Novel Cyclotron-Based Radiometal Production

Accomplishments: (1) Construction of prototype solution target for radiometal production; (2) Testing of prototype target for production of following isotopes: a. Zr-89. Investigation of Zr-89 production from Y-89 nitrate solution. i. Defined problems of gas evolution and salt precipitation. ii. Solved problem of precipitation by addition of nitric acid. iii. Solved gas evolution problem with addition of backpressure regulator and constant degassing of target during irradiations. iv. Investigated effects of Y-89 nitrate concentration and beam current. v. Published abstracts at SNM and ISRS meetings; (3) Design of 2nd generation radiometal solution target. a. Included reflux chamber and smaller target volume to conserve precious target materials. b. Included aluminum for prototype and tantalum for working model. c. Included greater varicosities for improved heat transfer; and, (4) Construction of 2nd generation radiometal solution target started

Imaging of cardiac neuronal function after cocaine exposure using Carbon-11 hydroxyephedrine and positron emission tomography

AbstractObjectives. The aim of the study was to define the effect of cocaine on the myocardial uptake and retention of C-11 hydroxyephedrine in the anesthetized dog model.Background. Cardiac toxcity of cocaine has been linked to its inhibitory effect on norepinephrine reuptake by the sympathetic nerve terminals of the heart. Carbon-11 hydroxyephedrine is a C-11-labled norepinephrine analog that has high specific affinity for uptake-1 and thus makes possible the assessment of the effect of cocaine on norepinephrine reuptake by cardiac sympathetic nerve terminals.Methods. The cardiac kinetics of C-11 hydroxyephedrine as assessed by dynamic positron emission tomographic imaging were used to characterize norepinephrine reuptake by the sympathetic nerve terminals. Carbon-11 hydroxyephedrine was injected intravenously before, as well as at 5 min and 2.5 h after, intravenous administration of 2 mg/kg body weight of cocaine in anesthetized dogs. Hemodynamic variables and microsphere-determined cardiac blood flow were also measured before and after cocaine exposure.Results. Intravenous injection of cocaine did not significantly affect hemodynamic variables and myocardial blood flow in the anesthetized animals. Compared with baseline, myocardial retention of C-11 hydroxyephedrine was significantly reduced by 78 ± 3% (mean ± SD) at 5 min and remained significantly reduced (28 ± 17%) at 2.5 h after cocaine injection. Cocaine administration after C-11 hydroxyephedrine injection (39 min) resulted in rapid biexponential clearance of C-11 hydroxyephedrine from myocardium.Conclusions. These results suggest prolonged effects of cocaine on the sympathetic nerve terminals of the heart. Positron emission tomography provides a noninvasive and sensitive means to objectively assess the cardiac pharmacokinetics of drugs such as cocaine

Cloning, function, and localization of human, canine, and Drosophila ZIP10 (SLC39A10), a Zn2+ transporter

Zinc (Zn2+) is the second most abundant trace element, but is considered a micronutrient, as it is a cofactor for many enzymes and transcription factors. Whereas Zn2+ deficiency can cause cognitive immune or metabolic dysfunction and infertility, excess Zn2+ is nephrotoxic. As for other ions and solutes, Zn2+ is moved into and out of cells by specific membrane transporters: ZnT, Zip, and NRAMP/DMT proteins. ZIP10 is reported to be localized at the apical membrane of renal proximal tubules in rats, where it is believed to play a role in Zn2+ import. Renal regulation of Zn2+ is of particular interest in light of growing evidence that Zn2+ may play a role in kidney stone formation. The objective of this study was to show that ZIP10 homologs transport Zn2+, as well as ZIP10, kidney localization across species. We cloned ZIP10 from dog, human, and Drosophila (CG10006), tested clones for Zn2+ uptake in Xenopus oocytes and localized the protein in renal structures. CG10006, rather than foi (fear-of-intimacy, CG6817) is the primary ZIP10 homolog found in Drosophila Malpighian tubules. The ZIP10 antibody recognizes recombinant dog, human, and Drosophila ZIP10 proteins. Immunohistochemistry reveals that ZIP10 in higher mammals is found not only in the proximal tubule, but also in the collecting duct system. These ZIP10 proteins show Zn2+ transport. Together, these studies reveal ZIP10 kidney localization, a role in renal Zn2+ transport, and indicates that CG10006 is a Drosophila homolog of ZIP10

Novel Cyclotron-Based Radiometal Production

Accomplishments: (1) Construction of prototype solution target for radiometal production; (2) Testing of prototype target for production of following isotopes: a. Zr-89. Investigation of Zr-89 production from Y-89 nitrate solution. i. Defined problems of gas evolution and salt precipitation. ii. Solved problem of precipitation by addition of nitric acid. iii. Solved gas evolution problem with addition of backpressure regulator and constant degassing of target during irradiations. iv. Investigated effects of Y-89 nitrate concentration and beam current. v. Published abstracts at SNM and ISRS meetings; (3) Design of 2nd generation radiometal solution target. a. Included reflux chamber and smaller target volume to conserve precious target materials. b. Included aluminum for prototype and tantalum for working model. c. Included greater varicosities for improved heat transfer; and, (4) Construction of 2nd generation radiometal solution target started

Evaluation of ( - )[18F]fluoroethoxybenzovesamicol as a new PET tracer of cholinergic neurons of the heart

18F-labeled ( - )fluoroethoxybenzovesamicol [( - )FEOBV] is a novel PET tracer which binds to the vesicular acetylcholine transporter of cholinergic neurons. To evaluate the in vivo binding specificity and kinetic properties of ( - )FEOBV, studies were performed in isolated working rat hearts. External [gamma],[gamma]-coincidence monitoring of hearts indicated high extraction of radiotracer by the myocardium and rapid wash-out of unbound tracer (>90% of maximal accumulation) within 5 min. Inclusion of ( - )vesamicol (10 [mu]M) throughout perfusion decreased the retention of ( - )FEOBV by 71% (P P in vivo studies with PET is likely to be limited by the low rate of specific binding in myocardium consistent with the low density of cholinergic neurons in the heart.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31806/1/0000752.pd