Technetium-99m nitride radiopharmaceuticals

Following the introduction of an efficient method for the preparation of technetium-99m complexes containing a terminal Tc-N multiple bond, under conditions suitable for nuclear medicine applications, new radiopharmaceuticals for heart and brain imaging have been discovered. These compounds belong to the class of bi-substituted, square-pyramidal nitride TcV complexes with dithiocarbamate ligands, and are the first examples of radiopharmaceuticals of this type exhibiting interesting biological properties. The peculiar chemical characteristics of the Tc-N core can also be conveniently utilized for the design of radiopharmaceuticals incorporating bioactive peptides and having definite structural features.     

99mTc放射性药物化学

^99mTc放射性药物在科学研究和临床上已经得到了广泛的应用,但如何发展药效更好的药物以适应临床诊断的需求,依然是亟待解决的问题。新药物配体和金属核的引入以及新的标记方法的发展是目前^99mTc的放射性药物的热点。本文介绍^99mTc放射性药物化学的几种新标记方法,包括羰基锝标记的新型配体和新方法、^99mTc高价配合物的制备和应用等,旨在对有关研究者提供参考。     

Characteristics and behavior of a99Mo/99mTc generator using irradiated titanium molybdate as column matrix

A⁹⁹Mo/^99mTc generator, system was made with a performed titanium molybdate gel. The irradiation was carried out at a medium neutron flux of 1.5×10¹³ n cm^–2·s^–1. The irradiated matrix was loaded on top of a column composed of hydrous zirconium oxide alumina. The elution efficiency and the amount of total technetium per mCi^99mTc in the generator eluents have been determined. Molybdenum breakthrough has also been determined and compared with literature values. The influence of the particle size, water content, neutron flux and molybdenum content on the total^99mTc-activity has been investigated.     

Technetium-99m extraction and transport across tri-n-octylamine-xylene based supported liquid membranes

The nuclear properties of^99mTc radionuclide are ideal for organ imaging. Study of the technetium transport across supported liquid membranes has been performed to get data for its separation from other elements. Tri-n-octylamine diluted in xylene was used to constitute the liquid membranes, supported in polypropylene microporous films. Stripping on the product solution side was performed with dilute NaOH solutions. The effect of sulphuric acid, nitric acid and hydrochloric acid in the feed on transport of^99mTc as TcO ₄ ^– ions has been studied. The permeability of the given ions determined from kinetic activity data has been found to be in the order of PH₂SO₄>PHCl>PHNO₃. The flux values have been calculated based on this permeability data. The increase in carrier concentration has shown an increase in flux and permeability values to a given optimum concentration. The increase in temperature has been found to reduce the transport of Tc ions. The optimum conditions for transport of^99mTc for the given acid concentration have been determined. Mechanism of Tc ion transport has also been provided based on chemical reactions involved at the membrane interfaces and uptake of Tc ions by the membrane. MoO ₄ ^2– ions do not permeate through membrane under optimum conditions of transport for TcO ₄ ^2– ions from H₂SO₄ solution.     

Preparation and performance studies of 99Mo/99mTc column generators based on nano zirconium molybdate

Journal of Radioanalytical and Nuclear Chemistry - Highly-porous nano zirconium molybdate-99Mo (Zr99Mo) gels were precipitated by a simple new radiochemical process from mixtures of...     

Technetium-99m dextran kit: formulation and biological behaviour

A new formulation of stannous-dextran (Sn-Dx) freeze dried kit, containing 60 mg dextran (Dx-70) and 0.08 mg SnCl₂·2H₂O, to be labelled with^99mTc, has been developed. At pH 6.5–7.0. the labelling efficiency was greater than 95%. Gel chromatography column scanning technique was applied for radiochemical purity determination of^99mTc-Dx preparation and the degree of in vivo plasma protein binding. Not less than 70% of the administered activity was bound to plasma and remained constant over a 1h period. The biological behaviour after intravenous injection of^99mTc-Dx kit was characterized by high and efficient yield of the radiopharmaceutical. The preliminarly clinical results on normal subjects showed that the radiopharmaceutical could be a useful agent for scintigraphy of leg lymph vesel, pelvic and inguinal lymph nodes. The activity uptake in liver and kidney (60 min) was relatively very low, whereas the urinal bladder activity (30 min) represents the drainage of the activity entering the blood stream after interdigital injection of^99mTc-Dx.     

Technetium-99m complexes with steroid-2-aminooxyethyliminodiacetic acid conjugates

Conjugates of 2-aminooxyethyliminodiacetic acid with estrone, testosterone, epiandrosterone, 17-alpha-hydroxy-progesterone and progesterone were synthesized and their complexes with Tc-99m were successfully prepared in good yields, which indicated the agent to be promising for metal-labeling of biomolecules and related substances containing one or more carbonyl groups. The biodistribution and scintigraphic studies in mice bearing Ehrlich tumor and mammary tumor showed that the radioactivity accumulated considerably in the tumor tissues, but the tumor images were somewhat obscured.     

Organic Synthesis and Technetium-99m Labeling of Some Amino-Phenol Ligands

We reported the synthesis and labeling of one tetradentate and two pentadentate amino-phenol ligands with technetium-99m by the direct pertechnetate addition and by ligand exchange methods. Labeling by direct pertechnetate addition was attended by adding pertechnetate eluate to the ethanolic solution of the amino-phenol ligands at pH 9. Stannous chloride dihydrate was used as reducing agent. Exchange studies were carried out via the use of the following ^99mTc-chelates: ^99mTc-DTPA, ^99mTc-gluconate, ^99mTc-tartrate and ^99mTc-citrate complexes. Ligand exchange method was achieved by incubation the ligand solutions with ^99mTc-co-ligands complexes in 0.05M bicarbonate buffer pH 9. At this pH value the ^99mTc-co-ligands dissociated and the more stable new ^99mTc-ligands were formed with high radiochemical yield 95%. The radiochemical yield of ^99mTc-labeled amino-phenol ligands were estimated by solvent extraction, electrophoresis and HPLC methods. The produced technetium-99m amino-phenol complexes were neutral, lipophilic and stable during the period of 24 hours.     

Preliminary study of quality control of99m Tc from99Mo generators

The separation of Tc(VII) from Mo(VI) by thin-layer and paper-chromatography is discussed. Some aspects concerning the formation and identification of lower oxidation states of Tc(VII) are also mentioned. Finally, a spot test is recommended for the determination of Mo(VI) and Al, which can be contaminants in the Tc(VII) solution eluted from the⁹⁹Mo column, filled with Al₂O₃.     

Isotope exchange between 12-molybdocerate(IV) and sodium molybdate-99Mo in aqueous media

12-molybdocerate(IV) gel labelled with⁹⁹Mo has been prepared via isotope exchange between a column of inactive molybdate matrix and a mobile solution of⁹⁹-Mo-sodium molybdate(VI) in 0.1 mol·dm^–3 HNO₃. The composition and nature of the reaction mixture, concentration of Mo(VI) in the reactants, reaction temperature and/or drying temperature of the gel matrix on the exchange yeild of⁹⁹Mo and time of reaction are explored using the batch equilibration and/or the chromatographic column methods. The obtained material is evaluated for use in preparation of elution-type⁹⁹Mo-^99mTc generators.     

Zur Analyse von Technetium-99m und Ruthenium-103, 106 in Spaltprodukten

Ohne Zusammenfassung     

Technetium-99m Radiopharmaceuticals for Ideal Myocardial Perfusion Imaging: Lost and Found Opportunities

The favorable nuclear properties in combination with the rich coordination chemistry make technetium-99m the radioisotope of choice for the development of myocardial perfusion tracers. In the early 1980s, [^99mTc]Tc-Sestamibi, [^99mTc]Tc-Tetrofosmin, and [^99mTc]Tc-Teboroxime were approved as commercial radiopharmaceuticals for myocardial perfusion imaging in nuclear cardiology. Despite its peculiar properties, the clinical use of [^99mTc]Tc-Teboroxime was quickly abandoned due to its rapid myocardial washout. Despite their widespread clinical applications, both [^99mTc]Tc-Sestamibi and [^99mTc]Tc-Tetrofosmin do not meet the requirements of an ideal perfusion imaging agent due to their relatively low first-pass extraction fraction and high liver absorption. An ideal radiotracer for myocardial perfusion imaging should have a high myocardial uptake; a high and stable target-to-background ratio with low uptake in the lungs, liver, stomach during the image acquisition period; a high first-pass myocardial extraction fraction and very rapid blood clearance; and a linear relationship between radiotracer myocardial uptake and coronary blood flow. Although it is difficult to reconcile all these properties in a single tracer, scientific research in the field has always channeled its efforts in the development of molecules that are able to meet the characteristics of ideality as much as possible. This short review summarizes the developments in ^99mTc myocardial perfusion tracers, which are able to fulfill hitherto unmet medical needs and serve a large population of patients with heart disease, and underlines their strengths and weaknesses, the lost and found opportunities thanks to the developments of the new ultrafast SPECT technologies.     

The study of conditions for the preparation and application of99Mo−99mTc generators starting from irradiated molybdenum metal

⁹⁹Mo−^99mTc generators were prepared starting from irradiated molybdenum metal instead of MoO₃ in order to use reactor irradiation space more economically. The adsorption of molybdenum as sodium molybdate on different kinds of alumina was investigated. The effect of the pH of the column and the aqueous phase concentration of molybdenum were studied and related to the elution yield of^99mTc. A study of the radiation damage effect indicated that generators having a high elution efficiency of 90% could be prepared in the 100–600 mCi range. The losses of⁹⁹Mo were minimized to 10⁻⁵-10⁻⁴% and those of alumina to 2–5 μg/ml eluate.     

99mTc标记COI配合物的制备及其用作心室显像剂的初步研究

通过改变异腈配体的结构和配合物的中心核,以期获得标记方法简单、放化纯度高以及生物性能优良的新型心室显像剂.以环辛胺为原料,通过甲酰胺化和脱水两步反应制得配体环辛基异腈(COI),并以氯化亚锡为还原剂和二硫代肼基甲酸甲酯为供氮体,通过配体交换反应得到放化纯度大于95%的^99mTcN-COI标记物.以氯化亚锡为还原剂直接标记制得放化纯度大于95%的^99mTc-COI配合物.两种标记物在室温下放置6h以上,其放化纯度无明显变化.在正常昆明小鼠体内进行的生物分布实验研究结果显示,^99mTcN-COI和^99mTc-COI在心脑中有一定摄取,但肝、肺及血等本底摄取相对较高.二者在血液中都有很高的浓集,且滞留也很好,其中^99mTc-COI配合物在静脉注射后60min时的血/心、血/肝和血/肺摄取比分别为6.67,1.54和2.07,有望成为一种新型的制备方法简单的心室显像剂.     

Technetium-99m labeling of hippuric and p-amino-hippuric acid in the presence of DTPA: Biological and pharmacokinetic evaluation and comparison with99mTc-DTPA

^99mTc-Hipp as a modified^99mTc-DTPA, and^99mTc-PAH as a new renal agent are developed. Each veal of lyophilised kit contain hippuric (Hipp) or p-aminohippuric acid (PAH), diethyltriaminepentaacetic acid as calciumtrisodium salt (CaNa₃DTPA) and stannouschloride (SnCl₂·xH₂O), in molar ratio Hipp/PAH:DTPA=4∶1. They are high radiochemical purity radiopharmaceuticals, with hydrophilic character and low percentage of protein binding. The ITL chromatography and HPLC analyses of these labeled compounds have shown almost identical results as^99mTc-DTPA, but their biological behavior in rats confirm certain differences.^99mTc-Hipp is a renal agent clearing by the glomerular system, with better pharmacokinetical parameters than^99mTc-DTPA:t _1/2(α)=4.1 min,t _1/2(β)=198.6 min,K _cl=1.2·10⁻²min⁻¹ and a twofold value for blood clearance (Cl=2.07 ml/min).^99mTc-PAH is a quite different renal agent, rapidly secreted by kidney as a tubular secretion agent. Its pharmacokinetical parameters:t _1/2(α)=2.5 min,t _1/2(β)=41.7 min andK _cl=5.1·10⁻⁴ min⁻¹ are almost equal to those of^99mTc-MAG₃, but the blood clearance of Cl=5.22 ml/min is even higher than that of IOH clearance.     

<Superscript>99</Superscript>Mo/<Superscript>99m</Superscript>Tc generators based on aluminum molybdate gel matrix prepared by nano method

A procedure for preparation of ⁹⁹Mo/^99mTc radioisotope generator based on low specific activity neutron activated ⁹⁹Mo was developed. Aluminum molybdate(VI)-⁹⁹Mo of high Mo(VI) content (~?364 mg/g Al⁹⁹Mo) was prepared by mixing low specific activity molybdate(VI)-⁹⁹Mo and aluminum mixture solution with isoamyl alcohol. Al⁹⁹Mo gel matrix was precipitated when the pH of the mixture solution was raised to ~?5 by addition of NaOH to the mixture. Radiometric measurements indicate the strong fixation of Molybdate(VI)-⁹⁹Mo species in the form of the sparingly insoluble Al⁹⁹Mo gel matrix. The prepared AlMo gel matrix was physiochemically characterized. Al⁹⁹Mo gel matrix was used as a base material for preparation of ⁹⁹Mo/^99mTc generator. The ^99mTc eluted from ⁹⁹Mo/^99mTc radioisotope generator was found to have relatively high elution yield (84?±?2.3%), radionuclidic (≥?99.99%), radiochemical (98.1?±?0.9%) and chemical purity.     

The effect of pressure on neutron irradiated ammonium chromates

The effect of pressure on neutron irradiated ammonium chromate and ammonium dichromate has been studied. Compression was found to have no effect on the retention and on the M and DP yields in both salts. Pressure applied before heating was found to retard annealing in ammonium chromate, while it appeared to have no influence on the annealing of ammonium dichromate.