Rapid determination of oxidation state of unbound 99mTc and labeling yield in 99mTc-labeled radiopharmaceuticals.

Current techniques for determining the radiochemical purity of 99mTc-labeled radiopharmaceuticals are limited by the variety of compounds that can be tested or the length of time required to complete the test. A chromatographic method, based on the use of two solvents (0.9% saline and acetone) and a stationary phase made of silica-coated cellulose strips, solves these problems for water-soluble 99mTc-labeled radiopharmaceuticals. With this method, the oxidation state of unbound 99mTc and the labeling yield of 99mTc-labeled radiopharmaceuticals can be quickly determined: the whole procedure takes only a few minutes to run. This system compares favorably with lengthier procedures and with a commercially available kit.

Technetium-99m labeling of human monocytes for chemotactic studies.

Although the current use of 51Cr for the evaluation of monocyte chemotaxis has yielded encouraging results, certain properties of this radionuclide leave room for improvement. Technetium-99m was evaluated as an alternative label for this purpose. A cell loss of 50% was found, but the recovered cells showed excellent viability and function. Chemotaxis was measured using a modified Boyden's chamber and a lymphocyte-derived chemotactic factor. The chemotactic properties of 99mTc-labeled human monocytes were preserved, and an excellent correlation between radioactive measurement and microscopic counting of migrating cells was observed.

Evaluation of labeling procedures and in vivo stability of 99mTc-red blood cells.

Stable labeling of red blood cells (RBCs) with 99mTc, in yields of about 66%, was achieved by using stannous chloride as a reducing agent. In a study of 12 patients, the stability of technetium-labeled RBCs in the circulation varied significantly among individuals, but the average biologic half-life of the labeled cells was 16.8 hr. Although the labeling yield was lower when the labeling was carried out without EDTA with the addition of stannous chloride after the pertechnetate, this sequence appears to be the best for labeling RBCs for use in obtaining images of the blood pool or the cardiovascular system because of the increased viability of the RBCs.

Radionuclide venography: significance of delayed washout; visualization of the saphenous system.

Venograms were obtained on dogs in which venous thrombosis had been surgically induced. Radionuclide venograms, obtained after injection of 99mTc-labeled microspheres or macroaggregated albumin, showed decreased radioactivity over the areas of venous thrombosis and increased radioactivity over areas of venous stasis. Scintigrams of veins excised after an injection of labeled particles did not delineate thrombi, areas of crush-injured vein, or the venous valves. Delay in the washout of radioactivity on a venogram indicates stasis due to impeded venous flow in the area of thrombosis. A modified technique was developed to obtain simultaneous images of the superficial and deep veins of the leg. Visualization of the superficial veins not only permits detection of superficial abnormalities, but also assists interpretation of the venographic observations of the deep veins.

Efficiency of in vivo labeling of red blood cells with 99mTc.

The effectiveness of three commercial bone scintigraphic agents and freshly made stannous chloride in labeling erythrocytes with 99mTc was compared. Our results indicate that tin pyrophosphate is the agent of choice and that it is most effective when injected at least 15 minutes before the 99mTc-pertechnetate is administered. This technique of labeling red blood cells in vivo could be applied in performing blood pool studies.

Effect of chemical and radiochemical impurities from eluants on 99mTc-labeling efficiency.

Occasionally, radiopharmaceuticals prepared from the eluates of 99Mo-99mTc generators that have not been eluted for several days contain large amounts of free pertechnetate, as tested by radiochromatography and biologically by administration to patients. We fing the most probable causes of poor 99mTc-labeling in these cases to be: a) the presence of a large concentration of 99TcO4-in eluants; b) insufficient stannous ions available for the complete reduction of Tc due to spontaneous oxidation of Sn in the vial and also due to oxidation of stannous ions by the presence of larger than expected concentrations of H2O2 and HO2 radicals in the eluant.

Absorbed radiation dose from radionuclidic impurities in several 123I-labeled radiopharmaceuticals.

The radiation dose to patients from RISA, sodium iodohippurate, and rose bengal labeled with commercially available 123I and its accompanying radioimpurities has been studied. The extra radiation dose to target organs was found to range from 29% to 97% that due to 123I alone when the radiopharmaceutical is administered at calibration time. Additional delay in the time of administration increases the relative impurity dose.

Dose calibrator readings due to radionuclidic impurities found in radiopharmaceuticals.

The influence of the radionuclidic impurities in radiopharmaceuticals on the reading of sample activities in a dose calibrator has been studied. As a practical example, commercially available 123I was used to measure the effect of radioactive impurities on "dose calibrator" readings. The impurities present in commercially available 123I were identified and quantified by the use of a Ge(Li) detector, and the response of a dose calibrator to each impurity was determined. The contribution of radioactive impurities to sample readings was determined for each sample of 123I studied. It was found that impurities may increase the dose calibrator readings up to 31%, even though the impurities were within the warranty given by the manufacturer.

Radiopharmacology. (The state of the art).

The past, present and future development of radiopharmacology as a new branch of science is being presented. Radiopharmacological techniques have been applied by many scientists in the past, not knowing that they were developing a new scientific field. With the advancement of these techniques, the creation of a specialized teaching program and the organization of the first international symposium on radiopharmacology, the first specialized meeting in this area, radiopharmacology became a discipline standing on its own feet. The main purpose of radiopharmacology is to study the chemical properties of radiotracers, and their interactions with living organisms. In order to promote and further expand this field, an international association of radiopharmacology was created. The main purpose of the association is to congregate all those interested in the uses of radiotracers in biological sciences, including medicine, by the organization of national and international meetings.

Potential use of ascorbic acid as a pituitary and adrenal scintigraphic agent.

The distribution of intravenously administered 14C-ascorbic acid (AA) into various tissues of the dog, and the effect of dexamethasone and ACTH administration on the AA distribution was studied. As a function of time, the differences of 14C-AA distribution between adrenal and surrounding organs become greater, and 24 hours after the administration of the dose, the adrenal to liver ratio, as well as adrenal to kidney, is about 10:1. Also concentration of AA in the pituitary showed a gradual increase and reached its peak between 24 and 48 hours. Dexamethasone administration lowered significantly the uptake of 14C-AA by the adrenals, but did not affect the uptake by the pituitary. Three consecutive days administration of ACTH did not affect the uptake of the drug by either glands, but one single dose of ACTH administered one hour prior to the 14C-AA increased the uptake of AA by both glands. These results indicate that properly labeled AA may be an effective pituitary and adrenal scanning agent. Possible ways of labeling AA without changing its pharmacological properties are suggested.

Tc-99m labeled complexes of aldehydes and glutamate as cholescintigraphic agents.

Tc-99m pyridoxylidene glutamate has proven to be an excellent biliary scanning agent, far superior in many respect to the commonly used I-131 rose bengal. The preparation of the compound as previously reported by Baker et al is too time consuming and requires the use of an autoclave which is not available in most nuclear medicine departments. In our facility, we have been preparing similar compounds using several aldehydes and monosodium glutamate to make labeled complexes having the same pharmacological characteristics. The mixture of monosodium glutamate, aldehyde, and Tc-99m pertechnetate is made slightly alkaline, purged with helium, and placed in a sealed vial. The vial, which is protected by a wire basket, is then heated in a laboratory oven at 130 degrees C for a period of 15 to 20 minutes. During this time, the technetium is reduced to a lower valence state and bound to the complex formed. Chromatographic data show that these compounds are chemically similar to that previously reported. The compounds prepared concentrate in the gall bladder of the rabbit in less than 10 minutes. Kinetic studies have been performed on dogs with a scintillation camera and small digital computer to measure rates of blood clearance, liver and gall bladder uptake, and excretion into the intestine. The aldehyde -- glutamate complex promises to be a useful scanning agent for the diagnosis of biliary and hepatocellular diseases.