RT Journal Article
SR Electronic
T1 PET Imaging of Pancreatic Dopamine D<sub>2</sub> and D<sub>3</sub> Receptor Density with <sup>11</sup>C-(+)-PHNO in Type 1 Diabetes
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 570
OP 576
DO 10.2967/jnumed.119.234013
VO 61
IS 4
A1 Jason Bini
A1 Elizabeth Sanchez-Rangel
A1 Jean-Dominique Gallezot
A1 Mika Naganawa
A1 Nabeel Nabulsi
A1 Keunpoong Lim
A1 Soheila Najafzadeh
A1 Anupama Shirali
A1 Jim Ropchan
A1 David Matuskey
A1 Yiyun Huang
A1 Kevan C. Herold
A1 Paul E. Harris
A1 Robert S. Sherwin
A1 Richard E. Carson
A1 Gary W. Cline
YR 2020
UL http://jnm.snmjournals.org/content/61/4/570.abstract
AB 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 D2 and D3 receptor agonist 3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol (11C-(+)-PHNO) to differentiate between healthy control (HC) and T1DM individuals. Methods: 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. Results: 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; P = 0.03). Age at diagnosis correlated significantly with pancreas SUVR-1 (20–30 min) (R2 = 0.67, P = 0.025). Duration of diabetes did not significantly correlate with pancreas SUVR-1 (20–30 min) (R2 = 0.36, P = 0.16). Mean acute C-peptide response to arginine at maximal glycemic potentiation did not significantly correlate with SUVR-1 (20–30 min) (R2 = 0.57, P = 0.05), nor did mean baseline proinsulin (R2 = 0.45, P = 0.10). Immunohistochemistry demonstrated colocalization of dopamine D3 receptor and dopamine D2 receptor in HCs. No colocalization of the dopamine D3 receptor or dopamine D2 receptor was seen with somatostatin, glucagon, or polypeptide Y. In a separate T1DM individual, no immunostaining was seen with dopamine D3 receptor, dopamine D2 receptor, or insulin antibodies, suggesting that loss of endocrine dopamine D3 receptor and dopamine D2 receptor expression accompanies loss of β-cell functional insulin secretory capacity. Conclusion: Thirty-minute scan durations and SUVR-1 provide quantitative outcome measures for 11C-(+)-PHNO, a dopamine D3 receptor–preferring agonist PET radioligand, to differentiate BCM in T1DM and HCs.