia

KW - Myocardial viability

KW - Perfusion imaging agents

KW - Reperfusion

UR - http://www.scopus.com/inward/record.url?scp=50949126781&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=50949126781&partnerID=8YFLogxK

U2 - 10.1007/s12149-008-0155-y

DO - 10.1007/s12149-008-0155-y

M3 - Article

VL - 22

SP - 617

EP - 627

JO - Annals of Nuclear Medicine

JF - Annals of Nuclear Medicine

SN - 0914-7187

IS - 7

ER -