The interactions of99mTc phosphorus radiopharmaceuticals and human serum proteins

Dialysis and precipitation methods have been used to study the binding affinity of selected technetium-99m phosphorus radiopharmaceuticals to human serum proteins. The binding affinities of three different^99mTc bone imaging agents were found to be inversely related to their respective clearance rates from blood in vivo. The binding order showed^99mTcPPi>^99mTcHEDP>^99mTcMDP. The^99mTc phosphorus radiopharmaceuticals were bound primarily to alpha globulins. The results suggest that the binding of^99mTc phosphorus radiopharmaceuticals to human serum proteins in blood is largely determined by their affinities to the alpha globulins.     

Effect of experimental conditions on the in vitro stability of99mTc (Sn)-pyrophosphate

The in vitro stability of^99mTc (Sn)-PyP as a function of experimental conditions of the preparation of the kit and time elapsed after labeling has been tested. The preparation was protected by using nitrogen-purged reactant solutions and kit vials and by ascorbic acid. The samples under nitrogen are stable for 6 h when the content of^99mTc-pertechnetate raises to 5%. The best stability was achieved by addition of 5 g of ascorbic acid per ml of the kit (content of^99mTc-pertechnetate about 0.5%). To accelerate the decomposition, exogenous hydrogen peroxide was used. In this case it was found that the presence of 10 g of ascorbic acid inhibits the effect both of oxygen and peroxide (6 g H₂O₂/ml of the kit). Radiochemical purity of^99mTc (Sn)-PyP remains practically unchanged for 6 h (content of^99mTc-pertechnetate about 0.5%).     

In vitro and in vivo studies of99mTc IgG: A comparison between three labeling methods

Polyclonal immunoglobulin IgG was labeled using three different methods: a direct method via 2-mercaptoethanol, an indirect one, in which a chelating group was covalently attached to the protein and the^99mTc added as a glucoheptonate complex and a photoactivation method. The properties of^99mTc polyclonal antibody labeled by three different methods were assessed by in vitro and in vivo studies. The ratio between inflamed thigh to normal thigh was similar and independent of the method of labeling.     

Control scintigrams of rat organs with 99mTc labeled compounds

The control scintigrams of four kinds of organs in rats with 99mTc were presented by the Kaneko's method using the improved pinhole collimator. All images were high resolutive, and the fine structures of the organs were found in them.     

The quality of99mTc eluates

The possible effects of several protecting procedures on the quality of^99mTc eluates were investigated. The content of⁹⁹Mo in the eluates (⁹⁹Mo breakthrough) was expressed in (%) with respect to the total adsorbed⁹⁹Mo radioactivity and in () i.e. as the ratio of⁹⁹Mo and^99mTc radioactivities in each particular eluate. The radiochemical purity was expressed in (%) of^99mTc(VII) in the eluates. The content of Al³⁺ and Cu²⁺ as chemical impurities was also determined.     

Configurational stability in some 3-coordinate phosphorus compounds

PMR spectra of a variety of 4,4,5,5-tetramethyl-1,3,2-dioxaphospholanes, bearing different substituents at phosphorus, have been determined at different temperatures. There is no inversion at phosphorus detectable. The P-chloro compound undergoes a chemical exchange process the rate of which is concentration dependent.     

Bridging the gap between in vitro and in vivo imaging: isostructural Re and 99mTc complexes for correlating fluorescence and radioimaging studies

A bifunctional ligand that is capable of forming Re and 99mTc complexes as complementary fluorescent and radioactive probes was developed. The tridentate bis(quinoline) amine ligand, which is referred to as the SAACQ system, was prepared in a single step from Fmoc protected lysine in high yield. Reaction of the SAACQ ligand with [Re(CO)3Br3]2- resulted in the formation of the SAACQ-(Re(CO)3)+complex which exhibits favorable fluorescence properties including a long lifetime and a large Stoke's shift. Because the SAACQ ligand is derived from an amino acid, it can readily be linked to or incorporated within peptides as a means of targeting the probe to specific receptors. To demonstrate this feature, the SAACQ ligand and the SAACQ-Re complex were incorporated into fMLFG, a peptide that binds to the formyl peptide receptor (FPR). Uptake of the fMLF[(SAACQ-Re(CO)3)+]G conjugate into human leukocytes in vitro was visualized by fluorescence microscopy, and the observed distribution of the peptide was similar to that of a well-established fluorescent FPR probe. The corresponding Tc complex, fMLF[(SAACQ-99mTc(CO)3)+]G, was prepared in excellent yield from [99mTc(CO)3(OH2)3]+, which affords the opportunity to correlate the results of the microscopy experiments with in vivo radioimaging studies because the probes are isostructural.     

Preparation of99mTc complexes with compounds structurally related to ethylene diamine tetraacetic acid

The preparation of^99mTc-Sn-DOTA,^99mTc-Sn-DDDTA and^99mTc-Sn-DHDTA is described. The labelling efficiency of all samples was checked by paper chromatography, thin layer chromatography and paper electrophoresis. Preliminary results of the biodistribution studies performed in white rats are given.     

Rapid estmation of technetium in99Mo−99mTc generators

A nomogram is presented to estimate the radiooctivity of^99mTc in⁹⁹Mo−^99mTc generators, based on equations of radioactive equilibrium. Since the parent element decays through two isomeric states of the daughter, the ratio of the total mass of technetium per millicurie of^99mTc is a function of the time elapsed between two consecutive elutions. Values of the amount of^99mTc expressed as a mole fraction or in moles or grams of total technetium per millicurie of^99mTc^m are also presented.     

Radiochemical purity of99mTc radiopharmaceuticals

Some factors which could adversely affect the integrity of eight routine^99mTc radiopharmaceuticals have been investigated. The radiochemical purity of the preparations was determined both under standard (reconstitution according to the manufacturer's instructions) and under experimental conditions (higher contents of longlived⁹⁹Tc and copper). The influence of radiolytically produced hydrogen peroxide as well as the effect of introduction of air during the addition of pertechnetate as an example of poor labeling technique were examined. The radiochemical analyses were performed by paper and TL chromatography and electrophoresis.     

Chemical and biological evaluation of 99mTc (CO)3 and 99mTc complexes of some IDA derivatives

The confirmation that N-substituted imidodiacetic acids, as small and simple ligand systems containing amines and carboxylic acids, could be coordinated to the tricarbonyl core and form inert complexes with [^99mTc (CO)₃(H₂O)₃]⁺, is demonstrated. The HPLC quality control results of ^99mTc-carbonyl tagged IDA molecules, performed by gradient HPLC, have shown that HIDA, EHIDA and p-butyl-IDA form complexes with [^99mTc(CO)₃(H₂O)₃]⁺, with a labeling yield of ~90% for each of ^99mTc(CO)₃ IDA derivatives. However, the changes in the structure of labeled compounds, e.g., EHIDA, influence the changes in the biological behavior. In comparison with ^99mTc-EHIDA, the biliary excretion of ^99mTc(CO)₃ EHIDA was lower, but the urinary excretion higher. This revised version was published online in July 2006 with corrections to the Cover Date.     

Desorption of99Mo from spent99Mo/99mTc generator

A simple method for desorption and purification of⁹⁹Mo from spent⁹⁹Mo/^99mTc generators is described. The alumina column was washed successively with 0.9% saline water, 35% H₂O₂, and then the⁹⁹Mo was eluted with 2M NH₄OH. Ammonia and residual H₂O₂ were removed by heating the eluate. Finally,⁹⁹Mo solution was passed through a 0.2 m membrane filter to remove precipitated aluminium hydroxide.     

99mTc-centered one-pot synthesis for preparation of 99mTc radiotracers

Nuclear medicine relies on two main imaging modalities: single photon emission computed tomography (SPECT) and positron emission tomography (PET). Radiopharmaceuticals (or radiotracers) are the blood stream of nuclear medicine for the diagnosis or therapy of diseases. Diagnostic radiotracers that are small molecules labelled with a gamma-emitter for SPECT or positron-emitter for PET provide a non-invasive method to assess the disease or disease states and monitor the therapeutic efficacy of a specific treatment regime. Over the past four decades, radiopharmaceutical research has been practising one-pot synthesis at the tracer level (10(-7)-10(-6) M). Many (99m)Tc radiotracers currently used in nuclear medicine are routinely prepared by following the basic principles of one-pot synthesis. Unlike traditional organic one-pot synthesis, which often involves the formation of multiple C-C and C-heteroatom bonds in a single step, the (99m)Tc-centered one-pot synthesis requires the formation of multiple coordination bonds between Tc and various donor atoms, such as N, O, S and P. This review will illustrate how the (99m)Tc-centered one-pot synthesis is utilized for routine preparations of different (99m)Tc radiotracers.     

Preparation of salicylidene-aminates labeled with99mTc

A series of bidentate and tetradentate ligands with azomethine and Ar–OH functional groups derived from salicylaldehyde and primary alkyl or aryl monoamines and diamines has been synthesized and labeled with^99mTc at various pH's using stannous chloride as reducing agent. The labeling efficiency was monitored by thin layer and paper chromatography.