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In a recent PET study we demonstrated the ability to measure amphetamine-induced DA release in the human cortex with the relatively high affinity dopamine D 2/3 radioligand [ 11 C]FLB 457 (Narendran et al., 2009). The aim of this study was to evaluate the reproducibility and reliability of [ 11 C]FLB 457 in the same imaging paradigm we used to measure amphetamine-induced DA transmission. Six healthy human subjects (3 males/3 females) were studied twice with [ 11 C]FLB 457, once at baseline and again three-hours following the end of the baseline scan. D 2/3 receptor binding parameters were estimated using a two-tissue compartment kinetic analysis in the cortical regions of interest and cerebellum (reference region). The test-retest variability and intraclass correlation coefficient were assessed for distribution volume (V T ), binding potential relative to plasma concentration (BP P ), and binding potential relative to non-displaceable uptake (BP ND ) of [ 11 C]FLB 457. The test-retest variability of [ 11 C]FLB 457 V T , BP P and BP ND were ≤ 15%, consistent with the published test-retest variability for this ligand in other brain regions (Vilkman et al., 2000;Sudo et al., 2001). In addition, no significant decrease in [ 11 C]FLB 457 BP ND was observed in the second scan compared to the first one. This suggests that the contribution of carryover mass of [ 11 C]FLB 457 to the measured reduction in [ 11 C]FLB 457 BP ND following amphetamine was relatively low. These data support the further validation of [ 11 C]FLB 457 as a tool to measure amphetamine-induced dopamine release in the human cortex.

In a recent PET study we demonstrated the ability to measure amphetamine-induced DA release in the human cortex with the dopamine D 2/3 radioligand [ 11 C]FLB 457. As previous studies in animals have shown that a relatively high fraction of the [ 11 C]FLB 457 signal in the cerebellum represents specific binding to D 2/3 receptors, there was concern that the use of the cerebellum as a measure of nonspecific binding (i.e., reference region) to derive [ 11 C]FLB 457 binding potential (BP ND ) would bias cortical dopamine release measurements. Thus, we evaluated the fractional contribution of specific binding to D 2/3 receptors in the human cerebellum for [ 11 C]FLB 457.Six healthy human subjects (5M/1F) were studied twice with [ 11 C]FLB 457, once at baseline and again following a single oral dose of 15 mg of aripiprazole, a D 2/3 partial agonist. [ 11 C]FLB 457 distribution volume (V T ) was estimated using kinetic analysis in the cortical regions of interest and potential reference regions. The change in [ 11 C]FLB 457 V T following aripiprazole ranged from −33 to −42% in the cortical regions of interest (ROIs). The aripiprazole-induced change in [ 11 C]FLB 457 V T in three potential reference regions suggests significant specific binding the cerebellum (CER, −17 ± 12%), but not pons (PON, −10 ± 10%) and centrum semiovale (CESVL, −3 ± 12%). Nevertheless, a re-analysis of the published [ 11 C]FLB 457 test-retest and amphetamine studies suggests that the use of the PON V T and CESVL V T as an estimate of nonspecific binding to derive [ 11 C]FLB 457 BP ND in dopamine release studies is unlikely to be successful because it leads to less reproducible outcome measures, which in turn diminishes the ability to measure dopamine release in the cortex. D 2/3 blocking studies with aripiprazole and [ 11 C]FLB 457 suggest specific binding to D 2/3 receptors in the cerebellum. These data also suggest that the contribution of specific binding to D 2/3 receptors in the cerebellum is lower than that in the cortical ROIs and that CER V T is mostly representative of nonspecific binding. Nevertheless, caution is advised when using reference tissue methods that rely solely on the cerebellum signal as an input function to quantify [ 11 C]FLB 457

Antibiotics have been widely used in the treatment of livestock diseases. However, the emergence of issues related to drug resistance prompted governments to enact a series of laws regulating the use of antibiotics in livestock. Following control of the problem of drug resistant bacteria, public attention has shifted to the recurring incidence of human health and safety issues caused by residual veterinary drugs in livestock products. To guarantee the safety and hygiene of meat, milk, and eggs from food-producing animals, governments and relevant agencies established laws and regulations for the use of veterinary drugs. It is, therefore, necessary to monitor the content of residual drugs in livestock products at regular intervals to assess whether the regulations have resulted in the effective management of food product safety, and to prevent and manage sudden problems related to this issue. A 2011-2015 livestock product post-marketing monitoring program launched by the Taiwan Food and Drug Administration (TFDA) inspected 1487 livestock products. Over the past 5 years, there were 34 samples identified that did not conform to the regulations; these samples included residue drugs such as β-agonists, chloramphenicols, β-lactam antibiotics, sulfa drugs, enrofloxacin, and lincomycin. Inspections of commercial livestock products with the consistent cooperation of agricultural authorities did not detect the drugs that were banned by the government, whereas the detection of other drugs decreased annually with an increase in the post-market monitoring sample size. In the future, the TFDA will continue to monitor the status of residual veterinary drugs in commercial livestock products, adjust the sampling of food products annually according to monitoring results, and closely cooperate with agricultural authorities on source management.