PET Imaging of Pancreatic Dopamine D2 and D3 Receptor Density with 11C-(+)-PHNO in Type 1 Diabetes

Bini, Jason; Sanchez‐Rangel, Elizabeth; Gallezot, Jean‐Dominique; Naganawa, Mika; Nabulsi, Nabeel; Lim, Keunpoong; Najafzadeh, Soheila; Shirali, Anupama; Ropchan, Jim; Matuskey, David; Huang, Yiyun; Herold, Kevan C.; Harris, Paul E.; Sherwin, Robert S.; Carson, Richard E.; Cline, Gary W.

doi:10.2967/jnumed.119.234013

Cited by 18 publications

(14 citation statements)

References 36 publications

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“…Therefore, the various molecules whose expression is observed specifically in b cells have been explored, and those ligands, substrates, and antibodies have been investigated as putative probes for b-cell imaging. To date, sulfonylurea receptor 1 (SUR1) (40,41), glucose transporter 2 (42), voltage-dependent calcium channel (43), G protein-coupled receptor 44 (GPR44) (44,45), D2 and D3 dopamine receptors (46,47), serotonergic system (48-51), vesicular monoamine transporter 2 (VMAT2) (52,53), and GLP-1 receptor (GLP-1R) (54, 55) have been reported as potential probe targets (Figure 2) (56).…”

Section: Exploration Of Ideal Probe Targets In In Vivo B-cell Imagingmentioning

confidence: 99%

“…D2 and D3 dopamine receptors involve glucose-stimulated insulin secretion in b cells ( 59) and have been suggested as a target for b-cell imaging (46). PET imaging with the receptor agonist 3,4,4a,5,6,10b-hexahydro-2H-naphtho(1,2-b)(1,4) oxazin-9-ol was examined in patients with type 1 diabetes mellitus (46), demonstrating reasonable pancreatic uptake and non-negligible uptake in the spleen, located near the tail of the pancreas. A substantial overlapping of probe accumulations in the pancreas has been observed between patients with type 1 diabetes mellitus and healthy participants (46).…”

Section: Exploration Of Ideal Probe Targets In In Vivo B-cell Imagingmentioning

confidence: 99%

“…PET imaging with the receptor agonist 3,4,4a,5,6,10b-hexahydro-2H-naphtho(1,2-b)(1,4) oxazin-9-ol was examined in patients with type 1 diabetes mellitus (46), demonstrating reasonable pancreatic uptake and non-negligible uptake in the spleen, located near the tail of the pancreas. A substantial overlapping of probe accumulations in the pancreas has been observed between patients with type 1 diabetes mellitus and healthy participants (46). Another probe, [ 18 F]dihydroxyphenylalanine [( 18 F)DOPA], has been investigated for nesidioblastosis, with several groups reporting the successful imaging of responsible foci.…”

Section: Exploration Of Ideal Probe Targets In In Vivo B-cell Imagingmentioning

confidence: 99%

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Non-invasive Beta-cell Imaging: Visualization, Quantification, and Beyond

2021

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Pancreatic beta (β)-cell dysfunction and reduced mass play a central role in the development and progression of diabetes mellitus. Conventional histological β-cell mass (BCM) analysis is invasive and limited to cross-sectional observations in a restricted sampling area. However, the non-invasive evaluation of BCM remains elusive, and practical in vivo and clinical techniques for β-cell-specific imaging are yet to be established. The lack of such techniques hampers a deeper understanding of the pathophysiological role of BCM in diabetes, the implementation of personalized BCM-based diabetes management, and the development of antidiabetic therapies targeting BCM preservation and restoration. Nuclear medical techniques have recently triggered a major leap in this field. In particular, radioisotope-labeled probes using exendin peptides that include glucagon-like peptide-1 receptor (GLP-1R) agonist and antagonist have been employed in positron emission tomography and single-photon emission computed tomography. These probes have demonstrated high specificity to β cells and provide clear images accurately showing uptake in the pancreas and transplanted islets in preclinical in vivo and clinical studies. One of these probes, 111indium-labeled exendin-4 derivative ([Lys12(111In-BnDTPA-Ahx)]exendin-4), has captured the longitudinal changes in BCM during the development and progression of diabetes and under antidiabetic therapies in various mouse models of type 1 and type 2 diabetes mellitus. GLP-1R-targeted imaging is therefore a promising tool for non-invasive BCM evaluation. This review focuses on recent advances in non-invasive in vivo β-cell imaging for BCM evaluation in the field of diabetes; in particular, the exendin-based GLP-1R-targeted nuclear medicine techniques.

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Section: Exploration Of Ideal Probe Targets In In Vivo B-cell Imagingmentioning

confidence: 99%

Section: Exploration Of Ideal Probe Targets In In Vivo B-cell Imagingmentioning

confidence: 99%

Section: Exploration Of Ideal Probe Targets In In Vivo B-cell Imagingmentioning

confidence: 99%

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Non-invasive Beta-cell Imaging: Visualization, Quantification, and Beyond

2021

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“…Insulin regulates DAT and VMAT2 levels through the PI3K/AKT pathway, and insulin deficiency leads to DAT and VMAT2 dysfunction. Dopamine D2 receptors can also regulate DAT and VMAT2 expression through the ERK signaling pathway ( Carvelli et al, 2002 ; Owens et al, 2012 ; Samandari et al, 2013 ; Bini et al, 2019 ).…”

Section: Molecular Genetics Cell Biology and Epidemiology: Correlatmentioning

confidence: 99%

Elucidating the Relationship Between Diabetes Mellitus and Parkinson’s Disease Using 18F-FP-(+)-DTBZ, a Positron-Emission Tomography Probe for Vesicular Monoamine Transporter 2

et al. 2020

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Diabetes mellitus (DM) and Parkinson’s disease (PD) have been and will continue to be two common chronic diseases globally that are difficult to diagnose during the prodromal phase. Current molecular genetics, cell biological, and epidemiological evidences have shown the correlation between PD and DM. PD shares the same pathogenesis pathways and pathological factors with DM. In addition, β-cell reduction, which can cause hyperglycemia, is a striking feature of DM. Recent studies indicated that hyperglycemia is highly relevant to the pathologic changes in PD. However, further correlation between DM and PD remains to be investigated. Intriguingly, polycystic monoamine transporter 2 (VMAT2), which is co-expressed in dopaminergic neurons and β cells, is responsible for taking up dopamine into the presynaptic vesicles and can specifically bind to the β cells. Furthermore, we have summarized the specific molecular and diagnostic functions of VMAT2 for the two diseases reported in this review. Therefore, VMAT2 can be applied as a target probe for positron emission tomography (PET) imaging to detect β-cell and dopamine level changes, which can contribute to the diagnosis of DM and PD during the prodromal phase. Targeting VMAT2 with the molecular probe 18 F-FP-(+)-DTBZ can be an entry point for the β cell mass (BCM) changes in DM at the molecular level, to clarify the potential relationship between DM and PD. VMAT2 has promising clinical significance in investigating the pathogenesis, early diagnosis, and treatment evaluation of the two diseases.

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“…Second, Bini et al acknowledged that the one-tissue-compartment model does not fit the data for t > 60min ( Figure 3) (1). In this connection, we have recently indicated that a previously published method can then be applied to any tracer for assessing its release rate constant (kB) from tissue back to blood at late imaging, that is, when the part of free tracer in blood and interstitial volume plus, possibly, the part of radiolabeled metabolites, have become negligible in the tissue TAC (4).…”

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confidence: 99%

¹¹C-(+)-PHNO Trapping Reversibility for Quantitative PET Imaging of β-Cell Mass in Patients with Type 1 Diabetes

Laffon

Marthan

2020

J Nucl Med

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For efficiently differentiating the pancreas uptake of the dopamine D2/D3-receptor agonist 11 C-(+)-PHNO between healthy controls (HC) and Type-1 diabetes mellitus (T1DM) individuals, Bini et al. recently compared different methods of quantitative PET imaging. These methods involved tissue-compartment model analyses providing the tracer distribution volume (VT), as well as reference-region approaches, which did or did not require arterial sampling, respectively (1). Quantitative parameters were also correlated to clinically relevant measures of beta-cell-mass (BCM) function such as C-peptide, proinsulin, age-at-diagnosis and disease duration. The authors reported a reduction in the 20-30min pancreas/spleen SUV ratio (SUVR-1) of-36.2% between HC and T1DM (p = 0.03), and concluded that SUVR-1 could be used to differentiate BCM in HC and T1DM subjects. We assume that Bini et al.'s study does not take into account the trapping reversibility of 11 C-(+)-PHNO in the pancreas of both HC and T1DM subjects, that could, in addition, be helpful to assess BCM by using data acquired beyond 30min post-injection (p.i.). This assumption is evidenced in the Figure 3 of the paper with representative decay-corrected time-activity curves (TAC) of pancreas (and spleen) acquired over 120min that, clearly, do not reach a plateau at late imaging (1,2).

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PET Imaging of Pancreatic Dopamine D₂ and D₃ Receptor Density with ¹¹C-(+)-PHNO in Type 1 Diabetes

Cited by 18 publications

References 36 publications

Non-invasive Beta-cell Imaging: Visualization, Quantification, and Beyond

Non-invasive Beta-cell Imaging: Visualization, Quantification, and Beyond

Elucidating the Relationship Between Diabetes Mellitus and Parkinson’s Disease Using 18F-FP-(+)-DTBZ, a Positron-Emission Tomography Probe for Vesicular Monoamine Transporter 2

¹¹C-(+)-PHNO Trapping Reversibility for Quantitative PET Imaging of β-Cell Mass in Patients with Type 1 Diabetes

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PET Imaging of Pancreatic Dopamine D2 and D3 Receptor Density with 11C-(+)-PHNO in Type 1 Diabetes

Cited by 18 publications

References 36 publications

Non-invasive Beta-cell Imaging: Visualization, Quantification, and Beyond

Non-invasive Beta-cell Imaging: Visualization, Quantification, and Beyond

Elucidating the Relationship Between Diabetes Mellitus and Parkinson’s Disease Using 18F-FP-(+)-DTBZ, a Positron-Emission Tomography Probe for Vesicular Monoamine Transporter 2

11C-(+)-PHNO Trapping Reversibility for Quantitative PET Imaging of β-Cell Mass in Patients with Type 1 Diabetes

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PET Imaging of Pancreatic Dopamine D₂ and D₃ Receptor Density with ¹¹C-(+)-PHNO in Type 1 Diabetes

¹¹C-(+)-PHNO Trapping Reversibility for Quantitative PET Imaging of β-Cell Mass in Patients with Type 1 Diabetes