Pancreatic beta cell mass PET imaging and quantification with [11C]DTBZ and [18F]FP-(+)-DTBZ in rodent models of diabetes.
OBJECTIVE
The aim of this study is to compare the utility of two positron emission tomography (PET) imaging ligands ((+)-[(11)C]dihydrotetrabenazine ([(11)C]DTBZ) and the fluoropropyl analog ([(18)F]FP-(+)-DTBZ)) that target islet β-cell vesicular monoamine transporter type II to measure pancreatic β-cell mass (BCM).


METHODS
[(11)C]DTBZ or [(18)F]FP-(+)-DTBZ was injected, and serial PET images were acquired in rat models of diabetes (streptozotocin-treated and Zucker diabetic fatty) and β-cell compensation (Zucker fatty). Radiotracer standardized uptake values (SUV) were correlated to pancreas insulin content measured biochemically and histomorphometrically.


RESULTS
On a group level, a positive correlation of [(11)C]DTBZ pancreatic SUV with pancreas insulin content and BCM was observed. In the STZ diabetic model, both [(18)F]FP-(+)-DTBZ and [(11)C]DTBZ correlated positively with BCM, although only ∼25% of uptake could be attributed to β-cell uptake. [(18)F]FP-(+)-DTBZ displacement studies indicate that there is a substantial fraction of specific binding that is not to pancreatic islet β cells.


CONCLUSIONS
PET imaging with [(18)F]FP-(+)-DTBZ provides a noninvasive means to quantify insulin-positive BCM and may prove valuable as a diagnostic tool in assessing treatments to maintain or restore BCM.
Singhal
Tarun
T
Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA.
Ding
Yu-Shin
YS
Weinzimmer
David
D
Normandin
Marc D
MD
Labaree
David
D
Ropchan
Jim
J
Nabulsi
Nabeel
N
Lin
Shu-fei
SF
Skaddan
Marc B
MB
Soeller
Walter C
WC
Huang
Yiyun
Y
Carson
Richard E
RE
Treadway
Judith L
JL
Cline
Gary W
GW
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000000981:diagnostic imaging* / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D049268:Positron-Emission Tomography; D051381:Rats; D011924:Rats, Zucker; D013311:Streptozocin
D007328:Insulin; D013311:Streptozocin
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