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Dynamic Positron Emission Tomography Imaging with 11C-ER176 to Delineate Macrophage Activation in Diabetic Gastroparesis
Summary Data Summary
Applicant Grover, Madhusudan
E-Mail Address grover.madhusudan@mayo.edu
Project Title Dynamic Positron Emission Tomography Imaging with 11C-ER176 to Delineate
Macrophage Activation in Diabetic Gastroparesis
CBU ID 20AU4118
External SubContract ID 32307-77
Diabetic Complication Gastro-Intestinal (GI)
Funding Program Group Pilot & Feasibility [PF2020]
Abstract Diabetic gastroparesis (DG) is a serious complication of diabetes mellitus which
results in significant morbidity. Patients suffer from chronic symptoms of
nausea, fullness, bloating and abdominal pain. These often result in
malnutrition as well as interfere with appropriate management of their diabetes
mellitus. Recent advancements driven by work in hyperglycemic animal models as
well as full thickness gastric biopsies from patients with DG have demonstrated
a macrophage-driven immune dysregulation as central to its pathogenesis.
Activated tissue macrophages, likely through paracrine mediators, induce injury
to the interstitial cells of Cajal, the gastric pacemaker cells which are also
involved in mechanotransduction. An enrichment of markers associated with
pro-inflammatory macrophages as well as loss of anti-inflammatory macrophages
has been demonstrated in gastroparesis. There are currently no non-invasive ways
of assessing immunopathology in the gastric muscle. Additionally, cellular
changes can be patchy and untargeted full-thickness biopsies do not allow a
comprehensive assessment of the gastric wall. Recently, there have been
advancements in radioligands that can be used to delineate activated
macrophages. A novel, third-generation translocator protein (TSPO)-specific
radioligand is 11C-ER176, which has shown high affinity and excellent in vivo
target-to-background binding. Our preliminary data shows that TSPO is expressed
in human gastric muscle macrophages. The overall goal of this proposal is to
determine the feasibility of 11C-ER176 dynamic PET/CT imaging for detecting
macrophage activation in vivo in gastric muscle of patients with DG. In this
pilot and feasibility study, we will examine a group of DG patients and matched
healthy volunteers with this imaging. Additionally, imaging findings will be
validated using tissue assessment of patients using cytometry by time of flight
(CyTOF). We anticipate that patients with DG will have enrichment of activated
macrophages, which will be detected by an uptake of 11C-ER176 on dynamic PET
imaging. This will be associated with enrichment of pro-inflammatory cellular
markers on assessment of gastric muscle tissue. Together, this study opens a new
paradigm for in vivo assessment of neuromuscular immunopathology in DG, which
typically requires invasive, deep tissue biopsy. A successful application of
this technique will open avenues for noninvasive assessment and guiding
treatment trials for diabetic gastroenteropathy as well as other inflammatory
gut disorders.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel Madhusudan Grover, MBBS
Ajit Goenka. MD
Salary Total Costs 37773
Supply Total Costs 3640
Equipment Total Costs 0
Travel/Other Total Costs 21480
Direct Costs 62893
Indirect Costs Proposed 0
Total Costs Proposed 62893
Total Costs Approved 100000
Start Date 11/1/2020
End Date 6/30/2023
IFO Name Grace, Janice
IFO E-Mail Address researchadmin@mayo.edu
IACUC/IRB No. 99999
IACUC/IRB Institution Mayo Clinic Rochester
Entity ID No.
Report Request Date 6/30/2023
T1D NO
TypeCount
Invoices 6
Progress Reports 2
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  20AU411832307-77Mayo Clinic Rochester7/31/2022$24,332.33$8,707.10$33,039.43$10,203.02View PDF
  View  20AU411832307-77Mayo Clinic Rochester7/31/2021$2,051.33$1,210.28$3,261.61$10,203.02View PDF
  View  20AU411832307-77Mayo Clinic Rochester2/28/2023$3,335.07$1,967.78$5,302.85$10,203.02View PDF
  View  20AU411832307-77Mayo Clinic Rochester11/30/2022$11,727.25$6,842.38$18,569.63$10,203.02View PDF
  View  20AU411832307-77Mayo Clinic Rochester10/31/2021$13,346.28$5,958.72$19,305.00$10,203.02View PDF
  View  20AU411832307-77Mayo Clinic Rochester1/31/2022$6,489.60$3,828.86$10,318.46$10,203.02View PDF
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