On the use of [ 18 F]DOPA as an imaging biomarker for transplanted islet mass
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ORIGINAL ARTICLE
On the use of [18F]DOPA as an imaging biomarker for transplanted islet mass Olof Eriksson • Akiva Mintz • Chengyang Liu Ming Yu • Ali Naji • Abass Alavi
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Received: 22 May 2013 / Accepted: 10 October 2013 / Published online: 29 October 2013 Ó The Japanese Society of Nuclear Medicine 2013
Abstract 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.
O. Eriksson and A. Mintz equally contributed to this work. O. Eriksson Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University, Uppsala, Sweden A. Mintz C. Liu M. Yu A. Naji A. Alavi (&) Perelman School of Medicine at the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, USA e-mail: [email protected]
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. Keywords Islet imaging FDOPA Positron emission tomography
Introduction Significant progress has been made in non-invasive imaging and quantification of endogenous and transplanted beta cell mass (BCM) during the last decade [1]. The endocrine pancreas shares many properties with the central nervous system, especially the monoamine signaling pathways. These metabolic pathways, especially the dopaminergic and serotonergic systems, were explored already during the infancy of positron emission tomography (PET) during the 1980s. Today, PET tracers for dopamine (L-3,4-dihydroxyphenylalanine; L-DOPA, [2])and serotonin synthesis (5-hydroxy-L-tryptophan, 5-HTP [3]) as well as monoamine transport (dihydrotetrabenazine, DTBZ [4]) and degradation [5] are in clinical use. Several of these have been suggested as potential beta cell specific ligands, most notably radiolabeled analogs of the vesicular monoamine transporter 2 (V
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