BACKGROUND: A noninvasive method of monitoring the loss of islet cells can provide an earlier and improved diagnosis for therapeutics development of preclinical phases of diabetes. The use of [(18)F]fallypride, a dopamine D2/D3 receptor radiotracer, has been developed as a surrogate marker to evaluate loss of pancreatic islet cells in a rodent model of type 1 diabetes. MATERIALS AND METHODS: Healthy Sprague-Dawley rats were administered [(18)F]fallypride and imaged for 2 h in a positron emission tomography (PET)/computed tomography (CT) scan. Diabetes was then induced in the same rats by administration of streptozotocin, and a PET/CT scan was performed 4 days after establishing diabetes. Pancreata of a separate set of rats were evaluated by insulin immunostaining for loss of islet cells by streptozotocin. RESULTS: Blood glucose levels of 125 mg/dL and 550 mg/dL were established for those rats without and with diabetes, respectively. [(18)F]Fallypride uptake in the pancreas of both groups of rats was rapid, but the rats with diabetes showed a significantly lower uptake (less than 50%). The specific binding ratio was decreased by 77% in the diabetic rats. CONCLUSIONS: [(18)F]Fallypride can be a useful surrogate marker for monitoring changes in pancreatic islet cells, thus providing a noninvasive method to evaluate efficacy of therapeutics.
BACKGROUND: A noninvasive method of monitoring the loss of islet cells can provide an earlier and improved diagnosis for therapeutics development of preclinical phases of diabetes. The use of [(18)F]fallypride, a dopamine D2/D3 receptor radiotracer, has been developed as a surrogate marker to evaluate loss of pancreatic islet cells in a rodent model of type 1 diabetes. MATERIALS AND METHODS: Healthy Sprague-Dawley rats were administered [(18)F]fallypride and imaged for 2 h in a positron emission tomography (PET)/computed tomography (CT) scan. Diabetes was then induced in the same rats by administration of streptozotocin, and a PET/CT scan was performed 4 days after establishing diabetes. Pancreata of a separate set of rats were evaluated by insulin immunostaining for loss of islet cells by streptozotocin. RESULTS:Blood glucose levels of 125 mg/dL and 550 mg/dL were established for those rats without and with diabetes, respectively. [(18)F]Fallypride uptake in the pancreas of both groups of rats was rapid, but the rats with diabetes showed a significantly lower uptake (less than 50%). The specific binding ratio was decreased by 77% in the diabeticrats. CONCLUSIONS:[(18)F]Fallypride can be a useful surrogate marker for monitoring changes in pancreatic islet cells, thus providing a noninvasive method to evaluate efficacy of therapeutics.
Authors: Tarun Singhal; Yu-Shin Ding; David Weinzimmer; Marc D Normandin; David Labaree; Jim Ropchan; Nabeel Nabulsi; Shu-fei Lin; Marc B Skaddan; Walter C Soeller; Yiyun Huang; Richard E Carson; Judith L Treadway; Gary W Cline Journal: Mol Imaging Biol Date: 2010-09-08 Impact factor: 3.488
Authors: Robin Goland; Matthew Freeby; Ramin Parsey; Yoshifumi Saisho; Dileep Kumar; Norman Simpson; Joy Hirsch; Martin Prince; Antonella Maffei; J John Mann; Peter C Butler; Ronald Van Heertum; Rudolph L Leibel; Masanori Ichise; Paul E Harris Journal: J Nucl Med Date: 2009-02-17 Impact factor: 10.057
Authors: Fabiola Souza; Norman Simpson; Anthony Raffo; Chitra Saxena; Antonella Maffei; Mark Hardy; Michael Kilbourn; Robin Goland; Rudolph Leibel; J John Mann; Ronald Van Heertum; Paul E Harris Journal: J Clin Invest Date: 2006-05-18 Impact factor: 14.808
Authors: Jason Bini; Mika Naganawa; Nabeel Nabulsi; Yiyun Huang; Jim Ropchan; Keunpoong Lim; Soheila Najafzadeh; Kevan C Herold; Gary W Cline; Richard E Carson Journal: J Nucl Med Date: 2018-01-25 Impact factor: 10.057
Authors: Judith Korner; Gary W Cline; Mark Slifstein; Pasquale Barba; Gina R Rayat; Gerardo Febres; Rudolph L Leibel; Antonella Maffei; Paul E Harris Journal: Mol Metab Date: 2019-02-27 Impact factor: 7.422