Novel PET imaging could improve care of patients with diabetes

The researchers have developed a new positron emission tomography (PET) imaging method that could measure beta-cell mass (BCM) and aid in the ability to guide and monitor diabetes therapies. The new nuclear medicine test would be thus beneficial in improving the care of patients with type 1 diabetes. Findings of the study are published in The Journal of Nuclear Medicine.

"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," explain the authors.

"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 a 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."

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β-cells and neurologic tissues have common cellular receptors and transporters, therefore Jason Bini, PET Center, Yale University School of Medicine, New Haven, Connecticut, and colleagues screened brain radioligands for their ability to identify β-cells.

For the study, the researchers examined a β-cell gene atlas for endocrine pancreas receptor targets and cross-referenced these targets with brain radioligands. 12 healthy control subjects and 2 T1DM subjects underwent dynamic PET/CT scans with 6 tracers.

Key Findings:

• 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.


• Mean SUV from 20 to 30 min demonstrated high uptake of ¹¹C-(+)-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 ¹¹C-(+)-PHNO may be specific to changes in the pancreas between healthy controls and T1DM subjects.


• When D₃ and D₂ antagonists were used in nonhuman primates, specific pancreatic binding (SUVR-1) of ¹¹C-PHNO was reduced by 57% and 38%, respectively.

"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," concluded the authors.