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

Abstract

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.

The emerging role of transport systems in liver function tests

“…The structurally closely related Gd-BOPTA is taken up into rat hepatocytes by Oatp1a1, Oatp1a4, and Oatp1b2 and excreted into bile by Mrp2 (Planchamp et al, 2007). Recently, the scintigraphic agent 99m Tcmebrofenin was introduced for assessing liver function noninvasively (de Graaf et al, 2010a) and for predicting the function of the future remnant liver after liver resection (de Graaf et al, 2010b). Subsequent studies identified OATP1B1 and OATP1B3 as 99m Tc-mebrofenin uptake transporters (de Graaf et al, 2011;Ghibellini et al, 2008).…”

“…In the case of planned liver resections, information on the liver function of individual segments is needed to successfully improve the outcome of this procedure (de Graaf et al, 2010a;Hoekstra et al). Noninvasive methods such as scintigraphy or MRI are already under clinical investigation and have demonstrated to predict the remaining functional liver mass in patients scheduled for resection (de Graaf et al, 2010c).…”

“…Hence, transport proteins are key molecular components of the hepatocellular detoxification system (phase 0 and phase III) and consequently of liver function tests. Liver function tests utilizing exogenous indicators such as indocyanine green (ICG), bromosulphophthalein (BSP), fluorescent bile salt derivatives, agents for magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), or breath tests have been developed to complement the use of endogenous indicators (de Graaf et al, 2010a;Milkiewicz et al, 2000;Millet et al, 2011;Sakka, 2007). Preoperative dynamic liver function tests are part of the routine assessment of patients scheduled for liver resection in many centers (Breitenstein et al, 2009).…”

Transporters involved in the hepatic uptake of 99mTc-mebrofenin and indocyanine green

“…The indocyanine green (ICG) clearance test and technetium-99m ( 99m Tc)-mebrofenin hepatobiliary scintigraphy (HBS) are valuable quantitative dynamic liver function tests used for the assessment of liver function before and after liver surgery (1)(2)(3). 99m Tc-mebrofenin is a 99m Tc-labeled iminodiacetic (IDA) derivate originally used for the diagnosis of a multitude of biliary diseases (4) and since recently for the assessment of liver function (1). ICG is a tricarbocyanine dye that was first introduced to measure blood flow and later recognized as a useful compound for liver function testing (5).…”

“…ICG is a tricarbocyanine dye that was first introduced to measure blood flow and later recognized as a useful compound for liver function testing (5). 99m Tc-mebrofenin and ICG, both organic anions, are almost exclusively taken up by the liver and rapidly excreted into the bile without undergoing biotransformation and with no enterohepatic circulation (1,6). Although a similar hepatocellular uptake mechanism has been postulated, we recently demonstrated a significant difference between ICG and 99m Tc-mebrofenin uptake profiles in a rat model of hepatic ischemiareperfusion injury(7), suggesting that the specific hepatic transporters for ICG and 99m Tc-mebrofenin are distinct.…”