Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02259 (NaI)
 1,823 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The benzodiazepine receptor tracer [123I]iomazenil (Ro 16-0154, IMZ) can be prepared in close to theoretical specific activity by the reaction of its tributyltin precursor (IMZ-SnBu3) with [123I]NaI in the presence of Iodogen. However, the labeling reaction is associated with variably high amounts of a volatile 123I byproduct. The purpose of these experiments was to characterize the volatile byproduct and to examine the effect on the course of the reaction of the following variables: solvent (MeOH, EtOH, HOAc, H2O), pH (2-7), oxidizing agent (chloramine-T, Iodogen, AcO2H), reaction temperature (22-128 degrees C) and structure of ArSnR3. The order of reactivity of oxidizing agents, at 22 degrees C for 30 min, was chloramine-T > Iodogen >> AcO2H. Raising the pH above 5.8 reduced the labeling, whereas raising the temperature increased the yield up to a maximum at 120 degrees (90%); at higher temperatures, decomposition occurred. The best conditions were 50 micrograms precursor, 50 microL 0.02 M chloramine-T; in aqueous HOAc (pH 3.3) at 120 degrees for 30 min. Variable amounts of volatile byproduct were observed for chloramine-T at different temperatures (2-21%) and for the three oxidizing agents at room temperature (3-22%). By contrast, the Bu3Sn derivatives of IBF, epidepride, beta-CIT and the Me3Sn derivative of beta-CIT gave high labeling yields with peracetic acid at room temperature, and < or = 2% volatile radioactivity. The volatile byproduct from the [123I]IMZ preparations was identified as I-[123I]iodobutane by its trapping characteristics and by its retention time in two different HPLC systems. Volatile activity was not generated in the absence of Bu3Sn precursor and was not due to the presence of impurities in the tributylstannyl precursor.
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PMID:Formation of 1-[123I]iodobutane in labeling [123I]iomazenil by iododestannylation: implications for the reaction mechanism. 828 59

The in vivo properties of a new radioiodinated probe of the dopamine and serotonin transporter, [123I]methyl 3 beta-(4-iodophenyl)tropane-2 beta-carboxylate ([123I]beta-CIT) were evaluated in baboons and vervet monkeys. The labeled product was prepared in 65.2 +/- 2.8% yield (mean +/- SEM; n = 18) by reaction of the tributylstannyl precursor with [123I]NaI in the presence of peracetic acid followed by high pressure liquid chromatography (HPLC) purification to give a product with radiochemical purity of 97.5 +/- 0.5% and specific activity of 500-1200 Ci/mmol. After intravenous administration, whole brain activity peaked at 6-10% injected dose within 1 h post injection (p.i.) and washed out in a biphasic manner with clearance half-lives of 1-2 and 7-35 h for the rapid and slow components, respectively. Excretion occurred primarily through the hepatobiliary route, with about 30% of the injected dose appearing in the GI tract after 5 h. Estimates of radiation absorbed dose gave 0.01, 0.1, 0.2 and 0.03 mGy/MBq to the brain, gall bladder wall, lower large intestine wall and urinary bladder wall, respectively. High resolution SPECT imaging in a baboon demonstrated high uptake of tracer in the region of the striatum (striatum:cerebellum ratio 4.0), in the hypothalamus (ratio 2.6) and in a midbrain region comprising raphe, substantia nigra and superior colliculus (ratio 2.0), with regional brain uptakes measured at 210 min p.i. of [123I]beta-CIT. The anatomical locations of the regions on the SPECT image were confirmed by coregistration with MRI. Plasma metabolites and pharmacokinetics were analyzed in baboons and vervets by ethyl acetate extraction and HPLC. The major metabolite was a polar, non-extractable fraction, which increased to > 50% of the plasma activity by 30-45 min p.i. A minor lipophilic (extractable) metabolite was also observed, increasing to about 4% at 2-3 h p.i. The plasma protein bound fraction, determined by ultrafiltration, was 74.8 +/- 1.4% (n = 6). The arterial input function was characterized by the sum of three exponential terms with half-lives of 0.3-1.7, 9.7-24.9 and 77-166 min, respectively, for the concentration of free parent compound. [123I]beta-CIT promises to be a useful marker for SPECT study of the monoamine uptake system in primate brain.
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PMID:Evaluation of the monoamine uptake site ligand [123I]methyl 3 beta-(4-iodophenyl)-tropane-2 beta-carboxylate ([123I]beta-CIT) in non-human primates: pharmacokinetics, biodistribution and SPECT brain imaging coregistered with MRI. 835 45

The novel cocaine analog RTI-121 [3 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid isopropyl ester] was evaluated as a probe for the in vitro labeling and localization of the dopamine transporter in the human brain. Saturation binding experiments conducted in sucrose-phosphate buffer (10 mM sodium phosphate, pH 7.4, 0.32 M sucrose) revealed high- and low-affinity binding components with affinity values (KD) of 0.25 +/- 0.04 and 4.9 +/- 1.6 nM (mean +/- SE) and densities (Bmax) of 56.8 +/- 13.8 and 147.7 +/- 23.4 pmol/g tissue, respectively. In contrast, when saturation binding experiments were performed in phosphate-buffered saline (10 mM Na2HPO4, 1.8 mM KH2PO4, 136 mM NaCl, 2.8 mM KCl, 10 mM NaI, pH 7.4), a 9-fold decrease in the density of the low-affinity component was noted, suggesting that the low-affinity RTI-121 binding site is associated with the region of the transporter involved in the ionic dependence of substrate recognition and/or uptake. The rank order of potency for inhibition of [125I]RTI-121 binding to human caudate membranes demonstrates that the radioligand selectively labels the dopamine transporter (GBR 12909 > RTI-121 > mazindol > nomifensine > (-) cocaine > desipramine > citalopram). Autoradiographic mapping of [125I]RTI-121 revealed very high densities of cocaine recognition sites over areas known to be rich in dopaminergic innervation, including the caudate, putamen, and nucleus accumbens. Moderate densities were also observed over the substantia nigra and the ventral tegmental area. Low-to-background labeling of [125]RTI-121 was seen throughout the cerebral cortex, amygdaloid nuclei, globus pallidus, and thalamus. In comparison with the autoradiographic distribution of the cocaine analogs [3H]WIN 35,428 (or CFT) and [125I]RTI-55 (or beta-CIT), the labeling pattern for [125I]RTI-121 was more restricted. These studies demonstrate that [125I]RTI-121 labels dopamine-rich brain regions with greater selectivity than other currently available cocaine analogs, which makes it a potentially superior imaging probe for mapping the dopamine transporter in the human brain.
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PMID:Mapping dopamine transporters in the human brain with novel selective cocaine analog [125I]RTI-121. 886 67