Evaluation of inhibitory effect of recreational drugs on dopaminergic terminal neuron by PET and whole-body autoradiography.

There is little investigation for the functional roles of peripheral dopamine. [(18)F]FDOPA has been used in cancer imaging (i.e., neuroendocrine and tumors pancreatic tumors) and neuroimaging (i.e., Parkinson's disease and Huntington's disease). Here, we accessed side effects of recreational drugs such as ketamine, cocaine, and methamphetamine on dopamine neurons in peripheral organs by using positron emission tomography (PET) imaging and quantitative whole-body autoradiography (QWBAR) with [(18)F]FDOPA. The images were applied for the measurement of specific binding ratios (SBRs) of striatum with the cerebellum as the reference region. Clear striatal [(18)F]FDOPA-derived radioactivity was observed. Moderate level of radiotracer accumulation was presented in the mucosal layers of the stomach and small intestine. The medulla layers of kidney had higher radioactivity than that of the cortex. Blocking images markedly eliminated the specific binding of [(18)F]FDOPA in the striatum and in peripheral organs such as stomachs, intestines, and kidney. Ketamine showed the highest inhibitory effect on striatal [(18)F]FDOPA-derived radioactivity followed by cocaine and methamphetamine. The current results demonstrated a useful crossing-validating tool that enhances the capability of [(18)F]FDOPA for further investigations of the alteration of dopaminergic neurons in the brain disorder or cancer diseases in peripheral tissues.

Imaging of regional metabolic activity by (18)F-FDG/PET in rats with transient cerebral ischemia.

Changes in regional metabolic activities induced by middle cerebral artery occlusion (MCAO) can influence patient outcome. Our aim was to demonstrate in a rat model that (18)F-FDG with positron emission tomography (PET) imaging is a quantitative, reproducible approach for identifying acute and sub-acute metabolic variations in infarct regions. We found that imaging with (18)F-FDG/PET enabled detection and quantification of ischemia-induced metabolic deficits and provided a sensitive and reliable means of assessing cerebral ischemic lesions compared with conventional neurological scoring systems in rodents.

Imaging the availability of serotonin transporter in rat brain with 123I-ADAM and small-animal SPECT.

BACKGROUND: Imaging serotonin transporters during antidepressant treatment in small animals is a useful tool for preclinical study during drug development. In this work, we aimed to demonstrate the feasibility of using 123I-ADAM and small-animal SPECT to monitor serotonin transporter availabilities in rat brains prior to and after administration of a selective serotonin re-uptake inhibitor. METHODS: Male Sprague-Dawley rats with and without administration of citalopram (4 mg x kg body weight) were examined in this study. During the process rat brains were scanned using a double-headed microSPECT system equipped with pinhole collimators. SPECT tomographic images and X-ray computed tomography (CT) were acquired after introducing 123I-ADAM via the tail vein. The 123I-ADAM specific binding was assessed by SPECT/CT fused image to draw regions of interest in the midbrain and cerebellum. Ex-vivo autoradiography was carried out as a parallel investigation to validate the SPECT technique. RESULTS: SPECT images displayed specific binding ratio in midbrain to be 0.91+/-0.30 averaged from three rats. Drug occupancies (95.47+/-1.56)% were shown after administration of citalopram in a dosage of 4 mg x kg. CONCLUSION: This study demonstrated that the serotonin transporter availability during antidepressant treatment in small animals can be assessed semi-quantitatively by using 123I-ADAM and SPECT.

Evaluation of F-18-labeled amino acid derivatives and [18F]FDG as PET probes in a brain tumor-bearing animal model.

UNLABELLED: 2-Deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG) has been extensively used as positron emission tomography (PET) tracer in clinical tumor imaging. This study compared the pharmacokinetics of two (18)F-labeled amino acid derivatives, O-2-[(18)F]fluoroethyl-l-tyrosine (l-[(18)F]FET) and 4-borono-2-[(18)F]fluoro-l-phenylalanine-fructose (l-[(18)F]FBPA-Fr), to that of [(18)F]FDG in an animal brain tumor model. METHODS: A self-modified automated PET tracer synthesizer was used to produce no-carrier-added (nca) l-[(18)F]FET. The cellular uptake, biodistribution, autoradiography and microPET imaging of l-[(18)F]FET, l-[(18)F]FBPA-Fr and [(18)F]FDG were performed with F98 glioma cell culture and F98 glioma-bearing Fischer344 rats. RESULTS: The radiochemical purity of l-[(18)F]FET was >98% and the radiochemical yield was 50% in average of 16 runs. The uptake of l-[(18)F]FET and l-[(18)F]FBPA-Fr in the F98 glioma cells increased rapidly for the first 5 min and reached a steady-state level after 10 min of incubation, whereas the cellular uptake of [(18)F]FDG kept increasing during the study period. The biodistribution of l-[(18)F]FET, l-[(18)F]FBPA-Fr and [(18)F]FDG in the brain tumors was 1.26+/-0.22, 0.86+/-0.08 and 2.77+/-0.44 %ID/g at 60 min postinjection, respectively, while the tumor-to-normal brain ratios of l-[(18)F]FET (3.15) and l-[(18)F]FBPA-Fr (3.44) were higher than that of [(18)F]FDG (1.44). Both microPET images and autoradiograms of l-[(18)F]FET and l-[(18)F]FBPA-Fr exhibited remarkable uptake with high contrast in the brain tumor, whereas [(18)F]FDG showed high uptake in the normal brain and gave blurred brain tumor images. CONCLUSION: Both l-[(18)F]FET and l-[(18)F]FBPA-Fr are superior to [(18)F]FDG for the brain tumor imaging as shown in this study with microPET.