Radiolabelling optimisation of 7-bromo-5-[123I]-iodo-4-oxo-1,4-dihidroquinoline-2-carboxylic acid: a potential tracer for NMDA SPECT studies

The synthesis of 7-bromo-5-[¹²³I]-iodokynurenic acid is described. The tracer was prepared using a nucleophilic non-isotopic exchange reaction from the corresponding bromo derivative. Optimisation of the reaction parameters and HPLC purification were performed and the radiotracer was obtained in a chemical and radiochemical purity >95% and a specific activity of 235 Ci/mol.     

Preparation of radioiodinated L-α-methyl tyrosine, a tumour brain imaging agent

Preparation of radioidinated L-α-methyl tyrosine by the oxidative radioiodination using chloramine-T (CAT) and iodogen (1,3,4,6-tetrachloro,-3α, 6α-diphenyl glycoluril) to generate electrophilic radioiodine has been carried out. The factors affecting the labeling yield such as pH of the medium, reaction time, substrate and oxidizing agent concentrations have been investigated to optimize the conditions for the preparation of radioiodinated L-α-methyl tyrosine in high radiochemical yields. Side product impurities were observed at long reaction times and high oxidizing agent concentrations. Maximum radiochemical yields of 89.7±1.5% and 87.8±1.6% were obtained in case of CAT and iodogen, respectively. Separation and purification by high pressure liquid chromatography (HPLC) resulted in radiochemically pure products. Using high specific activity¹²³I, the SPECT brain imaging agent can be prepared.     

Synthesis and evaluation of 111In-labeled d-glucose as a potential SPECT imaging agent

The purpose of this study was to develop an efficient synthetic method for labeling d-Glucosamine with indium-111 (¹¹¹In), and to investigate the imaging properties of the resulting radiotracer in MDA-MB-468 xenograft models using single-photon emission computed tomography (SPECT). The precursor compound, 2-(4-Isothiocyanato benzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-deoxyglucosone (DOTA-DG), was synthesized from 2-d-Glucosamine. DOTA-DG was labeled with ¹¹¹In within 20 min. The labeling efficiency and radiochemical purity of ¹¹¹In-DOTA-DG were >95 and >96 % as determined by radio-HPLC. SPECT imaging studies were performed using nude mice bearing MDA-MB-468 mammary tumors after intravenous injection of at a dose of 1.11 MBq (0.1 mL) ¹¹¹In-DOTA-DG. Tumors were clearly delineated by SPECT imaging at 120 min after injection.     

Asymmetric synthesis of L-2-amino[3-11C]butyric acid, L-[3-11C]norvaline and L-[3-11C]valine

The short-lived radionuclide 11C (t1/2 = 20.4 min) has been used in the asymmetric synthesis of L-2-amino[3-11C]butyric acid, L-[3-11C]-norvaline and L-[3-11C]valine. The syntheses were performed by alkylation of [(+)-2-hydroxypinanyl-3-idene]-glycine tert-butyl ester under anhydrous conditions in tetrahydrofuran/1,3-dimethyl-3,4,5,6-tetrahydro-2-pyrimidinone with lithiated 2,2,6,6-tetramethylpiperidine as base, using the appropriate 11C-alkyl iodides prepared in a one-pot reactor from [11C]carbon dioxide. Following removal of the protecting groups, the -[3-11C]amino acids were obtained in 80-82% enantiomeric excess and in 9-25% radiochemical yields, decay corrected and calculated on the basis of the amount of [11C]carbon dioxide at the start of the syntheses within 50-55 min.     

Polycyclic azetidines. I. The preparation of benzo [c]-cis-6-azabicyclo[3.2.0] heptane

The title compound was prepared from compounds readily obtained from 2-carbomethoxy-I-indanone oxime ( 5 ) or from the N-chlorosulfonyl isocyanate adduct of indene ( 9 ). Apart from its ability to undergo transformation to the azetidine, compound 9 upon refluxing with excess LAII was found to undergo reductive decompostion to cis-2-hydroxymethyl-1-indanamine ( 2 ).     

First dinuclear Re/Tc complex as a potential bimodal Optical/SPECT molecular imaging agent

In this communication, a novel synthetic pathway has been applied to prepare a dual imaging agent in a single molecule. The dinuclear Re(I)/Tc(I) complex 6, namely [Re(CO)(3)(bipy){(4-PyrIDA)Tc(CO)(3)}], is the first example of a Re/Tc-based heterometallic assembly which could act as a potential bimodal Optical/SPECT probe. Interestingly, the Re(I) complex intermediate 4 exhibits significant photophysical properties for biological applications.     

The synthesis of 1-[2-(dimethylamino)ethyl]-7,12-dihydro-3H-[2]-benzoxepino[4,3-e]indole : A potential antidepressant agent

The structures of doxepin and serotonin were overlayed using molecular graphics and 1 - [2-(dimethylamino)ethyl] - 7, 12 - dihydro - 3H - [2] - benzoxepino[4,3-e]indole(1) was proposed as a potential antidepressant agent. This paper deals with the synthesis of the title compound. Key steps in the synthesis include a regioselective electrophilic substitution at C-4 of ethyl 5-hydroxy-1-indolecarboxylate (4) and subsequent modification to 7,12-dihydro-3H-[2]-benzoxepino[4,3-e]indole(12). Standard procedures were then used to construct the dimethylaminoethyl side chain to yeild the title compound (1).     

Imidazo [4,5-c] - and [4,5-6] pyridines

The synthesis of novel imidazo[4,5-c]pyridines 11-13 and imidazo[4,5-b]pyridines 18-20 is described using 2 as the starting material. The synthesis is generally applicable for the introduction of a wide variety of substituents.     

Experimental study on the collimator for increasing the resolution of N-isopropyl-p-(123I)iodoamphetamine (IMP) SPECT imaging of the brain

This study was carried out to design a new collimator for the present 123I-IMP SPECT imaging of the brain, which is hindered by the contamination of 124I and 126I. In this study we intended to increase spacial resolution along the transaxial direction and, at the same time, to compensate for the decrease of sensitivity by sacrificing the resolution along the axial direction to some extent. For this purpose, we developed 4 kinds of slat type units; ultrahigh resolution (UHR), high resolution (HR), high sensitivity (HS), and ultrahigh sensitivity (UHS). In practice, either UHR or HR is set to the detector together with either HS or UHS. After testing 4 kinds of combinations, we found that the combination of UHR-HS gave us far better images than those obtained with the conventional medium energy parallel hole collimator and was best suited for 123I-IMP SPECT imaging of the brain at present. We are now thinking of fusing these two units together into one collimator.     

Studies of polyazapentalenes. I. The preparation of 6-dehydroindazolo[1,2-a]benzotriazole

The photolysis of 1-(o-azidophenyl)-1H-indazole (IV) has been found to give a mix ture of 6-dehydroindazolo[1,2-a]benzolriazole (VI) and 2,2′-di(1-indazolyl)azobenzene (VII). On the other hand, 1-(o-nilrophenyl)-1H-indazole (1) was reduced with triethyl phosphite, affording VI and dibenzo[a,i] indazolo[1,2,′3-cd] indazolo[3,2,1-fg]-3,3a,5a,6,8a,8b-hexaaza-as-indacene (XIa).     

Synthetic and structural studies of [6]-, [7]- and [10]metacyclophanes

A new preparative sequence from 2,3-polymethylene-2-cyclopentenone 5 to 2,6-polymethylenebromobenzenes 3 (n = 6, 7, 10) and 2,6-polymethylenephenyllithiums 6 has been found. The reaction of 6 with various electrophiles produces a number of new compounds to disclose the unique reactivity of the aryl C-Li moiety surrounded by the polymethylene chain. Photolysis of 3a and 3b provides transannular products 8, 10 and 11, all arising from the proximity between the aromatic bromine and the aliphatic hydrogen intraannularly opposed to be removed as HBr. Spectrometric study gives quantitative data of the dependence of the molecular geometry upon the chain length and the aromatic substituents. The energy barriers ΔG_c^≠ of the conformational flipping are 17·4 kcal/mol (T_c 76·5°) for [6]metacyclophane (7a), 11·5 kcal/mol (T_c ?28°) for [7]metacyclophane (7b), ·8 kcal/mol for [10]metacyclophane (7c). The lower-energy process of the aliphatic chain in [6]metacyclophane derivatives is the pseudorotation with substituent-dependent barrier ΔG_c^≠ 11·1 kcal/mol (T_c ?31·5°) for 7a, 12·4 kcal/mol (T_c ?4·5°) for 3a and 12·7 kcal/mol (T_c 1·0°) for 12a. The rather large rotational barrier is attributed to the compressed structure of each system. The benzene ring distortion of the cyclophanes is deduced from the bathochromic shift of the B-band and the diamagnetic shift of the benzene proton signals in the PMR.     

Fundamental study for SPECT imaging with 123I produced by (p, 5n) reaction

The effects of higher-energy photon from 123I (p, 5n) on the SPECT image quality were evaluated. The quality was evaluated by image contrast and %rms. Image contrast had similar tendency to planar and SPECT FWHM value. %rms was affected by septal penetration. Using 140 keV high resolution collimator (140 keV HR), image contrast was superior to that for 300 keV medium energy collimator (300 keV ME), but septal penetration rate (SPR) was 18% and %rms was 10.5. When quantitation is required, the collimator with less SPR than 18% is recommended for SPECT imaging. Using 300 keV ME, SPR was 0.05%, but spatial resolution and image contrast were inferior to that for 140 keV HR.     

99mTc-DL-Homocysteine, a potential tumor imaging agent

The usefulness of 99mTc-labeled DL-homocysteine as a tumor imaging agent was further supported by high concentration distribution into the tumors of human lung or stomach tumor-bearing nude mice.