Imaging Pancreas in Healthy and Diabetic Rodent Model Using [<sup>18</sup>F]Fallypride Positron Emission Tomography/Computed Tomography

Garcia, Adriana; Venugopal, Archana; Pan, Min

doi:10.1089/dia.2014.0041

Cited by 12 publications

(14 citation statements)

References 10 publications

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“…In agreement with studies suggesting the feasibility of targeting DRs for imaging BCM (15,16,19), promising results were obtained for 1 of the 3 DR radioligands. 11 C-(1)-PHNO demonstrated the greatest uptake and contrast compared with background organs in HCs.…”

Section: Discussionsupporting

confidence: 85%

“…Using the 3 dopaminergic radioligands in our study, we can indirectly infer mechanisms of both D 2 and D 3 receptors. On the basis of preliminary success with D 2 receptor radioligands to differentiate healthy and diabetic rats (15,16), and the b-cell gene atlas data (Table 2), D 2 receptors may exist throughout the endocrine and exocrine pancreas. D 2 receptors, as measured by 11 C-(1)-PHNO, may not be directly or linearly correlated with b-cells; therefore, information obtained by this imaging technique should be viewed with caution.…”

Section: Discussionmentioning

confidence: 99%

“…Previous PET studies have attempted to measure BCM by targeting receptors specific to the endocrine pancreas (7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Two radioligands with promising results were 18 F-FP-(1)-dihydrotetrabenazine (DTBZ), which targets vesicular monoamine transporter 2 (VMAT2) and colocalizes with insulin secretory vesicles (7)(8)(9)11), and 11 C-5hydroxytryptophan (5HTP), a precursor of serotonin present in b-cells that may be involved in insulin secretion (10,12,14).…”

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confidence: 99%

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Evaluation of PET Brain Radioligands for Imaging Pancreatic β-Cell Mass: Potential Utility of ¹¹C-(+)-PHNO

et al. 2018

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Type 1 diabetes mellitus (T1DM) is characterized by a loss of β-cells in the islets of Langerhans of the pancreas and subsequent deficient insulin secretion in response to hyperglycemia. Development of an in vivo test to measure β-cell mass (BCM) would greatly enhance the ability to track diabetes therapies. β-cells and neurologic tissues have common cellular receptors and transporters, therefore, we screened brain radioligands for their ability to identify β-cells. We examined a β-cell gene atlas for endocrine pancreas receptor targets and cross-referenced these targets with brain radioligands that were available at our institution. Twelve healthy control subjects and 2 T1DM subjects underwent dynamic PET/CT scans with 6 tracers. The D/D receptor agonist radioligand C-(+)-4-propyl-9-hydroxynaphthoxazine (PHNO) was the only radioligand to demonstrate sustained uptake in the pancreas with high contrast versus abdominal organs such as the kidneys, liver, and spleen, based on the first 30 min of data. Mean SUV from 20 to 30 min demonstrated high uptake ofC-(+)-PHNO in healthy controls (SUV, 13.8) with a 71% reduction in a T1DM subject with undetectable levels of C-peptide (SUV, 4.0) and a 20% reduction in a T1DM subject with fasting C-peptide level of 0.38 ng/mL (SUV, 11.0). SUV in abdominal organs outside the pancreas did not show measurable differences between the control and T1DM subjects, suggesting that the changes in SUV of C-(+)-PHNO may be specific to changes in the pancreas between healthy controls and T1DM subjects. When D and D antagonists were used in nonhuman primates, specific pancreatic binding (SUVR-1) of C-PHNO was reduced by 57% and 38%, respectively.C-(+)-PHNO is a potential marker of BCM, with 2:1 binding of D receptors over D receptors. Further in vitro and in vivo studies to establish D/D receptor specificity to β-cells is warranted to characterize C-(+)-PHNO as a candidate for clinical measurement of BCM in healthy control and diabetic subjects.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Evaluation of PET Brain Radioligands for Imaging Pancreatic β-Cell Mass: Potential Utility of ¹¹C-(+)-PHNO

et al. 2018

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“…In 2005, this hypothesis was proven when Rubi et al showed excellent co‐localization of D2 receptor expression and insulin expression in human and rodent islets . Ever since, the presence of these receptors has been exploited for imaging of insulinomas, congenital hyperinsulinism and islets, both in the pancreas and after transplantation, using [ 18 F]‐L‐3,4‐dihydroxyphenylalanine ([ 18 F]‐DOPA) and [ 18 F]fallypride Positron Emission Tomography (PET) …”

Section: Introductionmentioning

confidence: 99%

Quantitative and longitudinal imaging of intramuscular transplanted islets of Langerhans with SPECT using [¹²³I]IBZM

Willekens

Kroon

Bos

et al. 2017

Diabetes Obesity Metabolism

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A non-invasive imaging method to monitor islet grafts could provide novel and improved insight into the fate of transplanted islets and, potentially, monitor the effect of therapeutic interventions. Therefore, such an imaging method could help improve long-term transplantation outcome. Here, we investigated the use of [ I]IBZM for insulin positive graft volume quantification and longitudinal graft monitoring. SPECT images were acquired 6 weeks after islet transplantation in the calf muscle of rats. For longitudinal graft analysis, rats were monitored by SPECT for 10 weeks. After animals were euthanized, graft containing muscles were dissected for ex vivo analysis and insulin-positive graft volume determination. Six weeks after transplantation, a clear signal was observed in all grafts by SPECT imaging. Moreover, the intensity of the SPECT signal correlated linearly with insulin-positive graft volume, as determined histologically. Longitudinal graft follow-up showed a clear SPECT signal of the transplant from 3 until 10 weeks after transplantation. In this study, we demonstrate for the first time the successful application of a radiotracer, [ I]IBZM, for non-invasive, in vivo graft volume quantification and longitudinal graft monitoring.

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“…More recently, dopamine receptors in the pancreas have been studied as potential surrogate markers for tracking insulin-secreting islet cells in the pancreas or in transplanted islet cells (Garcia et al, 2011, 2014). The presence of D2-like receptors in the intestines has been reported to affect motility in mice (Liz et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Spinal cord dopamine D2/D3 receptors: in vivo and ex vivo imaging in the rat using 18F/11C-fallypride

Kaur

Khararjian

Coleman

et al. 2014

Nuclear Medicine and Biology

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Objectives Spinal cord is known to be innervated with dopaminergic cells with catecholaminergic projections arising from the medulla and pons and dopaminergic transmission in the spinal cord is vital for sensory and motor function. Our goal was to evaluate and compare the imaging capability of dopamine D2/D3 receptors in the rat spinal cord using PET ligands 18F-fallypride and 11C-fallypride. Methods Male Sprague-Dawley rats were used in all in vitro and in vivo studies. Spinal cord and brain sections were used for in vitro autoradiography and ex vivo autoradiography. For in vivo studies animals received a 18F-fallypride scan or a 11C-fallypride PET scan. The spinal cord and the brain were then harvested, flash-frozen and imaged ex vivo. For in vivo analysis Logan plots with cerebellum as a reference was used to evaluate binding potentials (BP). Tissue ratios were used for ex vivo analysis. Drug effects were evaluated using clozapine, haloperidol and dopamine were evaluated on spinal cord sections in vitro. Results In vitro studies showed 18F-fallypride binding to superficial dorsal horn (SDH), dorsal horn (DH), ventral horn (VH) and the pars centralis (PC). In the cervical section, the greatest amount of binding appeared to be in the SDH. Ex vivo studies showed approximately 6% of 18F-fallypride in SDH compared to that observed in the striatum. In vivo analysis of both 18F-fallypride and 11C-fallypride in the spinal cord were comparable to that in the extrastriatal regions. Haloperidol and clozapine displaced more than 75% of the 18F-fallypride in spinal cord sections. Conclusions Our studies showed 18F-fallypride and 11C-fallypride binding in the spinal cord in vitro and in vivo. The binding pattern correlates well with the known distribution of dopamine D2/D3 receptors in the spinal cord.

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Imaging Pancreas in Healthy and Diabetic Rodent Model Using [¹⁸F]Fallypride Positron Emission Tomography/Computed Tomography

Cited by 12 publications

References 10 publications

Evaluation of PET Brain Radioligands for Imaging Pancreatic β-Cell Mass: Potential Utility of ¹¹C-(+)-PHNO

Evaluation of PET Brain Radioligands for Imaging Pancreatic β-Cell Mass: Potential Utility of ¹¹C-(+)-PHNO

Quantitative and longitudinal imaging of intramuscular transplanted islets of Langerhans with SPECT using [¹²³I]IBZM

Spinal cord dopamine D2/D3 receptors: in vivo and ex vivo imaging in the rat using 18F/11C-fallypride

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Imaging Pancreas in Healthy and Diabetic Rodent Model Using [18F]Fallypride Positron Emission Tomography/Computed Tomography

Cited by 12 publications

References 10 publications

Evaluation of PET Brain Radioligands for Imaging Pancreatic β-Cell Mass: Potential Utility of 11C-(+)-PHNO

Evaluation of PET Brain Radioligands for Imaging Pancreatic β-Cell Mass: Potential Utility of 11C-(+)-PHNO

Quantitative and longitudinal imaging of intramuscular transplanted islets of Langerhans with SPECT using [123I]IBZM

Spinal cord dopamine D2/D3 receptors: in vivo and ex vivo imaging in the rat using 18F/11C-fallypride

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Product

Resources

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Imaging Pancreas in Healthy and Diabetic Rodent Model Using [¹⁸F]Fallypride Positron Emission Tomography/Computed Tomography

Evaluation of PET Brain Radioligands for Imaging Pancreatic β-Cell Mass: Potential Utility of ¹¹C-(+)-PHNO

Evaluation of PET Brain Radioligands for Imaging Pancreatic β-Cell Mass: Potential Utility of ¹¹C-(+)-PHNO

Quantitative and longitudinal imaging of intramuscular transplanted islets of Langerhans with SPECT using [¹²³I]IBZM