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Meeting ReportRadiopharmaceutical Chemistry: New Radiopharmaceuticals

18F-Fallypride PET to monitor pancreatic beta cell loss in diabetes mellitus

Adriana Garcia, Norah Milne, Mohammad Mirbolooki, Min-Liang Pan, Suresh Pandey, Cristian Constantinescu, Jonathan Lakey, Ping Wang, Jogeshwar Mukherjee and K George Chandy
Journal of Nuclear Medicine May 2009, 50 (supplement 2) 1947;
Adriana Garcia
1University of California, Irvine, Irvine, CA
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Norah Milne
1University of California, Irvine, Irvine, CA
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Mohammad Mirbolooki
1University of California, Irvine, Irvine, CA
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Min-Liang Pan
1University of California, Irvine, Irvine, CA
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Suresh Pandey
1University of California, Irvine, Irvine, CA
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Cristian Constantinescu
1University of California, Irvine, Irvine, CA
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Jonathan Lakey
1University of California, Irvine, Irvine, CA
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Ping Wang
1University of California, Irvine, Irvine, CA
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Jogeshwar Mukherjee
1University of California, Irvine, Irvine, CA
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K George Chandy
1University of California, Irvine, Irvine, CA
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Abstract

1947

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Objectives Our goal is to develop a non-invasive method to monitor β-cell loss in type 1 diabetes mellitus (T1DM). Dopamine D2 receptors (D2R) are present in rodent and human islets and co-localize with insulin granules. We report 18F-fallypride, a specific D2R ligand to image β-cells in a rat model.

Methods For in vitro studies, Sprague-Dawley rat pancreas were isolated for sections and islets isolated with collagenase (Sigma Type V) and dextran purification. 18F-fallypride binding was evaluated in the absence/presence of 100 μM haloperidol. After iv 18F-fallypride (0.8-1 mCi) normal rats and streptozotocin (STZ) pretreated rats were imaged in an Inveon scanner and subsequently studied ex-vivo. Radiochromatography (TLC) performed on homogenized pancreas and brain was compared to a standard 18F-fallypride.

Results 18F-fallypride binds to pancreas sections and isolated islet cells and is competed off by haloperidol, a D2R inhibitor, indicating specific binding. Depleting β-cells by treatment with STZ reduced 18F-fallypride binding by 70% and immunostain for insulin confirmed β-cell loss. Following iv 18F-fallypride administration, ex-vivo microPET imaging reveals 18F-fallypride in the pancreas. Brain had 0.15% and pancreas 0.05% injected dose (4 hrs pi) and TLC confirms the presence of 18F-fallypride in the pancreas. Co-administration of haloperidol or destruction of β-cells by STZ decreases pancreatic 18F-fallypride binding.

Conclusions Our results suggest that 18F-fallypride may be a suitable tracer for PET-based monitoring of β-cell-loss in T1DM and provide tools to measure responsiveness to new therapies and evaluate efficiency of islet graft survival.

  • © 2009 by Society of Nuclear Medicine
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Journal of Nuclear Medicine
Vol. 50, Issue supplement 2
May 2009
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18F-Fallypride PET to monitor pancreatic beta cell loss in diabetes mellitus
Adriana Garcia, Norah Milne, Mohammad Mirbolooki, Min-Liang Pan, Suresh Pandey, Cristian Constantinescu, Jonathan Lakey, Ping Wang, Jogeshwar Mukherjee, K George Chandy
Journal of Nuclear Medicine May 2009, 50 (supplement 2) 1947;

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18F-Fallypride PET to monitor pancreatic beta cell loss in diabetes mellitus
Adriana Garcia, Norah Milne, Mohammad Mirbolooki, Min-Liang Pan, Suresh Pandey, Cristian Constantinescu, Jonathan Lakey, Ping Wang, Jogeshwar Mukherjee, K George Chandy
Journal of Nuclear Medicine May 2009, 50 (supplement 2) 1947;
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