Novel Use of Agent 11C-PHNO for Pet CT Imaging of Pancreatic Beta-Cell Mass

Abstract

There is growing interest in developing a method to measure pancreatic beta-cell mass (BCM) so as to: 1) monitor progression of beta cell changes in type 1 and type 2 diabetes; 2) identify therapies to preserve, restore or regenerate beta cells; and 3) monitor viability of islets after transplantation therapy. Given that beta cells and neurons have functional similarities, we tested the hypothesis that receptors, transporters, or proteins essential for signal detection and propagation, may be common to both cell types. Hence, we assessed if Positron Emission Tomography (PET) imaging ligands originally developed for neuroimaging may provide a means for imaging BCM as well. Previous studies have shown higher uptake of 11C-(+)-4-propyl-9-hydroxynaphthoxazine (PHNO), a dopamine D2/D3 agonist radioligand (D3-preferring), in the pancreatic tissue of healthy controls vs. T1DM in humans. In this study, we sought to determine whether 11C-PHNO, would be useful for measuring BCM. Eleven subjects (6 with T1DM, 4 males and 2 females, age 30.8 ± 11.4 years, BMI 24.4 ± 2.0, and 5 matched healthy controls, 3 males and 2 females, age 32.2 ± 11.4 years, BMI 26.4 ± 2.1) underwent abdominal PET/CT imaging using 11C-PHNO. Regions-of-interest (ROIs) were applied to the pancreas, liver, spleen, and kidney and time-activity curves (TACs) were produced and converted to standard uptake value (SUV) units. The distribution of activity between the head, body, and tail of the pancreas was also assessed. We observed that there was a 41% reduction in 11C-PHNO SUV in T1DM patients as compared to the healthy control group (p = 0.026). Moreover, there was a positive correlation between plasma c-peptide concentrations and 11C-PHNO SUV in the pancreas (r = 0.78), although this relationship did not reach statistical significance (p = 0.1), most likely due to the small sample size. These data suggest that dopamine D3 expression in pancreatic tissue might serve as a useful biomarker for assessing beta cell mass in diabetic humans. Disclosure E. Sanchez Rangel: None. J. Bini: None. N.B. Nabulsi: None. Y. Huang: None. K.C. Herold: None. R. Sherwin: Other Relationship; Self; QuintilesIMS, MannKind Corporation. Research Support; Self; Regeneron Pharmaceuticals, Inc.. Other Relationship; Self; ICON plc. R.E. Carson: Research Support; Self; Pfizer Inc., Bristol-Myers Squibb Company, Eli Lilly and Company, UCB, Inc., Siemens. G. Cline: None.