On the use of [18F]DOPA as an imaging biomarker for transplanted islet mass

Aim

Islet transplantation is being developed as a potential cure for patients with type 1 diabetes. There is a need for non-invasive imaging techniques for the quantification of transplanted islets, as current transplantation sites are associated with a substantial loss of islet viability. The dopaminergic metabolic pathway is present in the islets; therefore, we propose Fluorine-18 labeled l-3,4-dihydroxyphenylalanine (¹⁸F]DOPA) as a biomarker for transplanted islet mass.

Methods

The expression of enzymes involved in the dopaminergic metabolic pathway was investigated in both native and transplanted human islets. The specific uptake of ¹⁸F]DOPA in islets and immortalized beta cells was studied in vitro by selective blocking of dopa decarboxylase (DDC). Initial in vivo PET imaging of viable subcutaneous human islets was performed using ¹⁸F]DOPA.

Results

DDC and vesicular monoamine transporter 2 are co-localized with insulin in the native human pancreas, and the expression is retained after transplantation. Islet uptake of the ¹⁸F]DOPA could be modulated by inhibiting DDC, indicating that the uptake followed the normal dopaminergic metabolic pathway. In vivo imaging revealed ¹⁸F]DOPA uptake at the site of the functional islet graft.

Conclusion

Based on the in vitro and in vivo results presented in this study, we propose to further validate ¹⁸F]DOPA-PET as a sensitive imaging modality for imaging extrahepatically transplanted islets.