The Effect of Fasting on PET Imaging of Hepatocellular Carcinoma

Nathan Tenley, David J. Corn, Lewis Yuan, Zhenghong Lee

Department of Biomedical Engineering, Case Western Reserve University, Cleveland, USA.
Department of Radiology, University Hospitals Case Medical Center, Cleveland, USA..

DOI: 10.4236/jct.2013.42071                

Abstract

The clinical utility of positron emission tomography (PET) imaging for liver cancer applications is not clearly defined either for diagnosis or treatment assessment. Previous clinical studies demonstrated that fluorodeoxyglucose (FDG) did not show uptake in some hepatocellular carcinoma (HCC) while acetate showed uptake. Pre-imaging fasting is required for clinical PET imaging with FDG. No studies were done to confirm the effect of fasting on acetate uptake in HCC for PET imaging. We investigated this situation with a woodchuck model of viral infection-induced HCC. Methods: Four tumor-bearing and one control woodchucks were involved in this study. They were first imaged by PET in fed state followed by another imaging session one week later when they were fasted over-night. Some animals also had FDG- PET scan that was acquired later on the same day. After imaging studies, animals were sacrificed, and their liver excised for histology. Standardized Uptake Value (SUV) was calculated using a region of interest (ROI) placed on each tumor with focal uptake. Results: Acetate showed uptake in each HCC lesion when the animals were either fasted or fed with no significant difference in SUV values (p = 0.177); some of the tumors were histologically confirmed as well-differentiated HCC while others were confirmed as moderately- or poorly-differentiated HCC; no focal uptake was found in the control animal. For the accompanying FDG scans, the uptake was detected only in animals that were fasted although the uptake pattern was different from that with acetate. Conclusion: This study provided a hint that fasting or not has little impact on PET imaging of HCC with acetate. It also confirmed prior finding regarding tumor heterogeneity that led to different tracer uptake pattern in the same tumor. Human studies are needed to validate the findings from this pre-clinical investigation.

Keywords

Acetate; FDG; Hepatocellular Carcinoma; Woodchuck; Positron Emission Tomography

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	M. Yoshimoto, et al., “Characterization of Acetate Metabolism in Tumor Cells in Relation to Cell Proliferation: Acetate Metabolism in Tumor Cells,” Nuclear Medicine and Biology, Vol. 28, No. 2, 2001. pp. 117-122. doi:10.1016/S0969-8051(00)00195-5
[2]	N. Oyama, et al., “11C-Acetate PET Imaging of Prostate Cancer,” Journal of Nuclear Medicine, Vol. 43, No. 2, 2002, pp. 181-186.
[3]	C. L. Ho, et al., “11C-Acetate PET Imaging in Hepatocellular Carcinoma and Other Liver Masses,” Journal of Nuclear Medicine, Vol. 44, No. 2, 2003, pp. 213-221.
[4]	S. Li, et al., “Comparison of (11)C-Acetate Positron Emission Tomography and (67)Gallium Citrate Scintigraphy in Patients with Hepatocellular Carcinoma,” Liver International, Vol. 26, No. 8, 2006, pp. 920-927. doi:10.1111/j.1478-3231.2006.01335.x
[5]	C. L. Ho, et al., “Dual-Tracer PET/CT Imaging in Evaluation of Metastatic Hepatocellular Carcinoma,” Journal of Nuclear Medicine, Vol. 48, No. 6, 2007, pp. 902-909. doi:10.2967/jnumed.106.036673
[6]	J. W. Park, et al., “A Prospective Evaluation of 18F-FDG and 11C-Acetate PET/CT for Detection of Primary and Metastatic Hepatocellular Carcinoma,” Journal of Nuclear Medicine, Vol. 49, No. 12, 2008, pp. 1912-1921. doi:10.2967/jnumed.108.055087
[7]	K. H. Hwang, et al., “Evaluation of Patients with Hepatocellular Carcinomas Using [(11)C]Acetate and [(18)F] FDG PET/CT: A Preliminary Study,” Applied Radiation and Isotopes, Vol. 67, No. 7, 2009, pp. 1195-1198. doi:10.1016/j.apradiso.2009.02.011
[8]	A. M. Gharib, et al., “Molecular Imaging of Hepatocellular Carcinoma,” Gastroenterology, Vol. 127, No. 5, 2004, pp. S153-158. doi:10.1053/j.gastro.2004.09.029
[9]	H. B. El-Serag and A. C. Mason, “Rising Incidence of Hepatocellular Carcinoma in the United States,” The New England Journal of Medicine, Vol. 340, No. 10, 1999, pp. 745-750. doi:10.1056/NEJM199903113401001
[10]	T. Torizuka, et al., “In Vivo Assessment of Glucose Metabolism in Hepatocellular Carcinoma with FDG-PET,” Journal of Nuclear Medicine, Vol. 36, No. 10, 1995, pp. 1811-1817.
[11]	K. H. Lee, et al., “Effects of Anesthetic Agents and Fasting Duration on 18F-FDG Biodistribution and Insulin Levels in Tumor-Bearing Mice,” Journal of Nuclear Medicine, Vol. 46, No. 9, 2005, pp. 1531-1536.
[12]	W. Okumura, et al., “Usefulness of Fasting 18F-FDG PET in Identification of Cardiac Sarcoidosis,” Journal of Nuclear Medicine, Vol. 45, No. 12, 2004, pp. 1989-1998.
[13]	T. Kihlberg, et al., “Synthesis of [1-11C], [2-11C], [1-11C] (2H3) and [2-11C](2H3)Acetate for in Vivo Studies of Myocardium Using PET,” Nuclear Medicine and Biology, Vol. 21, No. 8, 1994, pp. 1067-1072. doi:10.1016/0969-8051(94)90178-3
[14]	M. E. Daube-Witherspoon, et al., “Application of the Row Action Maximum Likelihood Algorithm with Spherical Basis Functions to Clinical PET Imaging,” IEEE Transactions on Nuclear Science, Vol. 48, 2001, pp. 24-30. doi:10.1109/23.910827
[15]	N. Salem, et al., “Quantitative Evaluation of 2-Deoxy-2[18F]fluoro-D-glucose-positron Emission Tomography Imaging on the Woodchuck Model of Hepatocellular Carcinoma with Histological Correlation,” Molecular Imaging and Biology, Vol. 9, No. 3, 2007, pp. 135-143. doi:10.1007/s11307-007-0092-5
[16]	N. Salem, et al., “[(Methyl)1-(11)c]-Acetate Metabolism in Hepatocellular Carcinoma,” Molecular Imaging and Biology, Vol. 13, 2011, pp. 140-151. doi:10.1007/s11307-010-0308-y
[17]	N. Salem, et al., “PET Imaging of Hepatocellular Carcinoma with 2-Deoxy-2[18F]fluoro-D-glucose, 6-Deoxy-6[18F]fluoroD-glucose, [1-11C]-Acetate and [N-methyl-11C]-choline,” The Quarterly Journal of Nuclear Medicine and Molecular Imaging, Vol. 53, No. 2, 2009, pp. 144-156.
[18]	Y. Kuang, et al., “A Colorimetric Assay Method to Measure Acetyl-CoA Synthetase Activity: Application to Woodchuck Model of Hepatitis Virus-Induced Hepatocellular Carcinoma,” Journal of Biochemical and Biophysical Methods, Vol. 70, No. 4, 2007, pp. 649-655. doi:10.1016/j.jbbm.2007.02.008
[19]	B. Alberts, et al., “Cell Chemistry and Biosynthesis,” In: Molecular Biology of the Cell, Garland Science, New York, 2002, pp. 47-109.