Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two 99mTc complexes of (N-piperidinylethyl) hexamethyl diaminodithiol (NEP-DADT) have shown high brain uptake in rodents and lower primates. One of these 99mTc complexes has given positive images of the brain in man which are qualitatively related to regional brain blood flow (rCBF). In order to determine the structure of these 99mTc products, the corresponding 99Tc(NEP-DADT) complexes were prepared and characterized by HPLC, TLC, fast-atom-bombardment mass spectrometry (FAB MS) and other analytical techniques. These results indicate that the two 99Tc (NEP-DADT) complexes are syn and anti isomers (i.e. one isomer has the N-piperdinylethyl side chain located syn to the technetium oxo core while the other has this side chain located anti to the technetium oxo core).
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PMID:Brain imaging agents: synthesis and characterization of (N-piperidinylethyl) hexamethyl diaminodithiolate oxo technetium(V) complexes. 282 24

N-ethyl piperidinyl diaminodithiol (NEP-DADT), complexed with 99mTc has been developed as an agent for the measurement of brain blood flow using SPECT. Studies in patients have shown that 99mTc NEP-DADT enters rapidly into the brain, but also clears rapidly (t1/2 = 17 min). In this study nine new aminoalkyl DADT derivatives were synthesized, labeled with 99mTc and tested in mice with the aim of developing an agent with increased retention in the brain. In addition, relationships between chemical properties of the derivatives and their in vivo localization were investigated. The results were as follows: (a) the R-group and its isomeric configuration has a profound influence on the biodistribution; (b) 99mTc aminoalkyl DADT derivatives with apparent pKa values of greater than 6.9 show poor brain uptake (less than 0.40% dose at 5 min); (c) lengthening of the chain between the DADT moiety and the amino-R group from ethyl to hexyl generally increases the apparent pKa and consequently lowers brain uptake; (d) a correlation (r = 0.71) exists between initial brain uptake and the octanol-buffer partition coefficient; (e) 99mTc-4'-methyl NEP-DADT has the highest partition coefficient, relatively high uptake, and longest retention in the mouse brain. This complex has characteristics suited for brain blood flow measurements.
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PMID:Comparison of technetium-99m aminoalkyl diaminodithiol (DADT) analogs as potential brain blood flow imaging agents. 325 58

Several new lipophilic 99Tcm complexes have recently been described as alternatives to N-isopropyl (123I) iodoamphetamine (123IAMP) for measurement of regional cerebral blood flow (RCBF). In this study we have compared brain uptake and blood clearance of 99Tcm-N-ethylpiperidine-diamino dithiol (99Tcm-NEP DADT), its 4-methylated derivative (99Tcm-Me-NEP-DADT) and 99Tcm-hexamethyl-propylene-amine-oxime (99Tcm-HMPAO) with that of 123IAMP in two dogs. Single photon emission tomography (SPECT) was employed to measure brain accumulation and retention of the four radiopharmaceuticals. Cerebral uptake of the 99Tcm complexes (0.8-1.1%) was lower than that of 123IAMP (1.6% of the injected dose). There was considerable extracerebral activity in the dog's head, especially in the olfactory and snout regions. Because of slow blood clearance 99Tcm-HMPAO showed high uptake in these regions. Brain uptake of 99Tcm-HMPAO reached a plateau 5 to 10 min after intravenous injection and remained constant for the entire study period (1 h). 99Tcm-NEP-DADT, on the other hand, showed significant clearance from the brain after reaching maximal uptake at 10 to 15 min after injection. However, brain imaging with these agents was possible during the first 20 min. The mechanism of brain uptake, as well as the relationship between brain uptake and RCBF need to be evaluated for each of the four radiopharmaceuticals.
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PMID:Comparison of 99Tcm complexes (NEP-DADT, ME-NEP-DADT and HMPAO) with 123IAMP for brain SPECT imaging in dogs. 350 Oct 84