[en] The electronic structures of ⁹⁹Tc^m-complexes are calculated by SCC-DV-Xa method, and the retention mechanism is discussed. The results indicate the retention of ⁹⁹Tc^m-complexes in the brain is dependent on their LUMO energy levels and instability. The higher their LUMO energy levels are, the better their retention in the brain is. And the weakening of the bond between Tc and the nitrogen atom of dioxime causes them more unstable, this might also lead to the better retention in the brain

[en] Optimized geometries of nine ⁹⁹Tc^m-Q complexes are obtained using simulated annealing method and Monte Carlo method of molecular dynamics. Then the structures of these complexes are optimized by molecular mechanics, and further optimized by semi-empirical quantum mechanics method--ZINDO/1 and the electronic structures are calculated. The result revealers that there is a curve correlation between the heart uptake and the dipole moment and the acme of the curve may be inferable in the range from 7 to 9, and that heart uptake has some relationship with E_LUMO

[en] Introduction: The most abundant subtype of cerebral nicotinic acetylcholine receptors (nAChR), α4β2, plays a critical role in various brain functions and pathological states. Due to rapid technological progress in chemistry, bioinformatics, structural biology and computer technology, computer aided drug design (CADD) plays a more and more important role in today's drug discovery. Methods: Two novel 3-pyridyl ether nicotinic ligands-3-((pyridine-2-yl)methoxy)-5-iodopyridine, and 3-(((S)-pyrrolidin-2-yl)methoxy)-5-((4-iodobenzyloxy)-methyl)pyridine were designed and synthesized and radiolabeled with I-125 based on our 3D-QSAR models reported previously. Their ability to label high-affinity brain nicotinic acetylcholine receptors (nAChRs) was evaluated. Results: [¹²⁵I]3-((pyridin-2-yl)methoxy)-5-iodopyridine shows rapid accumulation and elimination with peak (1.86%ID/g) at 5 min post injection, but has high blood uptake. [¹²⁵I]3-(((S)-pyrrolidin-2-yl)methoxy)-5-((4-iodobenzyloxy)methyl)pyridine entered the brain with maximal uptake value 3.01%ID/g at 15 min after injection, and showed approximately 27% inhibition of radioactivity uptake in thalamus in mice pretreated with nicotine. Conclusions: The results of this preliminary study show that [¹²⁵I]3-(((S)-pyrrolidin-2-yl)methoxy)-5-((4-iodobenzyloxy)methyl)pyridine shows relatively high uptake to the brain, however, since the in vivo selectivity for α4β2 nAChRs was not enough, [¹²⁵I]3-(((S)-pyrrolidin-2-yl)methoxy)-5-((4-iodobenzyloxy)methyl)pyridine does not have the required properties for imaging nAChRs using SPECT. Structure optimization is needed for specific visualization of brain α4β2 nAChRs in vivo.

[en] Twelve new peptide or pseudo-peptide chelators have been synthesized in the course of our continuing investigation of ^99mTc-labelled peptides for application for renal imaging agents. All compounds were characterized on the basis of, IR, ¹HNMR, ¹³CNMR spectroscopy, as well as MS and elemental analysis. All peptides yield stable ^99mTc complexes using Sn(II) reactive coupling and exhibit renal uptake. Linear regression analysis between Logarithm of renal uptake value (RU) and the parameters obtained by the ZINDO/1 method was performed. Some equations were obtained which showed that molecular polar and charge have some relationship with their renal uptake

[en] The geometries of [⁹⁹Tc^m-Mine]⁺ complexes are optimized by the semi-empirical quantum mechanics method--ZINDO/1 and many physical and chemical descriptors are obtained. Step multiple regression between these descriptors and heart initial uptake is done and an equation is obtained. New uptake mechanism is proposed: the complexes with low polarity might be passively transported into the myocardium cell, and would be 'trapped' by proteins with negative charge on the membrane mitochondria because of the Q_max⁺ of the complexes

[en] Optimized geometries of twelve ⁹⁹Tc^m-N₃S pseudo-peptide complexes, which have been synthesized and labelled with ⁹⁹Tc^m for further biodistribution study, are obtained by molecular mechanics methods. These complexes are optimized by semiempirical quantum mechanics method--ZINDO/1 and the electronic structures are calculated. Quantitative structure-activity relationships (QSAR) are investigated by multiple linear regression analysis method. Several equations are obtained which reveal that molecular dipole moment (μ) and charge of the complexes are all significant descriptors correlating to renal uptake, and volume of the complexes correlates well with liver uptake

[en] Based on crystal data of ⁹⁹Tc^m-d,l-HMPAO, the structures of ⁹⁹Tc^m-d,l-PAO complexes (⁹⁹Tc^m-d,l-HMPAO, ⁹⁹Tc^m-d,l-CBPAO, ⁹⁹Tc^m-d,l-OCBPAO, ⁹⁹Tc^m-d,l-EOCBPAO, ⁹⁹Tc^m-d,l-IPOCBPAO) are optimized. The total energy of molecule, dipole moment of molecule, net charge of atom and the molecular orbital energy of HOMO and LUMO are calculated. The results indicate that brain retention ability of ⁹⁹Tc^m-d,l-PAO complexes depends on the in vitro instability of the complexes, which are consistent with the results of experiment. The influence of molecular polarity and intermolecular hydrogen bond on molecular lipophilicity of complexes are investigated. The conclusion provides the theoretical basis for studying reasonable drug design and brain retention mechanism

[en] [^99mTc(CO)₃-EC] was prepared and its biodistribution in mice was studied. Biodistribution study revealed that it had pretty high initial kidney uptake and fast renal clearance. It would be helpful for further study of carbonyl technetium core used in the field of kidney imaging agents. (authors)

[en] To explore the synthetic methods of phosphine mixed complexes of technetium-99m and look for new heart imaging agents, one N₃S ligand (MVNE) and three phosphine ligands were synthesized. ⁹⁹Tc^m-MVNE prepared at room temperature through ligand-exchange reaction reacts with the three phosphine ligands respectively to obtain three mixed complexes of ⁹⁹Tc^m-MVNE-phosphine. The biodistribution studies in mice indicate that these complexes exhibit pretty high myocardial uptake and high blood clearance rate

[en] In order to develop new phosphine schiff base mixed complexes of ⁹⁹Tc^m used for myocardial imaging, an N₃S ligand (MVNE) and four phosphine ligands are synthesized. ⁹⁹Tc^m-MVNE, which is prepared under room temperature through ligand-exchange reaction, reacts with the four phosphine ligands respectively to obtain mixed complexes of ⁹⁹Tc^m-MVNE-phosphine. Biodistribution of the four complexes in mice indicates that uptake is demonstrated in heart, the activity is cleared rapidly from blood and the clearance half-time is less than 10 min. However, the retention ability of the four complexes in heart is not ideal and heart/background ratios is low. The distribution results in mice indicate these complexes exhibit certain myocardial uptake