Blood Clearance of &lt;sup&gt;99m&lt;/sup&gt;Tc-Trimethyl-Br-IDA Discriminates between Different Degrees of Severe Liver Ischaemia &amp;ndash; Reperfusion Injury in the Rat

Chavez-Cartaya, R.; Ramírez, Pablo; Fuente, Teodomiro; DeSola, Gilda Pino; Marín, J. Muñoz; Piñero, Antonio; Parrilla, Pascual; Jamieson, Neville V.

doi:10.1159/000129542

Cited by 10 publications

(11 citation statements)

References 15 publications

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“…It was argued that elevation of serum enzymes indicates that membrane rupture and cell death had already occurred before the study at 1 wk, and it was assumed that if data had been collected at earlier times (2,4,6,24,48,72, or 96 h) after introduction of the diet, it could have been possible to show cell damage before death by demonstrating a normal uptake rate but a prolonged excretory half-life (22). This argument is supported by the previously documented unperturbed 99m Tc-hydroxyiminodiacetic acid uptake observed in chronic liver disease in a few studies (21)(22)(23)36). These studies used thiacetarsamide, CCl4, copper, and ischemia to induce liver damage; however, these changes are not representative of human NASH.…”

Section: Discussionsupporting

confidence: 55%

“…Several studies in patients with acute and chronic parenchymal liver disease (5,20) have shown a correlation between hepatobiliary function assessed by 99m Tc-mebrofenin scintigraphy and the histopathologic severity of the underlying pathology (21)(22)(23). Therefore, HBS would be of great clinical importance for the follow-up of patients during pharmacologic therapy…”

Section: Discussionmentioning

confidence: 99%

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Comparison Between the Values of the Hepatic Uptake Rate Obtained by 2 Methods, Using Hepatobiliary Scintigraphy in Patients with Nonalcoholic Steatohepatitis

Al-Shakhrah

AlSharif²,

Abu-Sneineh³

2010

Journal of Nuclear Medicine Technology

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99m Tc-mebrofenin hepatobiliary scintigraphy has been introduced for the noninvasive assessment of liver function in the clinical setting and in experimental research. Methods: During a period of 2 y, 15 patients with fatty livers diagnosed as having nonalcoholic steatohepatitis underwent hepatobiliary scintigraphy using the radiopharmaceutical agent 99m Tc-labeled mebrofenin. After intravenous administration of 85 MBq of 99m Tc-mebrofenin, a dynamic image was acquired with the liver and heart in the field of view. In this study, a comparison between the values of hepatic uptake rate obtained by applying 2 methods in patients with nonalcoholic steatohepatitis-multiple-time graphical analysis (Gjedde-Patlak plot) and the differentiation between different regions of interest using hepatobiliary scintigraphy-was made. Results: The values of the uptake rate reveal that uptake obtained by applying the second method are significantly higher than that obtained by applying the first one (P 5 0.001). A strong positive association (n 5 15; r 5 0.92; R 2 5 0.84) was found between these measurements. From a Bland-Altman statistical test that was performed on the results we also found that 87% of the cases (13/15) were within 1.96 SD. Conclusion: The Gjedde-Patlak analysis method can be considered as an alternative technique to find and calculate the hepatic uptake rate.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Comparison Between the Values of the Hepatic Uptake Rate Obtained by 2 Methods, Using Hepatobiliary Scintigraphy in Patients with Nonalcoholic Steatohepatitis

Al-Shakhrah

AlSharif²,

Abu-Sneineh³

2010

Journal of Nuclear Medicine Technology

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“…Hepatic extraction fraction and T 1/2 peak , measured by HBS, were used as a noninvasive method of evaluating hepatic function after ischemia-reperfusion injury to quantify the protective effect of new interventions on ischemia-reperfusion injury (81)(82)(83).…”

Section: Hbs In Experimental Surgical Researchmentioning

confidence: 99%

Nuclear Imaging Techniques for the Assessment of Hepatic Function in Liver Surgery and Transplantation

Graaf¹,

Bennink²,

Veteläinen³

et al. 2010

J Nucl Med

138

120

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This review describes the application of 2 nuclear imaging techniques for assessment of hepatic function in the setting of liver surgery and transplantation. The biochemical and technical background, as well as the clinical applications, of 99m Tc-labeled diethylenetriaminepentaacetic acid galactosyl human serum albumin (GSA) scintigraphy and hepatobiliary scintigraphy (HBS) with 99m Tc-labeled iminodiacetic acid derivates is discussed. 99m Tc-mebrofenin is considered the most suitable iminodiacetic acid agent for 99m Tc-HBS. 99m Tc-GSA scintigraphy and 99m Tcmebrofenin HBS are based on 2 different principles. 99m Tc-GSA scintigraphy is a receptor-mediated technique whereas HBS represents hepatic uptake and excretion function. Both techniques are noninvasive and provide visual and quantitative information on both total and regional liver function. They can be used for preoperative assessment of future remnant liver function, follow-up after preoperative portal vein embolization, and evaluation of postoperative liver regeneration. In liver transplantation, these methods are used to assess graft function and biliary complications.

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“…In this regard, mebrofenin -N- (3-bromo-2,4,6-trimethyl-acetanilide)iminodiacetic acid -and related compounds possess exclusive affinity for hepatocytes followed by transport into bile [3][4][5][6][7][8][9][10][11][12][13]. Although relevant hepatobiliary transporters have been well studied [14,15], gaps remain in critical areas and the identity of specific mebrofenin transporter(s) is unknown.…”

Section: Introductionmentioning

confidence: 99%

Systemic and local release of inflammatory cytokines regulates hepatobiliary excretion of 99mTc-mebrofenin

Joseph

Bhargava

Tronco

et al. 2008

Nuclear Medicine Communications

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Objectives-Imaging agents capable of providing cell compartment-specific information will facilitate studies of pathophysiological mechanisms, natural history of diseases, and therapeutic development. To demonstrate the effects of liver injury on the disposal of the organic anion mebrofenin, we performed animal studies.Methods-Acute liver injury was induced in Fischer 344 rats with 0.25-1 ml/kg single doses of carbon tetrachloride followed by studies of animals over 4 weeks. The liver injury was analyzed by blood tests and histological grading. Additional rats were treated with lipopolysaccharide, interleukin-6 or tumor necrosis factor-α to activate inflammatory events. Hepatic clearance of 99m Tc-mebrofenin was studied with dynamic imaging and fractional retention after 60 min of peak hepatic mebrofenin activity was determined.Results-In healthy rats, only 24 ± 2% of peak mebrofenin activity was retained in the liver after 60 min. By contrast, 24 h after carbon tetrachloride, virtually all mebrofenin activity was retained in the liver (P < 0.001). Three weeks were required for mebrofenin excretion to become normal after carbon tetrachloride administration. In this situation, we found that Kupffer cell activity was increased. In addition, the abnormality in mebrofenin excretion was reproduced by lipopolysaccharide, which activates Kupffer cells. Moreover, mebrofenin excretion was highly sensitive to interleukin-6 and/or tumor necrosis factor-α, which help mediate the Kupffer cell response.Conclusion-Hepatobiliary excretion of mebrofenin was affected rapidly and over an extended period by inflammatory cytokines released after liver injury. The remarkable sensitivity of mebrofenin excretion to cytokines suggests that 99m Tc-mebrofenin imaging will be helpful for assessing cytokine-mediated liver inflammation.

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Blood Clearance of <sup>99m</sup>Tc-Trimethyl-Br-IDA Discriminates between Different Degrees of Severe Liver Ischaemia – Reperfusion Injury in the Rat

Cited by 10 publications

References 15 publications

Comparison Between the Values of the Hepatic Uptake Rate Obtained by 2 Methods, Using Hepatobiliary Scintigraphy in Patients with Nonalcoholic Steatohepatitis

Comparison Between the Values of the Hepatic Uptake Rate Obtained by 2 Methods, Using Hepatobiliary Scintigraphy in Patients with Nonalcoholic Steatohepatitis

Nuclear Imaging Techniques for the Assessment of Hepatic Function in Liver Surgery and Transplantation

Systemic and local release of inflammatory cytokines regulates hepatobiliary excretion of 99mTc-mebrofenin

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