Quality control of colloid and particulate 99mTc-labeled radiopharmaceuticals

A procedure for the radiochemical purity control of colloid and particulate 99mTc-labeled radiopharmaceuticals is described. The proposed technique is based on the use of two chromatograms, using in both, 15% H3PO4 as solvent and impregnated glass fiber media (Gelman ITLC type SG) as stationary phase. A pretreatment of the radiopharmaceutical with 6 N NaOH is involved prior to one chromatographic run. The procedure is fast and the different species (free pertechnetate, 99mTc-Sn-colloid and labeled 99mTc) in a 99mTc-labeled radiopharmaceutical can be determined accurately and with reliability.     

Quality control of colloid and particulate 99mTc-labeled radiopharmaceuticals

A procedure for the radiochemical purity control of colloid and particulate ^99mTc-labeled radiopharmaceuticals is described. The proposed technique is based on the use of two chromatograms, using in both, 15% H₃PO₄ as solvent and impregnated glass fiber media (Gelman ITLC type SG) as stationary phase. A pretreatment of the radiopharmaceutical with 6 N NaOH is involved prior to one chromatographic run. The procedure is fast and the different species (free pertechnetate, ^99mTc-Sn-colloid and labeled ^99mTc) in a ^99mTc-labeled radiopharmaceutical can be determined accurately and with reliability.     

The chemistry of 99mTc-labeled radiopharmaceuticals

The subject of the chemistry of 99mTc-radiopharmaceuticals consists of a collection of bits and pieces of information without a unifying theme. Since the initial impetus to the field of organ imaging was provided by radiochemists, nuclear chemists, and clinician-investigators, using easily prepared 99mTc-compounds from available off-the-shelf ligands, complete chemical characterization was not carried for the 99mTc-radiopharmaceuticals and their metabolites. The influx of coordination, organic, and analytic chemists and their systematic studies clarified some of the structures of these tracers, and promoted the general synthetic methods of a variety of ligands and the corresponding 99mTc-chelates as well as understanding of the nature of their metabolites. Although major developments for organ-imaging radiopharmaceuticals had been made, future studies will result in the simplified methodology of protein-labeling, fine-tuning of the currently available radiopharmaceuticals for higher organ-extraction, and replacement of expensive 123I-labeled tracers with the corresponding 99mTc-tracers. In general, the Tc-complexes are thermodynamically less stable and kinetically more labile than the corresponding Re-complexes. The well established chemistry of Re-compounds, the similarity of Tc-chemistry to that of Re compounds, and structure-activity relationships of a few classes of 99mTc-labeled compounds, may promote the development of new generation of 99mTc-labeled radiopharmaceuticals.     

Quality control studies of 99mTc-labeled radiopharmaceuticals by high-performance liquid chromatography

Efficacy of HPLC in the quality control of commonly-used ^99mTc-labeled radiopharmaceuticals has been evaluated using different columns. μ-Bondagel and μ-Bondapak columns were found to be suitable for the separation of ^99mTcO₄⁻ from ^99mTc-labeled HSA and HIDA, respectively. Both of these columns offered marginal utility for DTPA, MDP and PPi.     

Comparative quality control of 99mTc-Pyrophosphate and 99mTc-diphosphonate radiopharmaceuticals

European Journal of Nuclear Medicine and Molecular Imaging - The results of analysis of 99mTc-Pyrophosphate (99mPyP), taken as a representative of the group of compounds having an organic...     

A single-strip mini-paper chromatographic method for rapid purity-control of 99mTc-labeled radiopharmaceuticals

A single-strip miniaturized paper chromatographic method (Mini-PC) was developed using 80%-90% acetone solvent for rapid purity-control of 99mTc-radiopharmaceuticals. Routine 99mTc-radiopharmaceuticals (eight kinds of "kit" made agents) and diluted agents (in which radiochemical impurities might be formed) were analyzed by Mini-PC and other methods. This showed that, compared with the other methods, the Mini-PC technique is useful for the simple and rapid routine analysis of radiochemical impurities of "kit" made 99mTc-radiopharmaceuticals.     

A single-strip mini-paper chromatographic method for rapid purity-control of 99mTc-labeled radiopharmaceuticals

A single-strip miniaturized paper chromatographic method (Mini-PC) was developed using 80%–90% acetone solvent for rapid purity-control of ^99mTc-radiopharmaceuticals. Routine ^99mTc-radiopharmaceuticals (eight kinds of kit made agents) and diluted agents (in which radiochemical impurities might be formed) were analyzed by Mini-PC and other methods. This showed that, compared with the other methods, the Mini-PC technique is useful for the simple and rapid routine analysis of radiochemical impurities of kit made ^99mTc-radiopharmaceuticals.     

Radiochemical purity of routinely prepared 99Tcm radiopharmaceuticals: a retrospective study

Radiochemical purity is an important quality parameter for radiopharmaceuticals. In this study, the radiochemical purity of 2090 samples out of 7000 routine preparations of 20 different 99Tcm radiopharmaceuticals was tested using standard methods over a period of more than 7 years. The mean radiochemical purity was 96.92% (standard deviation = 6.71%). Seventy-four preparations failed to meet radiochemical purity limits; that is, 3.54% of all preparations tested or 1.06% of all preparations in the observation period. The reasons for substandard preparations were mainly related to laboratory-specific conditions. The introduction of a dedicated quality control protocol allowed the elimination of many sources of labelling failures and could reduce the number of administered preparations with an insufficient radiochemical purity. We stress the need for quality control in the preparation of radiopharmaceuticals and provide original radiochemical purity values of routinely prepared 99Tcm radiopharmaceuticals.     

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.     

Quality control of 99mTc-labeled dextran for lymphoscintigraphy

99mTc-labeled dextran has been suggested as a lymphoscintigraphic agent. However, quality-control results from previous studies have been controversial. In this study, the optimal concentration of stannous ion and pH value were determined to obtain maximal labeling. Paper and thin-layer chromatography showed total labeling efficiency as high as 98.4%. Anthrone test of the supernatant of the segments from thin-layer chromatographic strip was performed. Colorimetric determinations verified that dextran was found in the same locations as the peak radioactivity.     

Quality control of 99mTc-labeled dextran for lymphoscintigraphy

^99mTc-labeled dextran has been suggested as a lymphoscintigraphic agent. However, quality-control results from previous studies have been controversial. In this study, the optimal concentration of stannous ion and pH value were determined to obtain maximal labeling. Paper and thin-layer chromatography showed total labeling efficiency as high as 98.4%. Anthrone test of the supernatant of the segments from thin-layer chromatographic strip was performed. Colorimetric determinations verified that dextran was found in the same locations as the peak radioactivty.     

Radiochemical purity studies on 10 radiopharmaceuticals

Ten radiopharmaceuticals in frequent clinical use were examined for their radiochemical purity. Thin-layer chromatography, paper chromatography and electrophoresis were used. The activity of the separated components was measured in a gamma sample changer. The assumed chemical identity of the radiochemical impurities was evaluated by comparing the results with data described in the literature. For all radiopharmaceuticals tested, the radiochemical purity was found to be not lower than the value claimed by the manufacturer and to be in accordance with the requirements of the European Pharmacopoeia as far as those pharmaceuticals are listed therein.     

Radiochemical quality control of 99mTc-labelled immunoglobulin G by immobilised protein A from staphylococcus aureus

Large fractions of immunoglobulin G (IgG) from mammalian species show high affinities for protein A isolated from staphylococcus aureus. The radiochemical purity of ^99mTc-labelled IgG was determined by means of protein A, covalently bound to sepharose, by a column radiochromatographic technique and by a simpler and more rapid technique in vials. Different labelling methods produced different radiochemical purities. Limitations and applications of the testing systems are discussed.     

Distribution of 99mTc-labeled lymphocytes in control and inflamed rats

We studied the in vivo fate of CD8(+) lymphocytes, of naive (CD8(+)CD45RC(bright)) or memory (CD8(+)CD45RC(dim)) phenotype, injected in syngeneic rats, after their sorting and labeling with [(99m)Tc] HM-PAO. By using the scintigrafic method we showed that memory CD8(+) lymphocytes were able to recirculate into liver and lungs. The same method was also successfully used to in vivo study the homing of total blood lymphocytes obtained from inflamed rats.     

Evaluation of alternative rapid thin layer chromatography systems for quality control of technetium-99m radiopharmaceuticals

Whatman 3MM™ and Tec-Control™ systems were evaluated as ITLC-SG alternatives for 99mTc-radiopharmaceuticals. They compare well in accuracy and reproducibility, and are faster and more convenient than ITLC-SG. Tec-Control™ radiochemical purity values for 99mTc-sestamibi were more conservative than ITLC-SG. Full solvent migration was not reproduced for 99mTc-tetrofosmin in Tec-Control™, and for this Whatman 3MM™ is preferred. Developing times were 10–15 min, 7–9 min and ~1 min for ITLC-SG, Whatman 3MM™ and Tec-Control™, respectively. Overall, Tec-Control™ strips are preferred due to speed and ease of use.