Pancreatic uptake and radiation dosimetry of 6-[18F]fluoro-L-DOPA from PET imaging studies in infants with congenital hyperinsulinism

Garg, Pradeep; Lokitz, Stephen J.; Truong, Lisa; Putegnat, Burton; Reynolds, Courtney; Rodríguez, L Piqueras; Nazih, Rachid; Nedrelow, Jonathan; Guardia, Miguel de la; Uffman, John; Garg, Sudha; Thornton, Paul

doi:10.1371/journal.pone.0186340

Cited by 15 publications

(14 citation statements)

References 34 publications

(44 reference statements)

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“…Therefore, this technique has radically changed the surgical approach to patients with medically unresponsive HH [102,104]. A dosimetry study of 18F-DOPA derived from the PET-CT images in ten infants (median age 4.84 weeks) with HH suggested that a modest radiation dose (0.30 ± 0.04 mSv/MBq) was adequate [105]. However, there have been recent reports of its inaccuracy in precisely detecting focal lesions [106,107].…”

Section: The Role Of Real-time Continuous Glucose Monitoring (Cgm)mentioning

confidence: 99%

Hyperinsulinemic hypoglycemia in children and adolescents: Recent advances in understanding of pathophysiology and management

Güemes

Rahman

Kapoor

et al. 2020

Rev Endocr Metab Disord

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Hyperinsulinemic hypoglycemia (HH) is characterized by unregulated insulin release, leading to persistently low blood glucose concentrations with lack of alternative fuels, which increases the risk of neurological damage in these patients. It is the most common cause of persistent and recurrent hypoglycemia in the neonatal period. HH may be primary, Congenital HH (CHH), when it is associated with variants in a number of genes implicated in pancreatic development and function. Alterations in fifteen genes have been recognized to date, being some of the most recently identified mutations in genes HK1, PGM1, PMM2, CACNA1D, FOXA2 and EIF2S3. Alternatively, HH can be secondary when associated with syndromes, intra-uterine growth restriction, maternal diabetes, birth asphyxia, following gastrointestinal surgery, amongst other causes. CHH can be histologically characterized into three groups: diffuse, focal or atypical. Diffuse and focal forms can be determined by scanning using fluorine-18 dihydroxyphenylalanine-positron emission tomography. Newer and improved isotopes are currently in development to provide increased diagnostic accuracy in identifying lesions and performing successful surgical resection with the ultimate aim of curing the condition. Rapid diagnostics and innovative methods of management, including a wider range of treatment options, have resulted in a reduction in co-morbidities associated with HH with improved quality of life and long-term outcomes. Potential future developments in the management of this condition as well as pathways to transition of the care of these highly vulnerable children into adulthood will also be discussed.

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Section: The Role Of Real-time Continuous Glucose Monitoring (Cgm)mentioning

confidence: 99%

Hyperinsulinemic hypoglycemia in children and adolescents: Recent advances in understanding of pathophysiology and management

Güemes

Rahman

Kapoor

et al. 2020

Rev Endocr Metab Disord

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“…This in turn induces the expression of insulin-like growth factor 2, inhibits the tumor suppressor genes H19 and cyclin-dependent kinase inhibitor 1C and leads to β-cell proliferation ( 173 ). 18 F-DOPA-PET scanning is currently the only diagnostic imaging tool to accurately localize focal lesions ( 174 ). Pancreatic islets are able to uptake L-DOPA and convert it to dopamine through DOPA decarboxylase.…”

Section: Introductionmentioning

confidence: 99%

Congenital Hyperinsulinism: Diagnosis and Treatment Update

Demirbilek¹,

Hussain²

2018

Jcrpe

105

112

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Pancreatic β-cells are finely tuned to secrete insulin so that plasma glucose levels are maintained within a narrow physiological range (3.5-5.5 mmol/L). Hyperinsulinaemic hypoglycaemia (HH) is the inappropriate secretion of insulin in the presence of low plasma glucose levels and leads to severe and persistent hypoglycaemia in neonates and children. Mutations in 12 different key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A, HNF1A, HK1, PGM1 and PMM2) that are involved in the regulation of insulin secretion from pancreatic β-cells have been described to be responsible for the underlying molecular mechanisms leading to congenital HH. In HH due to the inhibitory effect of insulin on lipolysis and ketogenesis there is suppressed ketone body formation in the presence of hypoglycaemia thus leading to increased risk of hypoglycaemic brain injury. Therefore, a prompt diagnosis and immediate management of HH is essential to avoid hypoglycaemic brain injury and long-term neurological complications in children. Advances in molecular genetics, imaging techniques (18F-DOPA positron emission tomography/computed tomography scanning), medical therapy and surgical advances (laparoscopic and open pancreatectomy) have changed the management and improved the outcome of patients with HH. This review article provides an overview to the background, clinical presentation, diagnosis, molecular genetics and therapy in children with different forms of HH.

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“…The estimated total effective dose in newborns was 2.3 6 0.3 mSv/20 MBq, which is the dose given to children with a body weight under 12.5 kg. This effective dose is significantly higher than in adults but still nearly 4-fold lower than the effective dose reported for the standard PET tracer currently used to diagnose congenital hyperinsulinism in newborns-18 F-DOPA 6-18 F-fluoro-L-3,4-dihydroxyphenylalanine-which is 0.4 6 0.04 mSv/MBq, resulting in a total dose of 8 6 0.8 mSv/20 MBq (19).…”

Section: Discussionmentioning

confidence: 78%

PET-Based Human Dosimetry of ⁶⁸Ga-NODAGA-Exendin-4, a Tracer for β-Cell Imaging

et al. 2019

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68 Ga-NODAGA-exendin-4 is a promising tracer for β-cell imaging using PET/CT. Possible applications include preoperative visualization of insulinomas and discrimination between focal and diffuse forms of congenital hyperinsulinism. There is also a significant role for this tracer in extending our knowledge on the role of β-cell mass in the pathophysiology of type 1 and type 2 diabetes by enabling noninvasive quantification of tracer uptake as a measure for β-cell mass. Calculating radiation doses from this tracer is important to assess its safety for use in patients (including young children) with benign diseases and healthy individuals. Methods: Six patients with hyperinsulinemic hypoglycemia were included. After intravenous injection of 100 MBq of the tracer, 4 successive PET/CT scans were obtained at 30, 60, 120, and 240 min after injection. Tracer activity in the pancreas, kidneys, duodenum, and remainder of the body were determined, and time-integrated activity coefficients for the measured organs were calculated. OLINDA/EXM software, version 1.1, was applied to calculate radiation doses using the reference adult male and female models and to estimate radiation doses to children. Results: The mean total effective dose for adults was very low (0.71 ± 0.07 mSv for a standard injected dose of 100 MBq). The organ with the highest absorbed dose was the kidney (47.3 ± 10.2 mGy/100 MBq). The estimated effective dose was 2.32 ± 0.32 mSv for an injected dose of 20 MBq in newborns. This dose decreased to 0.77 ± 0.11 mSv/20 MBq for 1-y-old children and 0.59 ± 0.05 mSv for an injected dose of 30 MBq in 5-y-old children. Conclusion: Our human PET/CT-based dosimetric calculations show that the effective radiation doses from the novel tracer 68 Ga-NODAGA-exendin-4 are very low for adults and children. The doses are lower than reported for other polypeptide tracers such as somatostatin analogs (2.1-2.6 mSv/100 MBq) and are beneficial for application as a research tool, especially when repeated examinations are needed.

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Pancreatic uptake and radiation dosimetry of 6-[18F]fluoro-L-DOPA from PET imaging studies in infants with congenital hyperinsulinism

Cited by 15 publications

References 34 publications

Hyperinsulinemic hypoglycemia in children and adolescents: Recent advances in understanding of pathophysiology and management

Hyperinsulinemic hypoglycemia in children and adolescents: Recent advances in understanding of pathophysiology and management

Congenital Hyperinsulinism: Diagnosis and Treatment Update

PET-Based Human Dosimetry of ⁶⁸Ga-NODAGA-Exendin-4, a Tracer for β-Cell Imaging

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Pancreatic uptake and radiation dosimetry of 6-[18F]fluoro-L-DOPA from PET imaging studies in infants with congenital hyperinsulinism

Cited by 15 publications

References 34 publications

Hyperinsulinemic hypoglycemia in children and adolescents: Recent advances in understanding of pathophysiology and management

Hyperinsulinemic hypoglycemia in children and adolescents: Recent advances in understanding of pathophysiology and management

Congenital Hyperinsulinism: Diagnosis and Treatment Update

PET-Based Human Dosimetry of 68Ga-NODAGA-Exendin-4, a Tracer for β-Cell Imaging

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PET-Based Human Dosimetry of ⁶⁸Ga-NODAGA-Exendin-4, a Tracer for β-Cell Imaging