A comparison of the tumor-seeking agent Tc-99m(V) dimercaptosuccinic acid and the renal imaging agent Tc-99m dimercaptosuccinic acid in humans

Being aware of the ideal nuclear properties of Tc-99m, our interest has been focused on the design of the (+5) oxidation state Tc-99m(V) dimercaptosuccinic acid (Tc(V)-DMSA) as a tumor-seeking agent. Tc-99m(V) DMSA holds a TcO4(3-) core and, like PO4(3-), has excellent characteristics for tumor uptake, but has a different distribution than the well-known renal scanning agent, Tc-99m DMSA. The differences in chemical behavior of Tc-99m(V) DMSA and Tc-99m DMSA are discussed. Three cases in which neoplasms were studies with Tc-99m(V) DMSA and Tc-99m DMSA are presented. Tc-99m DMSA and Tc-99m(V) DMSA, having a common ligand and tracer but, with the metal ion core in a different oxidation state, the uptake characteristics are altered markedly.     

Analogy between tumor uptake of technetium(V)-99m dimercaptosuccinic acid (DMSA) and technetium-99m-MDP

Sixty patients with a variety of malignant tumors were examined with Tc-99m(V) dimercaptosuccinic acid (DMSA) prepared by modification of a commercially available DMSA kit. Significant uptake of Tc-99m(V)-DMSA was observed in a number of tumors, offering additional clinically useful information. In the majority of cases in this study, however, the benefit of the Tc-99m(V)-DMSA image was limited because of low sensitivity. The most striking observation was the similarity between the tumor concentration of Tc-99m(V)-DMSA and the Tc-99m-MDP uptake in the tumor on the regular bone image. Therefore, patients with Tc-99m-MDP uptake in nonosseous tumor sites on the bone scan may be suitable candidates for tumor imaging with Tc-99m(V)-DMSA.     

Pentavalent technetium-99m DMSA uptake in pseudofractures of osteomalacia

Tc-99m MDP and Tc-99m (V) DMSA images are described from a 49-year-old woman with chronic renal insufficiency complicated by osteomalacia. Clinical, biochemical, and radiologic bone profiles were compatible with osteomalacia. Osteomalacia is a condition associated with disorders in which mineralization of the organic matrix is defective. All bone lesions visualized with Tc-99m MDP also showed increased uptake of Tc-99m (V) DMSA. Tc-99m (V) DMSA accumulation has been reported in many malignant and some benign conditions. Pseudofractures in osteomalacia could be included in the spectrum of benign lesions that accumulate Tc-99m (V) DMSA.     

Myocardial infarct imaging in patients with technetium-99m 2,3-dimercaptosuccinic acid. Superiority of technetium-99m pyrophosphate

Technetium-99m 2,3-dimercaptosuccinic acid (Tc-99m DMSA) has been used successfully for imaging acute myocardial infarction in a canine model. The application in humans, however, has not been previously reported. In order to determine the feasibility of using this agent in clinical studies and to compare the agent to technetium-99m pyrophosphate (Tc-99m PPi), ten patients with proven myocardial infarction were studied. While imaging of transmural infarctions in humans was achieved using Tc-99m DMSA, scores for the Tc-99m DMSA images (1.8 +/- 0.96) were not as high as for Tc-99m PPi (2.5 +/- 0.45) (P less than 0.05). Discordance among four independent interpreters was greater for images obtained with Tc-99m DMSA. The superiority of Tc-99m PPi was evident whether images were obtained early (within 24 hours) or late (within five days). Although DMSA images were not obscured by rib uptake, they were less sensitive (63%) than Tc-99m PPi (97%). A potential advantage of Tc-99m DMSA in imaging acute myocardial infarction is that radiotracer concentration in the infarct occurs primarily in the early postinfarction period. The longer postinfarction that Tc-99m DMSA imaging was attempted, the lower the concentration of radiotracer. Thus, Tc-99m DMSA would not be expected to have the same persistence pattern as Tc-99m PPi into the remote postinfarction period. The persistent positivity of Tc-99m PPi has made it difficult to diagnose reinfarction.     

Scintimammographic findings of in situ ductal breast carcinoma in a double-phase study with Tc-99m(V) DMSA and Tc-99m MIBI value of Tc-99m(V) DMSA

The authors present a case of in situ ductal carcinoma of the breast (DCIS) with no associated mass in a 46-year-old woman examined with Tc-99m MIBI and Tc-99m(V) DMSA scans, which were acquired in separate sessions 10 minutes and 60 minutes after injection. Histologic analysis revealed a small (<1 cm) infiltrating ductal carcinoma located within the DCIS. Mammography showed a cluster of microcalcifications on a very dense parenchymal background. Tc-99m(V) DMSA was characterized as positive for DCIS, especially in the delayed image. Tc-99m MIBI failed to identify the lesions previously noted. In conclusion, Tc-99m(V) DMSA scintimammography seems to have an advantage and could improve the detection of nonpalpable in situ breast carcinomas.     

Tc-99m(V) DMSA imaging. A new approach to studying metastases from breast carcinoma.

Combined Tc-99m MDP skeletal imaging and Tc-99m(V) DMSA whole body scans to detect metastases were performed during the follow-up of 30 patients who underwent surgery for breast carcinoma. Eight patients had normal Tc-99m MDP and Tc-99m(V) DMSA scans and were declared free of metastatic disease, further confirmed by no change in symptomatology over a 1-year follow-up period. Twenty-two patients had positive Tc-99m MDP scans with varied skeletal involvement. Tc-99m(V) DMSA scans showed matched areas of increased radiotracer concentration in bony metastases in 20 of these patients. Tc-99m(V) DMSA concentration was not seen in traumatic vertebral collapse or in coexistent osteoarthritic disease in vertebral metastatic involvement. Interestingly, Tc-99m(V) DMSA showed increased concentration in brain and liver metastases. Pentavalent Tc-99m(V) DMSA appears useful for detecting skeletal and soft-tissue metastases in breast carcinoma, and can improve the specificity of Tc-99m MDP bone scans in screening for bone metastases.     

Uptake of pentavalent technetium-99m dimercaptosuccinic acid in idiopathic synovial chondromatosis

We reported two Tc-99m(V) DMSA scintigrams in patients with idiopathic synovial chondromatosis which affected the metacarpo-phalangeal joint and shoulder joint. Tc-99m(V) DMS A accumulated markedly and diffusely in the tumor. Tc-99m(V) DMSA scintigraphy would be valuable for deciding the optimal site for biopsy.     

The role of Tc-99m (V) DMSA scintigraphy in the evaluation of superscan on bone scintigraphy

PURPOSE: This study evaluated the biodistribution of Tc-99m (V) DMSA in patients with superscans on bone imaging and defined its role in differentiating the underlying cause. METHODS: Nine patients (five with metastatic and four with metabolic bone disease) with classical superscans were entered into the study. All patients had the necessary radiologic and biochemical studies and a final diagnosis was reached accordingly. Tc-99m (V) DMSA scintigraphy was performed 1 week after Tc-99m MDP whole-body bone imaging. RESULTS: In four of five patients with widespread skeletal metastases, Tc-99m (V) DMSA scan showed diffusely increased bone uptake. In the remaining patient, the Tc-99m (V) DMSA scan showed a normal distribution pattern. All patients with metabolic bone disease had increased bone uptake on Tc-99m (V) DMSA scans. CONCLUSION: Tc-99m (V) DMSA shows increased bone uptake in patients having a superscan appearance in metastatic or metabolic bone disease. Tc-99m (V) DMSA imaging may play a role in the evaluation of patients with equivocal bone scan findings for a superscan.     

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.     

Oxygen bubbling can improve the labelling of pentavalent technetium-99m dimercaptosuccinic acid

It has previously been reported that almost all of the trivalent technetium-99m dimercaptosuccinic acid (^99mTc (III) DMSA) present in the labelling product of pentavalent technetium-99m DMSA (^99mTc (V) DMSA) can be changed into^99mTc (V) DMSA by bubbling with pure oxygen. We therefore performed studies in animals (mice) and humans to investigate the effect of such oxygen bubbling on the labelling efficiency of and on the renal uptake of^99mTc. The method of labelling of^99mTc (V) DMSA was that of Hirano. It was found that oxygen bubbling oxidized the contaminated^99mTc (III) DMSA into^99mTc (V) DMSA in vitro and decreased the uptake of radioactivity in the kidney in both animals and humans.     

Imaging of head and neck tumors with technetium(V)-99m DMSA. A new tumor-seeking agent

Tumor scintigraphy, using Tc(V)-99m DMSA was performed on 76 patients with head and neck tumors. In 32 cases, SPECT also was performed. Tc(V)-99m DMSA was found to have a sensitivity of 75% (56 cases), a specificity of 85% (20 cases) and an accuracy of 78% on planar imaging. ECT studies showed accumulation of Tc(V)-99m DMSA in all 25 malignant cases studied. However, in benign tumors, four of seven cases (57%) showed radionuclide uptake. Tc(V)-99m DMSA has superior physical properties to Ga-67 and could be of use in the diagnosis of head and neck tumors.     

Role of technetium-99m N,N-ethylenedicysteine renal scintigraphy in the evaluation of differential renal function and cortical defects

PURPOSE: This study was performed to evaluate the effectiveness of technetium-99m N,N-ethylenedicysteine (Tc-99m EC) in comparison to technetium-99m dimercaptosuccinic acid (Tc-99m DMSA) scintigraphy. Differential renal function (DRF) was calculated by both methods and the cortical-phase images of dynamic Tc-99m EC scintigraphy were evaluated for parenchymal defects. MATERIALS AND METHODS: A total of 62 patients with various kidney disorders ranging in age from 1 to 44 years underwent both Tc-99m DMSA and Tc-99m EC scintigraphy. Tc-99m EC summed images of the cortical phase and Tc-99m DMSA images were evaluated visually and quantitatively. Visual analysis was used to define renal parenchymal abnormalities. Quantitative analysis was used in the calculation of DRF. The Tc-99m DMSA scan was taken as the gold standard, and the summed Tc-99m EC scan findings were compared against it. RESULTS: The images obtained with Tc-99m DMSA and Tc-99m EC scintigraphy revealed 99 and 97 focal defects, respectively. The 2 renal parenchyma defects located in the ventral middle sections remained undetected with Tc-99m EC scintigraphy. DRF of the kidneys in each patient was compared using both radiopharmaceuticals. Highly positive correlation between the differential function of these 2 investigations was found (R = 0.91, P = 0.001). The values of mean DRF of the left kidney on Tc-99m EC and Tc-99m DMSA images were 45.8 +/- 19.1 and 45.0 +/- 20.4, respectively. There were no significant differences (P > 0.05). CONCLUSION: This study suggests that although Tc-99m DMSA scintigraphy remains the gold standard method for evaluating parenchymal abnormalities, Tc-99m EC scintigraphy can be a reliable single-modality study to evaluate renal cortical defects, DRF, perfusion, drainage of the urinary system, and indirect evidence of vesicoureteric reflux with the added advantage of low radiation exposure to the patient.     

Tc-99m pentavalent DMSA scintigraphy in myelofibrosis detection

In a 62-year-old man with medullary carcinoma of the thyroid, a postoperative Tc-99m dimercaptosuccinic acid [(V) DMSA] study was requested. In the Tc-99m (V) DMSA scan. no abnormalities, indicating local recurrence or metastatic disease, were observed. However, there was increased uptake in the spleen and liver and significantly diffusely increased uptake in the bone marrow. The patient also had a history of myelofibrosis and these findings appear to have been the result of this pathology.     

Visualization of uveal amelanotic melanoma with technetium-99m(V) dimercaptosuccinic acid

The possibility of using technetium-99m(V) dimercaptosuccinic acid, Tc-99m DMSA, in the evaluation of uveal amelanotic melanoma was assessed in this study. Both planar and SPECT images clearly demonstrated the tumor. Following confirmation of our results by contemporaneous ultrasonography and MRI the patient was treated with Iodine-125 brachytherapy. In combination with other diagnostic tests, Tc-99m(V) DMSA scintigraphy may play a role in the detection of uveal melanoma and its possible systemic metastases.     

Diagnostic efficacy of technetium-99m pentavalent-dimercapto succinic acid versus gallium-67 citrate, imaging in patients with highly suspected acute bone and joint infections

The purpose of this study was to evaluate and compare the diagnostic efficacy of (99m)Tc(V) dimercaptosuccinic acid ((99m)Tc(V)DMSA) with the (67)Ga-citrare ((67)Ga-C) scintigraphy in patients with suspected bone and joint infection. Thirty one patients, 19 men and 12 women, aged 18-78 y with median age 56 y, with suspected acute bone infection, were enrolled in this study. Besides (67)Ga-C and (99m)Tc(V)DMSA scintigraphy, all patients underwent X-ray radiography and technetium-99m methylene disphosphonate ((99m)Tc-MDP) bone scan for supporting the initial diagnosis. The (99m)Tc-MDP bone scan was considered positive for acute bone and joint infection when all its four scintigraphic phases were positive. Final diagnosis was based on needle aspiration and/or biopsy findings. Sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) were calculated. Our results have shown the following: Seventeen patients (17/31) had histologically confirmed acute bone and joint infections, while the remaining patients had no infection. (99m)Tc(V)DMSA diagnosed bone and joint infections in all positive (17/31) patients while (67)Ga-C in 16/31 patients. Discordant scintigraphic results were observed by (67)Ga-C in 2/31 cases: in one positive case of femur postoperative infection (false negative for (67)Ga-C) and in one case of clinicaly suspected infection in the femur while the patient had a preexisting fracture (false positive with (67)Ga-C). No false negative results were observed with (99m)Tc(V)DMSA. Sensitivity, specificity, PPV, NPV and accuracy were maximum for (99m)Tc(V)DMSA, while for (67)Ga-C were: 94.1%, 93%, 94.1%, 93%, and 93.5% respectively. It is concluded that considering the high sensitivity and specificity of (99m)Tc(V)DMSA in the detection of acute bone and joint infections, the lower radiation dose, the cost and the shorter time spent for the imaging procedure, as compared to (67)Ga-C, (99m)Tc(V)DMSA should be preferred to (67)Ga-C as a bone scan agent for the detection of acute bone and joint infections.     

Technetium-99m-<Emphasis Type="Italic">N,N</Emphasis>-ethylenedicysteine and Tc-99m DMSA scintigraphy in the evaluation of renal parenchymal abnormalities in children

Technetium-99m dimercaptosuccinic acid (Tc-99m DMSA) as a static renal agent is currently the most frequently used agent in the detection of renal scarring, and allows accurate calculation of differential renal function (DRF). But this agent has some disadvantages such as relatively higher radiation dose and time consumption. METHODS: The purpose of this study was to evaluate the potential of summed image that obtained from parenchymal phase of the dynamic technetium-99m-N,N-ethylenedicysteine (Tc-99m EC) scintigraphy in the detection of renal parenchymal defects and in the estimation of DRF, and to compare the results of this method with those of Tc-99m DMSA scintigraphy. The uptake ratios of the kidney to body background were also calculated for these two methods. Twenty-nine children with various renal disorders underwent both static Tc-99m DMSA and dynamic Tc-99m EC scintigraphy. The cortical analysis of Tc-99m EC scintigraphy was performed on the summed image obtained from dynamic images using the time interval between the first 45-120 sec. RESULTS: There was a very close correlation between these two methods with respect to DRF (r = 0.99). In the detection of renal parenchymal lesions, scintigraphy with Tc-99m DMSA detected more lesions, and the sensitivity and specificity of the summed Tc-99m EC images were calculated as 92.6% and 100%, respectively. In addition, the ratios of mean uptake values for Tc-99m DMSA and Tc-99m EC images were 7.59 +/- 2.17 and 2.95 +/- 0.91, respectively. This ratio of Tc-99m EC seems to be acceptable and allows good delineation of the kidneys. But, the main disadvantages of the summed Tc-99m EC images in comparison with static Tc-99m DMSA images are the use of only posterior projection that may be an important drawback in patients with abnormal kidney positions, lower image counts and higher pixel size because of dynamic acquisition. CONCLUSION: These results show that summed Tc-99m EC images with an acceptable high image contrast provide an accurate DRF calculation in patients without abnormal kidney positions and allow the detection of most renal parenchymal abnormalities. However, Tc-99m DMSA scintigraphy remains the gold standard method because of its well known advantages.     

99Tc(m)(V)DMSA scintigraphy in skeletal metastases and superscans arising from various malignancies: diagnosis, treatment monitoring and therapeutic implications

Skeletal metastases arising from a wide variety of malignancies including a few cases with superscan appearance were evaluated using (99)Tc(m) MDP bone scanning and (99)Tc(m)(V)DMSA scintigraphy. Whole body planar scans were obtained at 3 h and 24 h after injection of 740 MBq (99)Tc(m) MDP and 5 days later at similar times after injection of 555 MBq of (99)Tc(m)(V)DMSA. A qualitative as well as quantitative comparison was made between the (99)Tc(m) MDP bone scan and the (99)Tc(m)(V)DMSA scan in detection of osseous metastases. The reference methods used for discordant or equivocal lesions were correlative morphological imaging modalities, for example additional conventional radiography, CT or MRI. The present pictorial review deals with the results of qualitative analysis of the study. A total of 75 cases have been evaluated. The vignettes illustrated in the present article demonstrate avid (99)Tc(m)(V)DMSA concentration in skeletal metastases from a wide variety of malignancies and thus expand the potential therapeutic indications for 188/186 Re(V)DMSA. The study also demonstrates the valuable supporting role a (99)Tc(m)(V)DMSA scan can play in the confirmation as well as evaluation of the extent of malignant infiltration in a suspected superscan in routine skeletal scintigraphy. In addition, a (99)Tc(m)(V)DMSA scan detected a number of metastatic lesions in and around joints and regions with previous surgical intervention that were inconclusive in the bone scan. The results in a few patients who were available for repeat scintigraphy following treatment, support the convincing evidence that (99)Tc(m)(V)DMSA accumulation may be a sensitive indicator of patient response to therapy. This might have an important bearing in the context of increasing "cold" bisphosphonate usage in the treatment of skeletal metastases, where skeletal scintigraphy with a radiolabelled bisphosphonate derivative can often be fallacious because of competitive inhibition by the non-labelled form.     

Differential renal function using technetium-99m dimercaptosuccinic acid (DMSA): in vitro correlation.

The relationship between differential renal uptake of Tc-99m 2-3 dimercaptosuccinic acid (DMSA) and differential renal function was examined in normal and abnormal dogs by correlating Tc-99m DMSA localization with relative renal blood flow and creatining clearance. There was close correlation of fractional Tc-99m DMSA localization with relative renal function.     

Evaluation of Tc-99m(V) DMSA for imaging inflammatory lesions: An experimental study

The present study evaluated^99mTc(V) DMSA as an agent for the visualization of inflammatory lesions in comparison to^99mTc(HI) DMSA and^99mTc-HIG. All three radiopharmaceuticals were prepared with commercial kits.^99mTc(V) DMSA was prepared at neutral pH by the addition of first bicarbonate and then pertechnetate to the kit contents. The labeling efficiency was 99% as determined by ITLC. Abscesses were induced by i.m. injection of 50 μl turpentine into the right thighs of 36 Swiss albino mice. Six days later 3.7 MBq of each radiopharmaceutical was i.v. administered to 12 mice. The mice were sacrificed at 1,3,6 and 24 h later. Scintigrams were obtained with a gamma camera. The abscesses were better visualized on scintigrams with^99mTc(V) DMSA compared to^99mTc(III) DMSA, starting at 1 h. The animals were dissected and the organs were removed, weighed and the radioactivity determined with a gamma counter. The abscess to other tissue ratios were higher with^99mTc(V) DMSA than the other radiopharmaceuticals. The max. abscess/muscle ratios were 9.46 ± 3.20 (24 h), 4.19 ± 1.39 (6 h) and 5.98 ± 1.17 (24 h) and max. abscess/blood ratios were 6.22 ± 1.41, 4.09 ± 0.84 and 0.914 ± 0.351 all at 24 h for^99mTc(V) DMSA,^99mTc(III) DMSA and^99mTc-HIG, respectively. Experimental arthritis was produced in 6 New Zealand white rabbits by intra-articular injection of ovalbumin. Four days later 37 MBq of^99mTc(V) DMSA and^99mTc-HIG were each i.v. administered to 3 rabbits. Scintigrams obtained at 1, 3, 6, and 24 h clearly demonstrated arthritic joints. ROFs over arthritic joints were compared to contralateral normal joints (A/C). The max. A/C ratios were 2.10 ± 0.31 (3 h) and 2.92 ± 0.99 (24 h) for^99mTc(V) DMSA and^99mTc-HIG, respectively. Our results indicated the feasibility of imaging inflammatory lesions with^99mTc(V) DMSA.     

False-positive technetium-99m DMSA renal imaging in two cases of malrotated kidney

Technetium-99m dimercaptosuccinic acid (Tc-99m DMSA) has been used as a renal imaging agent of choice. A few false-positive cases of Tc-99m DMSA imaging have been reported. The authors have experienced false-positive Tc-99m DMSA imagings in two cases of a malrotated kidney, and this finding previously has not been reported in the literature. The possibility of its nuclear imaging diagnosis with Tc-99m DTPA is also discussed.