A novel amine-dioxime chelator for technetium-99m: synthesis and evaluation of 2-nitroimidazole-containing analogues as markers for hypoxic cells.

A novel amine-dioxime chelator for (99m)Tc has been developed. It offers the advantages of ease of synthesis and flexibility in alteration of lipophilicity. Labeling by stannous reduction of pertechnetate takes place rapidly and efficiently at room temperature and is stable for 24 h. The (99m)Tc:ligand ratio is believed to be 1:2. Seven different alkyl moieties were used to achieve a range of lipophilicities. Three series of compounds were prepared: 2-nitroimidazoles as potential hypoxia-targeting agents, 4-nitroimidazoles as a less easily reduced isomer, and untargeted anilines. In an in vitro model of cellular hypoxia, the 2-nitroimidazole compounds all showed selective accumulation whereas 4-nitroimidazoles showed variable selectivity and aniline showed no selectivity. These experiments demonstrate the potential utility of the 2-nitroimidazole derivatives of the amine-dioxime class of chelator as hypoxia-targeting agents.

Hepatobiliary clearance of intravenous Tc-99m pertechnetate.

The normal biodistribution of Tc-99m pertechnetate includes the thyroid gland, salivary glands, choroid plexus, and gastric mucosa. The primary route of excretion is through renal clearance. The authors describe two cases in which hepatobiliary excretion of intravenously administered Tc-99m pertechnetate was observed during scanning for Meckel's diverticulum as a possible source of gastrointestinal bleeding.

Elution characteristics of 99Tcm-labelled erythrocytes in relation to scintigraphic detection of gastrointestinal bleeding.

Radionuclide imaging for the detection and localization of gastrointestinal bleeding is a highly sensitive and well-established clinical tool. 99Tcm-labelled erythrocytes have permitted the recognition of intermittent bleeding up to 24 h following injection. However, free pertechnetate is actively secreted by gastric mucosa and can result in confounding gut activity. The possibility that pertechnetate may elute from the radiolabelled erythrocytes was investigated in an in vitro model. Blood samples from five subjects undergoing gated cardiac studies were labelled by modified in vivo, modified in vitro and pure in vitro methods and then incubated in serum for 24 h. Automated cell counts and instant thin layer chromatography were used to measure the physical and radiochemical stability of the labelled erythrocytes. No detectable haemolysis occurred and no free pertechnetate was released from the cells. However, an unexpected hydrophilic 99Tcm species became detectable in the supernatant with a quantitative index which increased from an initial value of 0.016 +/- 0.004 to 0.079 +/- 0.012 at 24 h (P less than 0.00001). This index did not differ among the three labelling methods. A chromatographically similar material was identified in the urine of a patient undergoing a gastrointestinal bleed study. The possibility of gut and/or hepatobiliary secretion of this material needs further clarification before delayed positive studies can be relied upon to indicate gastrointestinal bleeding.

Stabilization of [99mTc]HMPAO--1. Ethanolic preparation.

The use of [99mTc]HMPAO for cerebral blood flow imaging has been hampered by the short useful life time of the labelled radiopharmaceutical. Preparation of [99mTc]HMPAO in 85% ethanol was found to increase the in vitro stability (92% radiochemical purity at 90 min) in comparison to the aqueous preparation (79% at 90 min). Biological distribution studies in mice indicated similar brain uptake (4.42 +/- 1.02 and 4.12 +/- 0.82% per gram at 20 min) and brain: blood ratio (0.97 +/- 0.27 and 1.03 +/- 0.20 at 20 min) of the ethanolic (2 h after preparation) and aqueous (15 min after preparation) formulations of [99mTc]HMPAO respectively. The improved in vitro stability of [99mTc]HMPAO prepared in 85% ethanol may prove useful in instances where previously the 30 min time limit precluded its use.

Chemical aspects of labeling sucralfate with 99mTcO4.

Two formulations of [99mTc]sucralfate have been used to image gastric and duodenal ulcers and inflammatory bowel disease. One formulation is a complexation of [99mTc]HSA with sucralfate. The second is prepared by directly labeling sucralfate with [99mTc]pertechnetate in the presence of stannous ion. An in vitro study of the factors affecting the production and stability of these labeled sucralfate preparations was conducted. Both formulations were stable at the acidic pH likely encountered in the stomach. However, at pH greater than 6 the albumin-sucralfate complex began to dissociate while directly labeled sucralfate was stable to a pH of 9. Conversely it was shown that directly labeled sucralfate was more susceptible to loss of 99mTc to other chelating species. Sucralfate complexed with [99mTc]HSA was radiochemically stable up to a specific activity of 26 GBq (700 mCi) per gram while directly labeled sucralfate showed decreased 24-hr stability at specific activities greater than 837 mCi (31 GBq) per gram.

Interaction of some sterilizing filter materials with some technetium-99m radiopharmaceuticals.

The retention of a variety of 99mTc radiopharmaceuticals on four different sterilizing filter membranes has been evaluated. It was demonstrated that some 99mTc radiopharmaceuticals show significant retention of certain types of sterilizing filters, presumably due to interactions between the radiopharmaceutical and the filter material.

Mechanistic aspects of the interaction of 99mTc in association with stannous pyrophosphate with damaged red blood cells.

The binding of the various components of [99mTc] stannous pyrophosphate and stannous pyrophosphate/pertechnetate to damaged red blood cells is studied. It is shown that the pyrophosphate molecule enters the damaged red blood cells when the pyrophosphate concentration in blood is greater than 100 nmol/ml but does so as the uncomplexed ion. Uptake of 99mTc when introduced as [99mTc]stannous pyrophosphate is constant at approximately 18%. If the 99mTc is introduced as pertechnetate after the damaged cells are mixed with stannous pyrophosphate then at low stannous ion concentrations the uptake is directly dependent on the stannous ion concentration. However, at higher stannous ion concentrations the uptake of technetium by the damaged red cells decreases, but this decrease appears to result from several independent aspects of the sample, such as the binding of the technetium to the plasma proteins and the displacement of the technetium by pyrophosphate within the damaged cell.

Some factors affecting the calibration of radionuclide calibrators--I. 99mTc.

In the Winnipeg area a centralized radiopharmacy serves several Nuclear Medicine departments supplying all their 99mTc radiopharmaceuticals on a daily basis. It was observed that there was very poor consistency between the assays as determined by the Radiopharmacy and those determined in the various Nuclear Medicine departments. An attempt to "correct" the various calibrators using a 57Co "mock" 99mTc source resulted in an aggravation of the problem, and an investigation of relative responses of various calibrators to the "mock" relative to a 99mTc source was undertaken, together with an investigation of the influences of various environmental conditions on the calibrator function. In many Nuclear Medicine departments technologists sensitive to concerns of radiation exposure have stacked lead shielding around the calibrator as added protection. However if the calibrator is not calibrated with sufficient lead shielding, such additional shielding will increase the ionization within the chamber, resulting in an elevated assay being obtained due to the lead X-rays and back-scattered radiation. In the absence of lead shielding, similar effects, although smaller in magnitude, are observed from other environmental factors such as the proximity of a wall or a person. Thus in selecting a calibrator, one which comes from the manufacturer, with a calibration certified by the manufacturer, incorporating an adequate amount of lead shielding to prevent additional back-scatter re-entering the ionization chamber should be considered essential unless a complete on-site recalibration using accurately calibrated samples of the radionuclides in question is planned.

Radiation decomposition of technetium-99m radiopharmaceuticals.

Technetium-99m radiopharmaceuticals are shown to be subject to autoradiation-induced decomposition, which results in increasing abundance of pertechnetate in the preparation. This autodecomposition is catalyzed by the presence of oxygen, although the removal of oxygen does not prevent its occurrence. The initial appearance of pretechnetate in the radiopharmaceutical is shown to be a function of the amount of radioactivity, the quantity of stannous ion used, and the ratio of Tc-99m to total technetium in the preparation.

Colloidal particle-size determination by gel filtration.

The particle sizes of technetium-99m sulfur colloid and technetium-99m antimony sulfide colloid are determined by gel filtration. These results are compared with those obtained by electron microscopy and by ultrafiltration. It is shown that gel filtration is suitable for particle-size determination below 100 nm, whereas above this size ultrafiltration provides the most convenient method.

Contamination from 131I, 103Ru, and 239Np in the eluate of 99Mo-99mTc generators loaded with (n, gamma)-produced 99Mo.

Iodine-131, ruthenium-103, and neptunium-239 are present as contaminants in the eluate of 99Mo-99mTc generators loaded with 99Mo prepared by thermal-neutron irradiation of enriched 98Mo. The elution pattern of each of these contaminants is determined, together with the amounts found in the eluate of all generators tested over a 7-month period.