99mTc-GSA Scintigraphy with SPECT for Assessment of Hepatic Function and Functional Volume During Liver Regeneration in a Rat Model of Partial Hepatectomy

Small-animal models are crucial to gain insights in the complex recovery mechanisms of liver function during liver regeneration. (99m)Tc-Mebrofenin hepatobiliary scintigraphy (HBS) has been introduced for noninvasive assessment of liver function in the clinical setting as well as in experimental research. However, HBS is restricted to planar modalities in small animals because hepatic kinetics are generally too fast for SPECT acquisition. (99m)Tc-DTPA-galactosyl serum albumin (where DTPA is diethylenetriaminepentaacetic acid) ((99m)Tc-GSA) scintigraphy is an alternative, receptor-mediated, noninvasive liver function test. After hepatic uptake, (99m)Tc-GSA remains trapped in the liver, which readily enables additional SPECT for the assessment of both liver function and liver functional volume within one test. In this study we evaluated the use of (99m)Tc-GSA scintigraphy combined with SPECT for the assessment of liver function and liver functional volume in normal and regenerating rat livers. The reproducibility of (99m)Tc-GSA scintigraphy and SPECT was investigated by repeated measurements within the same rat. For the assessment in a regenerating liver, (99m)Tc-GSA scintigraphy with SPECT was performed on 1, 3, 5, and 7 d (n = 6 rats per time point) after 70% partial hepatectomy (PH). The correlation between repeated (99m)Tc-GSA measurements was strong (r = 0.75, P = 0.019). In normal rat livers, there was a strong, significant correlation between liver functional volume and conventional liver volume (r = 0.93; < 0.0001). The correlation between (99m)Tc-GSA uptake and liver volume was moderate (r = 0.62, P = 0.043). During the regeneration process, (99m)Tc-GSA uptake was significantly lower compared with both liver volume (P < 0.001) and liver functional volume (P < 0.001), when expressed as a percentage of baseline levels. There was a strong correlation between liver functional volume and conventional liver volume in the regenerating liver (r = 0.92, P < 0.0001). (99m)Tc-GSA scintigraphy combined with SPECT is a feasible, noninvasive method to assess hepatic functional volume in normal rat liver as well as in the regenerating rat liver. However, the hepatic (99m)Tc-GSA uptake as a liver function test seems to underestimate hepatic regeneration in comparison to liver volume.