Skip to main content

PET Imaging of Pancreatic Dopamine D and D Receptor Density with C-(+)-PHNO in Type 1 Diabetes.

Citation
Bini, J., et al. “Pet Imaging Of Pancreatic Dopamine D And D Receptor Density With C-(+)-Phno In Type 1 Diabetes.”. Journal Of Nuclear Medicine : Official Publication, Society Of Nuclear Medicine, pp. 570-576.
Center Yale University
Author Jason Bini, Elizabeth Sanchez-Rangel, Jean-Dominique Gallezot, Mika Naganawa, Nabeel Nabulsi, Keunpoong Lim, Soheila Najafzadeh, Anupama Shirali, Jim Ropchan, David Matuskey, Yiyun Huang, Kevan C Herold, Paul E Harris, Robert S Sherwin, Richard E Carson, Gary W Cline
Keywords PET, PHNO, diabetes, pancreas, β-cell mass
Abstract

Type 1 diabetes mellitus (T1DM) has traditionally been characterized by a complete destruction of β-cell mass (BCM); however, there is growing evidence of possible residual BCM present in T1DM. Given the absence of in vivo tools to measure BCM, routine clinical measures of β-cell function (e.g., C-peptide release) may not reflect BCM. We previously demonstrated the potential utility of PET imaging with the dopamine D and D receptor agonist 3,4,4a,5,6,10b-hexahydro-2-naphtho[1,2-][1,4]oxazin-9-ol (C-(+)-PHNO) to differentiate between healthy control (HC) and T1DM individuals. Sixteen individuals participated (10 men, 6 women; 9 HCs, 7 T1DMs). The average duration of diabetes was 18 ± 6 y (range, 14-30 y). Individuals underwent PET/CT scanning with a 120-min dynamic PET scan centered on the pancreas. One- and 2-tissue-compartment models were used to estimate pancreas and spleen distribution volume. Reference region approaches (spleen as reference) were also investigated. Quantitative PET measures were correlated with clinical outcome measures. Immunohistochemistry was performed to examine colocalization of dopamine receptors with endocrine hormones in HC and T1DM pancreatic tissue. C-peptide release was not detectable in any T1DM individuals, whereas proinsulin was detectable in 3 of 5 T1DM individuals. Pancreas SUV ratio minus 1 (SUVR-1) (20-30 min; spleen as reference region) demonstrated a statistically significant reduction (-36.2%) in radioligand binding (HCs, 5.6; T1DMs, 3.6; = 0.03). Age at diagnosis correlated significantly with pancreas SUVR-1 (20-30 min) ( = 0.67, = 0.025). Duration of diabetes did not significantly correlate with pancreas SUVR-1 (20-30 min) ( = 0.36, = 0.16). Mean acute C-peptide response to arginine at maximal glycemic potentiation did not significantly correlate with SUVR-1 (20-30 min) ( = 0.57, = 0.05), nor did mean baseline proinsulin ( = 0.45, = 0.10). Immunohistochemistry demonstrated colocalization of dopamine D receptor and dopamine D receptor in HCs. No colocalization of the dopamine D receptor or dopamine D receptor was seen with somatostatin, glucagon, or polypeptide Y. In a separate T1DM individual, no immunostaining was seen with dopamine D receptor, dopamine D receptor, or insulin antibodies, suggesting that loss of endocrine dopamine D receptor and dopamine D receptor expression accompanies loss of β-cell functional insulin secretory capacity. Thirty-minute scan durations and SUVR-1 provide quantitative outcome measures for C-(+)-PHNO, a dopamine D receptor-preferring agonist PET radioligand, to differentiate BCM in T1DM and HCs.

Year of Publication
2020
Journal
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Volume
61
Issue
4
Number of Pages
570-576
Date Published
04/2020
ISSN Number
1535-5667
DOI
10.2967/jnumed.119.234013
Alternate Journal
J. Nucl. Med.
PMID
31601695
PMCID
PMC7198375
Download citation