RT Journal Article
SR Electronic
T1 18F-Fallypride PET to monitor pancreatic beta cell loss in diabetes mellitus
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1947
OP 1947
VO 50
IS supplement 2
A1 Garcia, Adriana
A1 Milne, Norah
A1 Mirbolooki, Mohammad
A1 Pan, Min-Liang
A1 Pandey, Suresh
A1 Constantinescu, Cristian
A1 Lakey, Jonathan
A1 Wang, Ping
A1 Mukherjee, Jogeshwar
A1 Chandy, K George
YR 2009
UL http://jnm.snmjournals.org/content/50/supplement_2/1947.abstract
AB 1947 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.