Mitochondrial localization and characterization of 99Tc-SESTAMIBI in heart cells by electron probe X-ray microanalysis and 99Tc-NMR spectroscopy

Piwnica‐Worms, David; Kronauge, James F.; LeFurgey, Ann; Backus, Mark; Hockett, Daniel; Ingram, Peter; Lieberman, Melvyn; Holman, B. Leonard; Jones, Alun G.; Davison, Alan

doi:10.1016/0730-725x(94)92459-7

Cited by 53 publications

(32 citation statements)

References 29 publications

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“…However, 18 FDG is a relatively non-specific tracer with many practical limitations, the worst being that in ischemic/reperfused myocardium, it severely underestimates glucose uptake [17][18][19][20][21] which can potentially lead to underestimation of viability. Furthermore, few, if any, radiotracers of "perfusion" represent perfusion alone; most, like 99m Tc sestamibi, 201 Tl, and 13 NH 3 are trapped by energy-dependent processes [22][23][24], which makes them vulnerable to under-estimating the true level of perfusion in energy depleted tissue. There is, therefore, room for improvement.…”

Section: Potential Applications Of Cardiac Hypoxia Imagingmentioning

confidence: 99%

PET imaging of cardiac hypoxia: Opportunities and challenges

Handley¹,

Medina²,

Nagel

et al. 2011

Journal of Molecular and Cellular Cardiology

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Myocardial hypoxia is a major factor in the pathology of cardiac ischemia and myocardial infarction. Hypoxia also occurs in microvascular disease and cardiac hypertrophy, and is thought to be a prime determinant of the progression to heart failure, as well as the driving force for compensatory angiogenesis. The non-invasive delineation and quantification of hypoxia in cardiac tissue therefore has the potential to be an invaluable experimental, diagnostic and prognostic biomarker for applications in cardiology. However, at this time there are no validated methodologies sufficiently sensitive or reliable for clinical use. PET imaging provides real-time spatial information on the biodistribution of injected radiolabeled tracer molecules. Its inherent high sensitivity allows quantitative imaging of these tracers, even when injected at subpharmacological (≥pM) concentrations, allowing the non-invasive investigation of biological systems without perturbing them. PET is therefore an attractive approach for the delineation and quantification of cardiac hypoxia and ischemia. In this review we discuss the key concepts which must be considered when imaging hypoxia in the heart. We summarize the PET tracers which are currently available, and we look forward to the next generation of hypoxia-specific PET imaging agents currently being developed. We describe their potential advantages and shortcomings compared to existing imaging approaches, and what is needed in terms of validation and characterization before these agents can be exploited clinically.

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Section: Potential Applications Of Cardiac Hypoxia Imagingmentioning

confidence: 99%

PET imaging of cardiac hypoxia: Opportunities and challenges

Handley¹,

Medina²,

Nagel

et al. 2011

Journal of Molecular and Cellular Cardiology

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“…MIBI reversibly passes into the cytoplasm via thermodynamic driving forces and irreversibly passes into the mitochondria using the electrical gradient generated by a high negative inner transmembrane mitochondrial potential (28)(29)(30). Accordingly, more intense MIBI concentrations have been found in malignant tumor cells than in normal cells because of the higher electrical gradient of the former (28).…”

mentioning

confidence: 99%

“…The mechanism of cellular radiopharmaceutical accumulation has been reported to depend on the size of a tumor, the blood flow within it (28), and the richness of mitochondria in the tumor cells (28,29). MIBI reversibly passes into the cytoplasm via thermodynamic driving forces and irreversibly passes into the mitochondria using the electrical gradient generated by a high negative inner transmembrane mitochondrial potential (28)(29)(30).…”

mentioning

confidence: 99%

^99mTc-MIBI Imaging in the Presurgical Characterization of Thyroid Follicular Neoplasms: Relationship to Multidrug Resistance Protein Expression

Saggiorato¹,

Angusti²,

Rosas³

et al. 2009

J Nucl Med

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Recently, thyroid 99m Tc-methoxyisobutylisonitrile ( 99m Tc-MIBI) scintiscanning has been proposed in an attempt to preoperatively identify thyroid malignancies, but discrepant results have been reported for oncocytic lesions. The aim of this study was to investigate the usefulness of visual and semiquantitative analyses of 99m Tc-MIBI scintigraphy for preoperatively characterizing thyroid nodules with indeterminate cytologic diagnoses, segregating in advance nononcocytic variants from those that are oncocytic. This study also aimed to analyze the relationship between 99m Tc-MIBI images and P-glycoprotein (P-gp)/multidrug resistance-associated protein-1 (MRP1) immunohistochemical expression. Methods: Fifty-one consecutive patients with cold thyroid nodules cytologically diagnosed as nononcocytic or oncocytic follicular neoplasm were prospectively studied. Visual and semiquantitative 99m Tc-MIBI scanning was performed and the diagnoses of the lesions were histologically proven by subsequent thyroidectomy. Immunohistochemical evaluation of P-gp and MRP1 was also performed on surgical samples. Results: Visual and semiquantitative 99m Tc-MIBI scintiscans showed a low specificity in preoperatively discriminating malignant oncocytic lesions. In nononcocytic nodules, the semiquantitative method was more accurate than the visual (94.44% and 77.78%, respectively). P-gp protein expression was negative in all thyroid lesions, whereas apical plasma membrane MRP1 expression was found in 78% of the lesions with a negative 99m Tc-MIBI retention index, compared with 11% of lesions with a positive retention index, correlating most strongly with a negative 99m Tc-MIBI RI in those cases with strong MRP1 apical expression. Conclusion: Semiquantitative 99m Tc-MIBI scintigraphy is an adjunctive method to predict preoperatively the malignant behavior of nononcocytic follicular thyroid nodules indeterminate at fine-needle aspiration biopsy, with a potential impact on the definition of their clinical management. Moreover, the good correlation found between immunohistochemical apical expression of MRP1 and the scintigraphic findings supports the 99m Tc-MIBI results and provides tissue information on the molecular mechanisms responsible for 99m Tc-MIBI images in thyroid lesions.

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“…The mechanism of Tc-99m MIBI accumulation in tumor has been reported to depend on the size of a tumor, the blood flow and the richness of mitochondria in the tumor cells (Moretti et al, 2005;Piwnica-Worms et al, 1994;Saggiorato et al, 2009). MIBI irreversibly passes into the mitochondria using the electrical gradient generated by a high negative inner transmembrane mitochondrial potential of malignant cells (Chernoff et al, 1993;Moretti et al, 2005;Piwnica-Worms et al, 1994). Also, there is a report that TSH simulates both F-18 FDG PET and Tc-99m MIBI uptake in poorly differentiated papillary thyroid cancer in vitro experiment (Kim et al, 2009).…”

Section: Tc-99m Methoxyisobutylisonitrile (Tc-99m Mibi)mentioning

confidence: 99%