Assessment of 99mTc-succimer residual activity using inert nonreactive syringes.

UNLABELLED: It has been widely reported that (99m)Tc-succimer adsorbs to plastic syringes significantly (up to 50%), often resulting in a lower administered dose than intended or inaccurate dosing. This adsorption rate is especially problematic in the pediatric population. To improve (99m)Tc-succimer dosing, we compared the adsorption of (99m)Tc-succimer with 2 types of syringes: silicone-coated syringes with nonlatex rubber on the plunger and inert nonreactive syringes with no silicone coating and no rubber on the plunger. METHODS: (99m)Tc-succimer kits were compounded according to the manufacturer's instructions. (99m)Tc-succimer doses (37-185 MBq) were drawn into 3-mL (silicone-coated or inert nonreactive) syringes in a 1-mL volume. Thirty min, 1 h, 2 h, and 4 h later, the syringes were assayed in a dose calibrator and assayed again after being emptied and rinsed with saline. In addition, we examined the data collected from 129 (99m)Tc-succimer doses administered in a pediatric department, in which 52 were dispensed in silicone-coated syringes and 77 were dispensed in inert nonreactive syringes. The doses were assayed immediately before and after injection. The syringes were flushed with normal saline. RESULTS: The labeling efficiency of the (99m)Tc-succimer kits was more than 95%. Residual activity left in the inert nonreactive syringes was 0.73% (SD, ±0.18%), which was significantly lower than the activity left in the silicone-coated syringes, 20.9% (SD, ±5.6%; P < 0.0001). The extent of adsorption did not change significantly between 30 min and 4 h of incubation. The clinical data showed that the residual activity was 30.6% (SD, ±12.5%) from doses dispensed in silicone-coated syringes and 6.38% (SD, ±2.95%) from doses dispensed in inert nonreactive syringes (P < 0.001). CONCLUSION: The inert nonreactive syringes had significantly less residual of (99m)Tc-succimer than silicone-based syringes, making it possible to accurately administer calculated doses of (99m)Tc-succimer to pediatric patients.

Retention of 99mTc-DMSA(III) and 99mTc-nanocolloid in different syringes affects imaging quality.

(99m)Tc-dimercaptosuccinic acid [DMSA(III)] and colloidal human serum albumin ((99m)Tc-nanocolloid) are widely used radiopharmaceuticals. Recently, in our institution we encountered image quality problems in DMSA scans after changing the brand of syringes we were using, which triggered us to look into the adsorption properties of syringes from different brands for (99m)Tc-DMSA(III) and (99m)Tc-nanocolloid. We also describe a clinical case in which adsorption of (99m)Tc-DMSA(III) caused inferior imaging quality. DMSA and nanocolloid were labeled with (99m)Tc following manufacturer guidelines. After synthesis, syringes with (99m)Tc-DMSA(III) and (99m)Tc-nanocolloid were stored for 15, 30, 60, and 120 min. We evaluated Luer Lock syringes manufactured by different brands such as Artsana, Henke-Sass-Wolf, B. Braun Medical N.V., CODAN Medizinische Geräte GmbH & Co KG, Becton Dickinson and Company, and Terumo Europe. Adsorption of (99m)Tc-DMSA(III) and (99m)Tc-nanocolloid was acceptably low for all syringes (<13%), except for two brands with (99m)Tc-DMSA(III) adsorption rates of 36 and 30%, respectively, and for one brand with a (99m)Tc-nanocolloid adsorption rate of 27%. Adsorption of (99m)Tc-DMSA(III) and (99m)Tc-nanocolloid reaches critical levels in syringes produced by two brands, potentially causing poor image quality--for example, in DMSA scans using pediatric radiopharmaceutical doses. It is advised to check the compatibility of any radiopharmaceutical with syringes as an integral part of the quality assurance program.

Preparation and evaluation of (99m)Tc-DMSA lyophilized kit for renal imaging.

Dimercaptosuccinic acid (DMSA) has been evaluated and used with technetium 99m ((99m)Tc) in imaging of kidneys. DMSA lyophilized kits were prepared and radiolabelled with (99m)Tc. Paper and thin-layer chromatography have been employed using various eluent systems for the radiochemical analysis, percentage labeling and binding capacity of (99m)Tc-DMSA. Female albino rabbits were used for this study. Biological data obtained after intravenous injection of radiolabelled DMSA to female albino rabbits revealed 32.42% uptake and long retention time in the kidneys. On the basis of animal biodistribution data, it is suggested that DMSA when labeled with (99m)Tc is useful complex for renal imaging and can be successfully applied as a diagnostic tool in nuclear medicine. Clinical biodistribution and radiation dosimetry studies are planned in future.

Biokinetics and dosimetric studies about 99mTc(V)-DMSA distribution.

Research for radiodiagnostic agents should considerate biological critical parameters which will give own contribution on the absorbed dose. The dimercaptosuccinic acid (DMSA) labeled with (99m)Tc(V) is a radiopharmaceutical which has well established role in medullar thyroid carcinoma and has been proposed in evaluation of bone metastasis. This work studied the biokinetics and dosimetry of (99m)Tc(V)-DMSA by animal model. The (99m)Tc(V)-DMSA was prepared from a (III)DMSA kit alkalized. Mice (n=5) received (99m)Tc(V)DMSA i.v., they were sacrificed (30 min, 1h, 5h and 12h), the organs excised and the activities measured by a gamma counter. The results were evaluated based on %activity/g and the absorbed dose was estimated (MIRDOSE 3.0 program) by extrapolation of data from animal to human scale. The results showed the majority of organs reached the top uptake at 30 min, the greatest kidney uptake was (4.81 +/- 1.38)% activity/g, while the bone presented its highest uptake at 1h (5.49+/- 0.47)% activity/g, after 1h all the organs had activity exponential decrease. The biokinetic profile of (99m)Tc(V)-DMSA was well established, allowing quantifying of residence time, and the radiation dose estimates were made for this agent. About the absorbed dose, the preliminary results showed higher value to bone, being the soft tissue dose relatively low.

The role of Tc-99m (V) DMSA scintigraphy in the diagnosis and follow-up of lung cancer lesions.

OBJECTIVE: To define the role of Tc-99m (V) dimercaptosuccinic acid (DMSA) scanning in the detection of lung cancer (LC) and its metastases, and monitoring the response of LC lesions (LCL) to chemo/radiotherapy (TH). METHODS: Tc-99m (V) DMSA whole-body scans, planar thorax views, and thorax Single-photon emission computed tomography (SPECT) images were obtained both 30 min (early) and 5 h (late) after Tc-99m (V) DMSA administration in 12 small/nonsmall cell LC patients (11 men, 1 woman; mean age 59 years). Five patients also had bone scans. The same scintigraphic protocol was performed in 7 of 12 patients, 3 weeks after first-line TH. TH response was evaluated visually in all LCL and semiquantitatively in primary tumors (PT) of six patients, by comparing the tumor uptake ratios (TUR) of pre-TH and post-TH Tc-99m (V) DMSA SPECT [TUR = mean counts of region of interests (ROI) in PT/mean counts in contralateral ROI]. In seven patients, a 6-month survival was determined. RESULTS: Tc-99m (V) DMSA accumulated in 34 LCL (11 PT, 19 bone metastases, 1 suprarenal mass, 1 axillary node, 2 supraclavicular nodes). A total of 11 patients displayed Tc-99m (V) DMSA uptake in LCL and one patient did not show uptake. In six patients, SPECT imaging showed deeply located PT in the lung parenchyma better than planar views. In five patients, both planar and SPECT views revealed peripherally located PT in the lungs. Early scans showed 18 LCL and late scans displayed all the LCL. Nine bone metastases on pre-TH Tc-99m (V) DMSA scans revealed matched areas of increased Tc-99m methylene diphosphonate (MDP) uptake on bone scans; six bone metastases were additionally detected on Tc-99m (V) DMSA scans when compared with bone scans, and four bone metastases on Tc-99m (V) DMSA scans could not be compared with bone scans because bone scan was not performed. In one patient, Tc-99m (V) DMSA scans became positive for bone metastases on post-TH later than the bone scans for some of the bone metastases. Neither planar nor SPECT imaging showed mediastinal lesions defined on thorax CT in nine patients. On TH monitoring, 17 LCL showed diminished Tc-99m (V) DMSA uptake, one disappeared, four were unchanged, three displayed increased uptake, and five new lesions were established. Of the six patients, TUR in PT increased in two (one survived), decreased in one (exitus), was unchanged in two (two exitus) on post-TH scans, and PT totally disappeared in one (survived) patient. CONCLUSIONS: Tc-99m (V) DMSA scans are useful in detecting LCL, except for those around the blood pool regions, making it a promising modality to monitor TH response. Obtaining a single fifth hour late Tc-99m (V) DMSA scan is appropriate. SPECT should be applied to all patients for the detection of deeply located lesions.

Morphology and release kinetics of technetium-99m(V) dimercaptosuccinic acid loaded, poly(lactic-co-glycolic)acid microspheric delivery system. An experimental approach that may be used for targeted radiation treatment.

The aim of our studies was to formulate a system that delivers the required radiation dose to the tumor site and minimize the harm to other organs or tissues. The poly (lactic-co-glycolic acid, 75:25; 50:50) microspheric radiation delivery system was fabricated using double emulsion solvent evaporation technique for the encapsulation of technetium-99m(V)dimercaptosuccinic acid ((99m)Tc(V)DMSA). Microspheres of different sizes (0.2-20.0 mum) were prepared. The initial burst in microspheres with 10% and 1% poly vinyl alcohol (PVA) in the presence of poly ethylene glucol (PEG) was as 30% and 16% respectively, however the initial burst in microspheres without the PEG was 9% and 1.2% respectively. The results indicated that smaller microspheres had higher encapsulation (68%) of (99m)Tc(V)DMSA than larger microspheres (15%). The stirring rate changed the surface of the microspheres from smooth spherical, to spherical, porous. The ratio of co-polymers (75:25/50:50) affected the release kinetics. In conclusion, our studies with varied surfactant concentrations, co-polymer concentrations and speed of solvent evaporation, on the morphology and release kinetics of (99m)Tc(V)DMSA from the microspheres, may be applied for the fabrication of targeted radiotherapeutic microspheres by substituting (99m)Tc(V)DMSA with rhenium-188 (V) DMSA ((188)Re(V)DMSA). (188)Re(V)DMSA is a therapeutic analogue of (99m)Tc(V)DMSA and both share similar radiopharmaceutical properties.

Evaluation of stannous oxidation in the preparation of ultrahigh-purity 99m Tc(V)-DMSA.

It has been shown previously that renal kit, trivalent technetium-99m dimercaptosuccinic acid [99mTc(III)-DMSA], can be transformed into tumour imaging agent, pentavalent technetium-99m DMSA [99mTc(V)-DMSA], by adding sodium bicarbonate (NaHCO3) and subsequently bubbling with oxygen. However, the purity of this pentavalent preparation was reported to be in the range 83-94% at best. In this study, the preparation of ultrahigh-purity 99mTc(V)-DMSA is described, and the role of stannous oxidation in the conversion of 99mTc(III)-DMSA to 99mTc(V)-DMSA is evaluated in order to understand the underlying mechanism. The results show that controlled oxygen bubbling increases the 99mTc(V)-DMSA levels, with a concomitant decrease in the 99mTc(III)-DMSA levels, in a time-dependent pattern. The purity of the pentavalent DMSA is shown to be consistently very high (>99%), as estimated by chromatography, and this correlates very well with the minimal or no renal uptake of this compound in patient studies.

pH sensitive properties of Tc(V)-DMS: analytical and in vitro cellular studies.

Numerous clinical studies with the pentavalent technetium complex of dimercaptosuccinic acid [Tc(V)-DMS] seem to indicate its new role in nuclear oncology. Thus, we questioned what properties of the Tc(V)-DMS molecule associate with its tumoral tissue accumulation. Because studies have reported tumor tissue to be more acidic than normal tissue, acidification might be related to the Tc(V)-DMS localization in tumor tissue. Thus, in the present study, a working hypothesis drew to test the acidification as a plausible factor, and various analytical methods and an in vitro cellular system using Ehrlich ascites tumor cells (EATC) implemented. Analytical methodologies demonstrated the decrease of the overall negative charge of the Tc(V)-DMS molecule, promoted by the acidification of the analytical medium and the sample dilution. In the in vitro cellular experiment, acidification alone showed no effect on the radioactivity accumulation in EATC; nevertheless, if accompanied by a pre-dilution of the Tc(V)-DMS sample added into the cell incubation media, cellular radioactivity accumulation was observed. Thus, acidification as a mediator for the Tc(V)-DMS accumulation in tumoral cells, concurrently with dilution as the promoter of the process, constituted the foundation for discerning the working hypothesis.

Adsorption of some technetium-99m radiopharmaceuticals onto disposable plastic syringes.

OBJECTIVE: The purpose of this study was to determine the adsorption behavior of some widely used, commercially available 99mTc radiopharmaceuticals onto different types of plastic syringes. METHODS: Kits were reconstituted with 99mTc-pertechnetate diluted with 0.9% saline to produce maximum radioactive concentrations, as stated by the manufacturers. Aliquots of the solutions were transferred to four different brands of 2-ml syringes. The activity in the syringes was measured before and after injections or simulated injections. The amount adsorbed to the plastic syringe barrel and plunger before and after washout also was measured at different time intervals. Comparisons between products from different manufacturers were made for 99mTc succimer (DMSA) and 99mTc macroaggregated albumin (MAA). RESULTS: Some 99mTC preparations undergo significant adsorption to plastic syringes. Adsorption differs considerably between products from different manufacturers. There was significantly higher residual activity in some types of syringes. In some cases the residual was as high as 40%-50% of the initial activity, and most of the adsorption occurred within 15 min of filling the syringe. CONCLUSION: The data suggest that the extent of adsorption depends on pharmaceutical excipients in the kits and/or the type of syringe used. When inappropriate syringes are used, the reduction in the administered activity may result in poor-quality images. Therefore, the compatibility between radiopharmaceutical and syringe should be investigated under normal conditions of preparation and use every time a new brand of syringe or a new radiopharmaceutical comes into use in diagnostic nuclear medicine.

Pentavalent 99Tcm-DMSA imaging in patients with bone metastases.

Pentavalent 99Tcm-dimercaptosuccinic acid (99Tcm-(V)DMSA) has an established role in imaging medullary thyroid carcinoma. There have been case reports of uptake in bone metastases. Our aims were to compare 99Tcm-(V)DMSA with 99Tcm-hydroxymethylene diphosphonate (99Tcm-HDP) in bone metastases, to assess its value in imaging of bone metastases, and to assess the prospects of the beta-emitting analogues 186/188Re-(V)DMSA as palliative agents for painful bone metastases. Ten patients confirmed by a 99Tcm-HDP bone scan to have bone metastases secondary to carcinoma of the prostate, lung or breast were injected with 99Tcm-(V)DMSA (600 MBq). Whole-body scans acquired at 3 and 24 h were compared with the 99Tcm-HDP bone scans. 99Tcm-(V)DMSA showed high soft tissue background, kidney retention and avid uptake in most bone metastases: 86% of bone lesions identified on bone scans were detected with 99Tcm-(V)DMSA. The lesion-to-normal ratios were comparable to or lower than those for 99Tcm-HDP at 3 h, but increased by 24 h. Instances of abnormal uptake in liver, primary lung tumour, lymph nodes and pleural effusion were observed. We conclude that 99Tcm-(V)DMSA is a tracer for bone metastases (with lower sensitivity than 99Tcm-HDP) and soft tissue tumours. If 186/188Re-(V)DMSA behave similarly, they may find use in therapy for soft tissue tumours and bony metastases.