Objectives

A new radiotracer, ¹²⁴I-epidepride, has been developed for the imaging of dopamine D2/3 receptors (D2/3Rs). ¹²⁴I-Epidepride (half-life of ¹²⁴I=4.2 days) allows imaging over extended periods compared to (18)F-fallypride (half-life of ¹⁸F=0.076 days) and may maximize visualization of D2/3Rs in the brain and pancreas (allowing clearance from adjacent organs). D2/3 Rs are also present in pancreatic islets where they co-localize with insulin to produce granules and may serve as a surrogate marker for imaging diabetes.

Methods

¹²⁴I-Epidepride was synthesized using N-[[(2S)-1-ethylpyrrolidin-2-yl]methyl]-5-tributyltin-2,3-dimethoxybenzamide and ¹²⁴I-iodide under no carrier added condition. Rats were used for in vitro and in vivo imaging. Brain slices were incubated with (124)I-epidepride (0.75 μCi/cc) and nonspecific binding measured with 10 μM haloperidol. Autoradiograms were analyzed by OptiQuant. ¹²⁴I-Epidepride (0.2 to 0.3 mCi, iv) was administered to rats and brain uptake at 3 hours, 24 hours, and 48 hours post injection was evaluated.

Results

¹²⁴I-Epidepride was obtained with 50% radiochemical yield and high radiochemical purity (>95%). (124)I-Epidepride localized in the striatum with a striatum to cerebellum ratio of 10. Binding was displaced by dopamine and haloperidol. Brain slices demonstrated localization of ¹²⁴I-epidepride up until 48 hours in the striatum. However, the extent of binding was reduced significantly.

Conclusions

¹²⁴I-Epidepride is a new radiotracer suitable for extended imaging of dopamine D2/3 receptors and may have applications in imaging of receptors in the brain and monitoring pancreatic islet cell grafting.

OBJECTIVES: A new radiotracer, ¹²⁴I-epidepride, has been developed for the imaging of dopamine D2/3 receptors (D2/3Rs). ¹²⁴I-Epidepride (half-life of ¹²⁴I=4.2 days) allows imaging over extended periods compared to (18)F-fallypride (half-life of ¹⁸F=0.076 days) and may maximize visualization of D2/3Rs in the brain and pancreas (allowing clearance from adjacent organs). D2/3 Rs are also present in pancreatic islets where they co-localize with insulin to produce granules and may serve as a surrogate marker for imaging diabetes. METHODS: ¹²⁴I-Epidepride was synthesized using N-[[(2S)-1-ethylpyrrolidin-2-yl]methyl]-5-tributyltin-2,3-dimethoxybenzamide and ¹²⁴I-iodide under no carrier added condition. Rats were used for in vitro and in vivo imaging. Brain slices were incubated with (124)I-epidepride (0.75 μCi/cc) and nonspecific binding measured with 10 μM haloperidol. Autoradiograms were analyzed by OptiQuant. ¹²⁴I-Epidepride (0.2 to 0.3 mCi, iv) was administered to rats and brain uptake at 3 hours, 24 hours, and 48 hours post injection was evaluated. RESULTS: ¹²⁴I-Epidepride was obtained with 50% radiochemical yield and high radiochemical purity (>95%). (124)I-Epidepride localized in the striatum with a striatum to cerebellum ratio of 10. Binding was displaced by dopamine and haloperidol. Brain slices demonstrated localization of ¹²⁴I-epidepride up until 48 hours in the striatum. However, the extent of binding was reduced significantly. CONCLUSIONS: ¹²⁴I-Epidepride is a new radiotracer suitable for extended imaging of dopamine D2/3 receptors and may have applications in imaging of receptors in the brain and monitoring pancreatic islet cell grafting.

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.