florbenazine-f-18 and Diabetes-Mellitus--Type-2

There are presently no reliable ways to quantify human pancreatic beta cell mass (BCM) in vivo, which prevents an accurate understanding of the progressive beta cell loss in diabetes or following islet transplantation. Furthermore, the lack of beta cell imaging hampers the evaluation of the impact of new drugs aiming to prevent beta cell loss or to restore BCM in diabetes. We presently discuss the potential value of BCM determination as a cornerstone for individualized therapies in diabetes, describe the presently available probes for human BCM evaluation, and discuss our approach for the discovery of novel beta cell biomarkers, based on the determination of specific splice variants present in human beta cells. This has already led to the identification of DPP6 and FXYD2ga as two promising targets for human BCM imaging, and is followed by a discussion of potential safety issues, the role for radiochemistry in the improvement of BCM imaging, and concludes with an overview of the different steps from pre-clinical validation to a first-in-man trial for novel tracers.

Topics: 5-Hydroxytryptophan; Animals; Biomarkers; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Exenatide; Fluorine Radioisotopes; Humans; Insulin-Secreting Cells; Islets of Langerhans Transplantation; Magnetic Resonance Imaging; Nerve Tissue Proteins; Positron Emission Tomography Computed Tomography; Potassium Channels; Radiopharmaceuticals; Single-Domain Antibodies; Sodium-Potassium-Exchanging ATPase; Technetium; Tetrabenazine; Tomography, Emission-Computed, Single-Photon

The vesicular monoamine transporter, type 2 (VMAT2) is expressed by insulin producing β cells and was evaluated as a biomarker of β cell mass (BCM) by positron emission tomography (PET) with [(18)F]fluoropropyl-dihydrotetrabenazine ([(18)F]FP-(+)-DTBZ).. We evaluated the feasibility of longitudinal pancreatic PET VMAT2 quantification in the pancreas in two studies of healthy controls and patients with type 1 or 2 diabetes. VMAT2 binding potential (BPND) was estimated voxelwise using a reference tissue method in a cross-sectional study, followed by assessment of reproducibility using a test-retest paradigm. Metabolic function was evaluated by stimulated c-peptide measurements.. Pancreatic BPND was significantly decreased in patients with type 1 diabetes relative to controls and the test-retest variability was 9.4%.. Pancreatic VMAT2 content is significantly reduced in long-term diabetes patients relative to controls and repeat scans are sufficiently reproducible to suggest the feasibility clinically VMAT2 measurements in longitudinal studies of new onset diabetes.

Topics: Adult; Case-Control Studies; Cell Size; Demography; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Fluorine Radioisotopes; Glucose; Humans; Insulin; Insulin-Secreting Cells; Male; Middle Aged; Positron-Emission Tomography; Protein Binding; Tetrabenazine; Vesicular Monoamine Transport Proteins