99mTc-GSA Scintigraphy with SPECT for Assessment of Hepatic Function and Functional Volume During Liver Regeneration in a Rat Model of Partial Hepatectomy
Wilmar de Graaf 1,
Reeta L. Veteläinen 1,
Kora de Bruin 2,
Arlène K. van Vliet 1,
Thomas M. van Gulik 1*,
and
Roelof J. Bennink 2
1 Department of Surgery (Surgical Laboratory), Academic Medical Center, Amsterdam, The Netherlands
2 Department of Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands
* To whom correspondence should be addressed. E-mail: t.m.vangulik{at}amc.uva.nl.
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Abstract |
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Small-animal models are crucial to gain insights in the complex recovery mechanisms of liver function during liver regeneration. 99mTc-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. 99mTc-DTPA-galactosyl serum albumin (where DTPA is diethylenetriaminepentaacetic acid) (99mTc-GSA) scintigraphy is an alternative, receptor-mediated, noninvasive liver function test. After hepatic uptake, 99mTc-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 99mTc-GSA scintigraphy combined with SPECT for the assessment of liver function and liver functional volume in normal and regenerating rat livers. Methods: The reproducibility of 99mTc-GSA scintigraphy and SPECT was investigated by repeated measurements within the same rat. For the assessment in a regenerating liver, 99mTc-GSA scintigraphy with SPECT was performed on 1, 3, 5, and 7 d (n = 6 rats per time point) after 70% partial hepatectomy (PH). Results: The correlation between repeated 99mTc-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 99mTc-GSA uptake and liver volume was moderate (r = 0.62, P = 0.043). During the regeneration process, 99mTc-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). Conclusion: 99mTc-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 99mTc-GSA uptake as a liver function test seems to underestimate hepatic regeneration in comparison to liver volume.
Key Words:
liver function, liver functional volume, liver regeneration, 99mTc-GSA scintigraphy
