August 2, 2018
RESTON, VA – Researchers have discovered a new nuclear medicine test that could improve care of patients with type 1 diabetes. The new positron emission tomography (PET) imaging method could measure beta-cell mass, which would greatly enhance the ability to monitor and guide diabetes therapies. This study is reported in the featured article of the month in The Journal of Nuclear Medicine’s August issue.
According to the American Diabetes Association, approximately 1.25 million American children and adults have type 1 diabetes. Jason Bini, PhD, at the Yale University PET Center in New Haven, Connecticut, explains the significance to patients of being able to track their beta-cell mass:
“Beta-cell mass includes both functional and non-functional beta cells. Many indirect methods to measure beta-cell function are influenced by factors such as glucose and insulin levels and are not able to measure non-functional (dormant) beta cells that may be responsive to treatments. This work is important for patients because uptake of a radiotracer measured on a PET scan could guide treatment options. For example, if a patient has low beta-cell function with high signal in the PET scan, this could represent a patient with dormant beta cells that could respond to a treatment targeting existing cells. If a patient has low beta-cell function and low signal in the PET scan (very few viable or dormant beta cells present), that individual may be a candidate for beta-cell transplantation.”
Beta cells and neurological tissues have common cellular receptors and transporters, so, the Yale researchers screened brain radioligands for their ability to identify beta cells. Then, 12 healthy control subjects and two subjects with type 1 diabetes mellitus underwent dynamic PET/CT scans with six tracers.
The dopamine type 2/type 3 (D2/D3)-receptor agonist radioligand carbon-11 (11C)-(+)-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.
The results provide preliminary evidence that 11C-(+)-PHNO is a potential marker of beta-cell mass with 2:1 binding of D3 receptors over D2 receptors. While further research is needed before clinical application, 11C-(+)-PHNO is a promising way to differentiate the beta-cell mass of healthy individuals from those with type 1 diabetes mellitus, as well as track and guide therapies for diabetes patients.
Bini also points out, “These findings could facilitate development and wider dissemination of novel imaging methods in molecular imaging and nuclear medicine to assess receptor/enzyme pharmacology in diabetes and other endocrine disorders.”
FIGURE: Top: Representative axial slices of PET/CT overlay of pancreas uptake (white arrows) for each dopaminergic radioligand A) 11C-(+)-PHNO B) 11C-FLB457 and C) 11C-raclopride. All SUV images summed from 20-30 minutes. Bottom: Representative coronal PET/CT images of 11C-(+)-PHNO in pancreas (white arrows) for A) healthy control B) C-peptide deficient T1DM subject C) T1DM subject with detectable C-peptide All SUV images are summed from 20-30 minutes. A) SUV scale 0-20 B-C) SUV scale 0-15. Credit: J Bini et al., Yale University, New Haven, CT.
Authors of “Evaluation of PET Brain Radioligands for Imaging Pancreatic β-Cell Mass: Potential Utility of 11C-(+)-PHNO” include Jason Bini, Mika Naganawa, Nabeel Nabulsi, Yiyun Huang, Jim Ropchan, Keunpoong Lim, Soheila Najafzadeh, Kevan C. Herold, Gary W. Cline, and Richard E. Carson, Yale University, New Haven, Connecticut.
This study was supported by National Institutes of Health (NIH) grant 1DP3DK104092-01 and was also made possible by NIH grant 1S10OD010322-01 and by Clinical and Translational Science Awards (CTSA) grant UL1 TR000142 from the National Center for Advancing Translational Sciences (NCATS) at NIH.
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