Strengths and limitations of using ¹⁸fluorine-fluorodihydroxyphenylalanine PET/CT for congenital hyperinsulinism

Abstract

¹⁸fluorine-fluorodihydroxyphenylalanine (FDOPA) PET/CT is currently the first-line imaging technique to distinguish between focal and diffuse forms of congenital hyperinsulinism (CHI) and to accurately localize focal forms. However, this technique has a number of limitations, mainly the very small size of focal forms or inversely a very large focal form mimicking a diffuse form, and misinterpretation of physiologic uptake masking hot spots or inversely mimicking focal forms. The other limitation is the limited availability of the radiopharmaceutical. FDOPA PET/CT has no recognized competitor to date among the available morphologic and functional imaging techniques. Other potential approaches using specific tracers for positron emission tomography (PET) are discussed, using radiopharmaceuticals specific for β cell mass or targeting somatostatin receptors. These radiopharmaceuticals can be labeled with gallium-68, a PET emitter readily available in PET centers equipped with 68Ge/68Ga generators.

Keywords::

• β-cell mass
• congenital hyperinsulinism
• contrast enhanced CT
• FDOPA
• PET/CT

Financial & competing interests disclosure

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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• To distinguish between focal and diffuse form of CHI is crucial as focal forms can be cured by limited pancreatectomy. In contrast, diffuse forms refractory to medical therapy require near-total pancreatectomy, associated with a high risk of iatrogenic diabetes and/or exocrine pancreas insufficiency.

• At the present time, ¹⁸fluorine-fluorodihydroxyphenylalanine (FDOPA) PET is the best imaging technique in CHI. In a recent meta-analysis, the reported sensitivity and specificity of FDOPA PET/CT to discriminate between focal and diffuse CHI were 89 and 98%, respectively, and the reported accuracy to detect a focal lesion at the correct site was 80%.

• The limitations of FDOPA PET/CT are very small focal forms or, inversely, large focal forms mimicking a diffuse form and misinterpretation of physiologic biliary and urinary uptakes masking hot spots or mimicking focal forms.

• FDOPA is a radiopharmaceutical reflecting DOPA decarboxylase activity of neuroendocrine cells, but is not specific to β cells.

• A promising tracer for PET imaging could be a glucagon-like peptide 1 antagonist (exendin) that binds to glucagon-like peptide 1 receptors and which appears to be specifically expressed by β cells. Exendin PET has been shown to be effective in a few preliminary reports to assess residual β cell mass in patients with diabetes and to localize insulinomas in adult patients. However, it must be remembered that insulinoma and CHI are two different diseases and that the results obtained in insulinomas cannot be extrapolated to CHI.

• The potential role of somatostatin receptor PET has not yet been established in CHI.

• A drawback of FDOPA is its cost and limited availability. The positron emitter Gallium-68 (used to label exendin and somatostatin analogs) is readily available from a generator, independently of a cyclotron. Evaluation of alternative techniques such as exendin PET and/or somatostatin receptor PET is expected in the next few years.

• The development of intraoperative high-resolution ultrasound as a complement to preoperative functional imaging is also expected to help the surgeon to determine the size, configuration and topography of focal CHI.