Tc Radiopharmaceuticals Research Articles

Application of a macromolecular Sn (II) complex to the preparation of 99mTc radiopharmaceuticals

AbstractTo develop insoluble Sn2+ complexes for the preparation of 99mTc radiopharmaceuticals, the adsorption of Sn2+ to macroreticular chelating ion exchange resins having various functional groups was investigated. Among them, a resin containing aminophosphonic acid groups showed a high adsorption capacity for Sn2+, which was bound strongly to the resin by chelation. This macromolecular Sn2+ complex was very stable against hydrolysis and oxidation, and could be applied satisfactorily for the reduction of 99mTc.

Quantitative study of the structure-stability relationship of Tc complexes

By studying structural parameters (van der Waals radius and bond length from x-ray crystallography) of more than 100 known Tc compounds and using the cone packing model, a stability indicator of the Tc compounds was derived. The indicator is based on the solid angle factor sum (SAS), which is calculated from van der Waals radii and bond lengths between all coordinating atoms and Tc. The average SAS value is 0.97 ± 0.13. The SAS value reflects the limits of the packing of ligand around Tc. The quantitative calculation of the SAS is useful for predicting stability and designing new Tc radiopharmaceuticals.

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

In the Winnipeg area a centralized radiopharmacy serves several Nuclear Medicine departments supplying all their 99 m Tc 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” 99 m Tc source resulted in an aggravation of the problem, and an investigation of relative responses of various calibrators to the “mock” relative to 99 m Tc 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.

Long-lived 99Tc in generator-produced 99 mTc, its determination and significance

Taking into account the whole “history” of the 99Mo− 99 m Tc generator the amount of long-lived 99Tc contained in generator produced 99 m Tc is calculated. Some differences between the results obtained and those published in the literature were found. The calculation presented is especially useful for predicting the amount of 99Tc in the product of the extraction generator. The absorbed dose due to long-lived 99Tc was estimated for the case of two 99 m Tc radiopharmaceuticals—pertechnetate and EHDP.

Problems associated with stannous 99 mTc- radiopharmaceuticals

Possible reasons for anomalous in vivo behavior of 99 m Tc radiopharmaceuticals are evaluated. The complicated and poorly understood solution chemistry of technetium as well as tin (II), the most widely used reducing agent, is shown to contribute to problems. Unreliable performance of stannous kits is deduced to be partly due to initial oxidation and hydrolysis of tin (II) as a result of poor formulation, and also due to low stoichiometric ratios of complexing agent to tin. The kits could fail in two ways: (1) only a fraction of the original tin may be available in the desired form at reconstitution; (2) undesirable side reactions of tin and technetium may occur. Evaluation of generator as well as instant technetium has occasionally revealed situations where the carrier content of 99 m Tc solutions could exceed the reductive capability of the stannous ion; this becomes critical with kits containing a very small quantity of Sn (II) in the “usable” form. Parameters for effective performance of tin (II) containing kits are examined, and a titration method allowing for in vitro evaluation of available kits is presented. A model procedure for preparing stable Sn (II) kits has been developed.

Chemistry of technetium 99m

The detection of a number of impurities in 99m Tc effluents from 99 Mo generators is important for proper use of the generator systems. Their identification is described in this review. Technetium in sulfur colloid is probably present as Tc 2 S 7 . Reduction of the technetium by sodium thiosulfate (before acidification) will interfere with the preparation of this compound. In the labeling of serum albumin with 99m Tc in a zirconium electrolytic cell, the pertechnetate is reduced by the zirconium. Successful serum albumin labeling procedures, with a variety of reducing agents, require acidification of the mixture of albumin and reduced technetium to about pH 2. This is believed to be associated with a number of reversible structural changes in the protein. Evidence for pertechnetate Tc in labeled serum albumin is not convincing. Experiments with 99m Tc at the millimolar level suggest that stannous chloride in excess reduces pertechnetate in DTPA solution to the trivalent state and in citrate solution to the quadrivalent state. The reduced technetium is in the form of a dimer, probably with an oxygen or hydroxyl bridge between two Tc atoms, in renal scanning agents processed on the reduction of pertechnetate in the presence of mannitol or sodium gluconate or sodium glucoheptonate. Quality control of Tc radiopharmaceuticals is a difficult problem. Pitfalls in the use of a single technique such as anion-exchange resins or 85% methanol in paper chromatography are discussed in this review.