ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This experimental study used positron emission tomography (PET) as non-invasive method to monitor stem cells-islet grafts. [¹⁸F]exendin and [¹⁸F]FDOPA PET showed potential as non-invasive methods to assess stem cells-islet graft size and aspects of graft composition.

Stem cell-derived islets (SC-islets) are used as an emerging cell replacement therapy for insulin-dependent diabetes (1). Non-invasive long-term monitoring methods for SC-islet grafts are needed to detect potential unwanted expansion and to optimise their effectiveness.

PET has previously been used to monitor transplanted primary islets. Here it was tested as non-invasive way to monitor SC-islet grafts in mice. Different doses of human SC-islets were implanted and the grafts were then monitored with PET using two tracers, glucagon-like peptide 1 receptor-binding [¹⁸F]F-dibenzocyclooctyne-exendin-4 ([¹⁸F]exendin) and the dopamine precursor 6-[¹⁸F]fluoro-l-3,4-dihydroxyphenylalanine ([¹⁸F]FDOPA), for 5 months, followed by histological assessment of graft size and composition.

The study showed a successful application of [¹⁸F]exendin and [¹⁸F]FDOPA PET, which allowed accurate quantification of total SC-islet graft volume. In addition, [¹⁸F]exendin PET enabled assessment of SC-islet graft quality by providing information about graft stem cell-derived β-cell and cyst composition.

These findings are promising, but they need to be replicated and tested in humans. Nevertheless, the study brings hopes that PET imaging might become a tool to improve the safety and efficacy of SC-islet grafts as an emerging cell replacement therapy for type 1 diabetes.

References: 1. Hogrebe NJ, Ishahak M, Millman JR. Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes. Cell Stem Cell. 2023;30(5):530-48.