The effect of fasting on PET Imaging of Hepatocellular Carcinoma

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: FDG; acetate; hepatocellular carcinoma; positron emission tomography; woodchuck.

FIGURE 1

The woodchuck model of HCC was scanned first in fed state (right panel), and then one week later in fasted state (left panel). During each imaging session, a dynamic PET scan of 30 min with [¹¹C]-acetate was performed first, followed by a static PET with FDG, see text. The time activity curves of acetate uptake in liver tumor with focal uptake and the background region were generated (bottom).

FIGURE 2

Comparison between acetate and FDG. Each tracer showed its uptake in different parts of the same tumor with different pathological grades (see text), which is in good agreement with published human study [ref]. Acetate uptake was not affected by the state of fed or fasted, but FDG was affected as anticipated.

FIGURE 3

A schematic diagram of glucose-dependent lipogenesis potentially linking the two pathways affecting FDG and acetate metabolism, see text.

FIGURE 4

Pipelining for dual-tracer imaging. Up to four woodchucks can be placed side-way on the long board of the clinical PET/CT scanner with the liver positioned at the center of FOV. The animals were anesthetized with an intramuscular injection of 5 mg/kg of Xylazine and 50 mg/kg of Ketamine. Thereafter, incremental injections of pentobarbital were used to maintain anesthesia. Gas anesthesia was not used due to arrangement of gas tubing and separate anesthetic maintenance of each animal. Normally, animals were injected with an ¹¹C-labeled tracer and scanned in sequence when the bed position advanced. During this sequential imaging, an ¹⁸F-labeled tracer could be injected into an animal after its ¹¹C scanning. After all ¹¹C scans were finished, the bed returned to the initial position and each animal would be ready for ¹⁸F scanning in sequence, again.