Recent advances in PET probes for hepatocellular carcinoma characterization

ABSTRACT

Introduction: Positron Emission Tomography (PET) with ¹⁸F-fluorodeoxyglucose (FDG) presents some limitations for imaging of hepatocellular carcinoma (HCC), the most common primary hepatic malignancy.

Areas covered: The authors discuss the accuracy and limitations of FDG for HCC detection. Then, authors examine the recent advances in PET tracers other than FDG for the biological and prognostic characterization of HCC such as ¹¹C-acetate, ¹¹C-choline, and its ¹⁸F-labeled derivatives.

Expert commentary: FDG PET can be helpful for the identification of the more aggressive and poorly differentiated HCC. ¹¹C-acetate is readily incorporated into intracellular phosphatidylcholine membranes and proved useful for the in vivo biological characterization of the more differentiated and less aggressive HCC. Nevertheless, the short half-life of ¹¹C- radionuclide limits the clinical application of this compound. ¹¹C-choline, another surrogate biomarker of cell membrane biosynthesis, has been demonstrated effective for HCC imaging. The availability of choline derivatives labeled with ¹⁸F-radionuclide (i.e. ¹⁸F-fluoroethylcholine, ¹⁸F-fluorocholine) has overcome the drawbacks due to ¹¹C, thus triggering the clinical applications of choline PET for HCC diagnosis and management. Further research needs to be conducted to better define the alternative or complementary role of these PET probes for the characterization of HCC, with particular regard to the dual-tracer PET-CT modality.

KEYWORDS:

• Hepatocellular carcinoma
• positron emission tomography
• probes
• FDG
• ¹¹C-acetate
• choline

Article Highlights

• In the majority of cases, diagnosis of hepatocellular carcinoma (HCC) is based on CT or MRI findings and biopsy is not performed.

• The aforementioned diagnostic approach leads to a lack of information regarding the biological characteristics of tumor.

• Although PET scan with FDG is not recommended for the detection of HCC due to its low sensitivity, highly increased incorporation of FDG within HCC resulted to be indicative of biological aggressiveness and has been associated with poor outcome after treatments.

• PET with ¹¹C-acetate, a precursor for phospholipid synthesis, presents higher sensitivity for HCC detection and resulted particularly useful for monitoring the response of tumors submitted to loco-regional therapies.

• The short half-life of ¹¹C radionuclide limits the use of ¹¹C-acetate to PET centres with an on-site cyclotron.

• PET with ¹¹C-choline, another precursor for cell membrane synthesis, proved useful for the imaging and the therapeutic management of HCC patients. The introduction of ¹⁸F-labelled choline-derivatives has overcome the limitations due to ¹¹C-half life.

• Since the more aggressive HCC are usually FDG avid, while the more differentiated forms are well visualized with choline or acetate, dual-tracer PET with FDG/¹¹C-acetate or FDG/choline has been proposed as a surrogate imaging biomarker of HCC differentiation.

• Further studies with larger series are needed to better define the clinical impact of dual-tracer PET modality in patients affected by HCC, also taking into account its dosimetric considerations.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.