Comparison of absolute renal uptake by using Tc-99m MAG-3 and Tc-99m DMSA.

PURPOSE: The purpose of this study is to compare the value of absolute renal uptake (ARU %) in patients by using Tc-99m MAG-3 and Tc-99m DMSA scan. MATERIAL AND METHODS: Absolute renal uptake is calculated using Tc-99m MAG-3 and Tc-99m DMSA in renal scintigraphy, Itoh and Tauex kidney depth methods used, respectively. n = 40 adult patients of both genders were included. All patients underwent Tc-99m MAG-3 and Tc-99m DMSA, respectively. RESULTS: The values of ARU (%) were calculated separately in selected patients n = 40, (left = 17, right = 23 normal functioning kidneys) by MAG-3 and DMSA. Absolute renal uptake (%) of Tc-99m MAG-3 in left kidneys was found to be 15.2 ±â€…3.4, with spilt renal function 79.2 ±â€…14.7 and ARU (%) in right kidneys 16.2 ±â€…3.4 with spilt renal function 77.5 ±â€…19. Absolute renal uptake of Tc-99m DMSA in left kidneys was 17.5 ±â€…3.2 and in right kidneys 17.9 ±â€…4.5 with spilt renal function 81.8 ±â€…10.7 and 79.3 ±â€…13.8 for left and right kidney, respectively. Statistical analysis showed strong Pearson correlation. CONCLUSION: Absolute renal uptake % was found to be more reliable in cases of bilateral compromised kidneys. ARU (%) calculated by Tc-99m MAG-3 solely can be used as predictor of renal function. The use of Tc-99m MAG-3 has more advantages than Tc-99m DMSA alone in renal scintigraphy as dynamic scintigraphy gives less radiation burden to patient, more information regarding renal function, and shorter stay time at hospital in comparison to static renal imaging. SRF % is less reliable than ARU (%).

Assessment of drug transporters involved in the urinary secretion of [99mTc]dimercaptosuccinic acid.

INTRODUCTION: We clarified the renal uptake and urinary secretion mechanism of [99mTc]dimercaptosuccinic acid ([99mTc]DMSA) via drug transporters in renal proximal tubules. METHODS: [99mTc]DMSA was added to human embryonic kidney 293 cells expressing human multidrug and toxin extrusion (MATE)1 and MATE2-K, carnitine/organic cation transporter (OCTN)1 and OCTN2, and organic cation transporter (OCT)2; to Flp293 cells expressing human organic anion transporter (OAT)1 and OAT3; and to vesicles expressing P-glycoprotein (P-gp), multidrug resistance associated protein (MRP)2, MRP4, or breast cancer resistance protein with and without probenecid (OAT inhibitor for both OATs and MRPs). Time activity curves of [99mTc]DMSA with and without probenecid were established using LLC-PK1 cells. Biodistribution and single photon emission computed tomography (SPECT) imaging in mice were conducted using [99mTc]DMSA with and without probenecid. RESULTS: [99mTc]DMSA uptake was significantly higher in Flp293/OAT3 than in mock cells. Uptake via OAT3 was inhibited by probenecid. [99mTc]DMSA uptake into vesicles that highly expressed MRP2 was significantly higher in adenosine triphosphate (ATP) than in adenosine monophosphate (AMP), and probenecid decreased uptake to similar levels as that in AMP. In the time activity curves for [99mTc]DMSA in LLC-PK1 cells, probenecid loading inhibited accumulation from the basolateral side into LLC-PK1 cells, whereas accumulation from the apical side into cells gradually increased. Transport of [99mTc]DMSA from both sides was low. Biodistribution and SPECT imaging studies showed that [99mTc]DMSA with probenecid loading resulted in significantly higher accumulation in blood, heart, liver, and bladder after [99mTc]DMSA injection compared with control mice. Probenecid induced significantly lower accumulation in the kidney after [99mTc]DMSA injection. CONCLUSIONS: [99mTc]DMSA accumulates in renal proximal tubular epithelial cells from blood via OAT3 on the basolateral side, and then a small volume of [99mTc]DMSA will be excreted in urine via MRP2. ADVANCES IN KNOWLEDGE: [99mTc]DMSA accumulates via OAT3 in renal proximal tubular epithelial cells and is slightly excreted from the cells via MRP2. IMPLICATIONS FOR PATIENT CARE: [99mTc]DMSA may be useful for measuring renal transport function with OAT3 in patients.

RADIOISOTOPE DIAGNOSTIC ALGORITHM FOR THE RELAPSE AND METASTASES DETECTION IN THE IODINE-NEGATIVE DIFFERENTIATED THYROID CANCER. / RADIONUKLIDNYI DIAGNOSTYChNYI ALGORYTM DLIa VYIaVLENNIa RETsYDYVIV I METASTAZIV U KhVORYKh Z IOD-NEGATYVNYMY FORMAMY DYFERENTsIIOVANOGO RAKU ShchYTOPODIBNOÏ ZALOZY.

OBJECTIVE: Developing of algorithm for the post-surgical management of patients with iodine-negative metastasesof differentiated thyroid cancer (DTC). MATERIALS AND METHODS: The DTC patients with iodine-negative metastases (n = 115) were enrolled in the study.Of them the whole body scintigraphy (WBS) was performed with technetium-99m-hexakis-2-methoxyisobutylisonitrile(99mTc-MIBI) (n = 30), WBS with technetium-99m dimercaptosuccinic acid (99mTc-DMSA) (n = 30), 18FDG PET (n = 30), andcomputer tomography (CT-scan) (n = 25). Complex 99mTc-pertechnetate scans including the dynamic and static scintigraphy was performed supplementary to 99mTc-MIBI WBS in 10 patients to obtain the angiographic curves from DTCmetastatic foci. The non-radioiodine radiopharmaceutical technologies, namely the labeled 99mTc-MIBI, 99mTc-DMSA, 99mTc-pertechnetate, and 18FDG were applied to detect the iodine-negative DTC metastases. Radioisotopic examinationswere performed at the dual-head gamma camera (Mediso Medical Imaging Systems Ltd., Hungary) and single photonemission computed tomography (SPECT) scanner «E.CAM¼ (Siemens, Germany). PET/CT scans were performed on the«Biograph 64 TruePoint¼ imaging platform (Siemens, Germany) in accordance with the European Association of NuclearMedicine (EANM) recommendations for the Siemens imaging devices with 3D-mode data acquisition. RESULTS: The conducted research suggested that it is feasible to use the non-radioiodine (99mTc-MIBI and 99mTc-DMSA)radiopharmaceutical technologies to detect the iodine-negative DTC metastases. 18FDG PET is a highly informativetechnology for the detection of iodine-negative DTC metastases in case of lung involvement in the process. Compareof the non-radioiodine radiopharmaceuticals, CT scan and 18FDG-PET/CT indicated the highest sensitivity of 18FDGPET/CT (p < 0.05). WBS with 99mTc-MIBI and 99mTc-DMSA featured the highest specificity (100 %, p < 0.05). X-ray CTis marked by the significantly lower either sensitivity, specificity, and accuracy rate (p > 0.05). Developing andapplication of algorithm for the post-surgical management of patients with iodine-negative forms of DTC will allowfor the betimes detection of relapses and metastases with administration of adequate surgical, radiation, and targeted treatment. CONCLUSIONS: Obtained results offer the opportunity to optimize the post-surgical management of patients withiodine-negative DTC forms using the options of radionuclide diagnostics with non-radioiodine radiopharmaceuticals. The latter are readily available providing the cost-cutting of diagnostic support in these patients. Place ofmorphological methods of diagnosis is determined and stage of monitoring of patients with the iodine-negativemetastases is established. Possibility of the 18FDG-PET tests for the early diagnosis of iodine-negative metastases inDTC for the first time have been studied and substantiated in Ukraine. A comprehensive radiation algorithm for thelong-term monitoring of this category of patients will allow the timely detection of recurrences and metastases ofDTC and appropriate surgery, radiation and targeted therapy administration. Data obtained as a result of the studyallowed to improve the overall and recurrence-free survival rates in the able-bodied DTC patients and reduce thecosts of follow-up of patients with iodine-negative forms of DTC.

The Screening of Renoprotective Agents by 99mTc-DMSA: A Review of Preclinical Studies.

BACKGROUND: Nephrotoxicity is a prevalent consequence of cancer treatment using radiotherapy and chemotherapy or their combination. There are two methods; histological and biochemical, to assess the kidney damage caused by toxic agents in animal studies. Although these methods are used for the try-out of renoprotective factors, these methods are invasive and time-consuming, and also, lack the necessary sensitivity for primary diagnosis. Quantitative renal 99mTc-DMSA scintigraphy is a noninvasive, precise and sensitive radionuclide technique which is used to assess the extent of kidney damage, so that the extent of injury to the kidney will be indicated by the renal uptake rate of 99mTc-DMSA in the kidney. In addition, this scintigraphy evaluates the effect of the toxic agents by quantifying the alterations in the biodistribution of the radiopharmaceutical. CONCLUSION: In this review, the recent findings about the renoprotective agents were evaluated and screened with respect to the use of 99mTc-DMSA , which is preclinically and clinically used for animal cases and cancer patients under the treatment by radiotherapy and chemotherapy.

Functional Evaluation of an Ectopic Supernumerary Kidney in Pelvis.

BACKGROUND: Supernumerary kidney is an accessory organ with its own encapsulated parenchyma, blood vessels and ureters, either separated from the normal kidney or connected to it via fibrous tissue and ectopic kidney is a migration abnormality of the kidney. Here, we have evaluated a rare case of the supernumerary and ectopic kidney with DMSA, MAG3 and also CT fusion of the images. METHODS: The absolute divided renal function was calculated for each kidney by DMSA. The MAG3 scintigraphy showed no obstruction in the ureteropelvic junction. Furthermore, the renogram curve and Tmax and time to ½ values were assessed. Two months after the conventional scintigraphies, the patient was referred to a CT scan and the fusion of DMSA SPECT and CT data was generated on a workstation. RESULTS: The ectopic supernumerary kidney was functioning very well except a small hypoactive area, visible on DMSA, which was possibly a minimal pelvicalyceal dilatation. However, consequent CT scan did not show any pathology. CONCLUSION: It is important to evaluate particularly complicated or rare cases with multimodality systems with 3D or fusion techniques for the accurate diagnosis.

Activity estimation and biokinetic analysis of 99mTc-DMSA in renal infant patients using a gamma camera.

Biokinetic data from the administration of radiopharmaceuticals is essential in nuclear medicine dosimetry. It has particular significance in children, as their metabolism is very different from adults. Biokinetic models for paediatric patients could therefore need to be adapted to better reflect their absorption, retention and excretion functions, when compared to adults. Obtaining quality in vivo infant or paediatric biokinetic data is then essential to improve the available reference models, which in turn can lead to the optimization of paediatric procedures and protocols in clinical practice. This study analyses the biokinetic behaviour of 99mTc-dimercaptosuccinic acid (DMSA), in 8 infants aged 4 months to 2 years old, through an imaging study using a gamma camera, and compares the obtained values with those obtained with the reference ICRP biokinetic model. The in vivo data was treated using an adapted methodology from the MIRD 16 pamphlet. Activity curves for the liver, the kidney and the whole body, were built, and new effective absorption, retention and excretion half-lives were estimated, and compared with the reference biokinetic parameters of ICRP 128. The obtained residence time in the kidneys of 2.56 h, has a deviation of 30.8% to the ICRP 128 value of 3.70 h. The obtained maximum uptake in the kidneys was of 0.22/A0, which compares to the value of 0.31/A0 for ICRP. The obtained biokinetic parameters were used to estimate the absorbed dose. The obtained dose values are smaller than the reference ICRP 128 ones by 32.1% in the kidneys, and 18.4% in the liver.

Dosimetry of 99mTc (DTPA, DMSA and MAG3) used in renal function studies of newborns and children.

The dose to kidneys of newborns and 1-year old children was calculated using the MIRD methodology. In order to perform renal studies radiopharmaceutical like 99mTc-DTPA, 99m Tc-MAG3 and 99mTc-DMSA are used. Here, besides the anatomic and structure information of kidneys another data are provided in benefit of patient, however during the radioisotope decay emitted radiations delivers, totally or partially, their energy. Therefore is important to estimate the internal radiation dose of the organs. The largest dose to kidneys comes from the self-dose and it is due to the charged particles emitted during 99mTc decay. From the three radiopharmaceutical here used the largest dose to kidneys is due to 99mTc-DMSA, and the smaller dose is due to 99mTc-MAG3.

99mTc-DMSA Uptake in a Sister Mary Joseph's Nodule From Ovarian Cancer.

A 50-year-old woman with ovarian cancer underwent Tc-DMSA scan to evaluate the functional status of the right hydronephrotic kidney. The images incidentally revealed a well-defined focus of mild radiotracer uptake at the midanterior abdominal wall, which correlated with a metastatic Sister Mary Joseph's nodule seen on CT performed a week earlier.

Influence of Annona muricata (soursop) on biodistribution of radiopharmaceuticals in rats.

PURPOSE: To evaluate the effect of hydroalcoholic extract of A. muricata on biodistribution of two radiopharmaceuticals: sodium phytate and dimercaptosuccinic acid (DMSA), both labeled with 99mtechnetium. METHODS: Twenty four Wistar rats were divided into two treated groups and two controls groups. The controls received water and the treated received 25mg/kg/day of A. muricata by gavage for ten days. One hour after the last dose, the first treated group received 99mTc-DMSA and the second sodium 99mTc-phytate (0.66MBq each group), both via orbital plexus. Controls followed the same protocol. Forty min later, all groups were sacrificed and the blood, kidney and bladder were isolated from the first treated group and the blood, spleen and liver isolated from the second treated group. The percentage of radioactivity per gram of tissue (%ATI/g) was calculated using a gamma counter. RESULTS: The statistical analysis showed that there was a statistically significant decrease (p<0.05) in the uptake of %ATI/g in bladder (0.11±0.01and1.60±0.08), kidney (3.52±0.51and11.84±1.57) and blood (0.15±0.01and 0.54±0.05) between the treated group and control group, respectively. CONCLUSION: The A. muricata hydroalcoholic extract negatively influenced the uptake of 99mTc-DMSA in bladder, kidney and blood of rats.

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.

Monitoring of renal function using 99mTc-DMSA and 99mTc-DTPA scintigraphy in patients with spinal cord injury.

AIM: The aim of this study was to assess the degree of alterations of renal function by using 99m-technetium dimercaptosuccinic acid ((99m)Tc-DMSA) and 99m-technetium diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) scintigraphy in spinal cord injury (SCI) patients. MATERIAL AND METHODS: Twenty-two consecutive SCI (15 paraplegic and 7 tetraplegic) patients (mean age: 49.1±13.4 years) who had no urinary symptoms participated in this prospective study. The mean duration of injury was 45.6±48.8 months before. Sixteen patients had at least one urinary tract infection history. Renal cortical scintigraphy with (99m)Tc-DMSA, radionuclide renography with (99m)Tc-DTPA and renal ultrasound were performed within 2-week period. RESULTS: Four (18%) patients had serious pathology on their kidneys such as unilateral or bilateral parenchymal scarring and increased background uptake in their renal cortical scintigraphy with (99m)Tc-DMSA. Two of them had grade 3-4 pelvicaliceal ectasia on ultrasound. Additionally, 2 of 18 remaining patients had grade 2 pelvicaliceal ectasia on ultrasound. Sixteen (73%) patients had markedly delayed or delayed and decreased functions of one or both of kidneys on radionuclide renography. However, only four patients had grade 2-4 pelvicaliceal ectasia and none of them had a finding of loosening of renal parenchyma. CONCLUSION: Combined use of renal cortical scintigraphy and radionuclide renography appears to be contributive to renal ultrasound in the long-term follow-up of patients with SCI. Patients with abnormal findings should be closely followed, and early therapeutic interventions may enable lower morbidity and mortality rates in these patients.

An approach for balancing diagnostic image quality with cancer risk: application to pediatric diagnostic imaging of 99mTc-dimercaptosuccinic acid.

UNLABELLED: A recent survey of pediatric hospitals showed a large variability in the activity administered for diagnostic nuclear medicine imaging of children. Imaging guidelines, especially for pediatric patients, must balance the risks associated with radiation exposure with the need to obtain the high-quality images necessary to derive the benefits of an accurate clinical diagnosis. METHODS: Pharmacokinetic modeling and a pediatric series of nonuniform rational B-spline-based phantoms have been used to simulate (99m)Tc-dimercaptosuccinic acid SPECT images. Images were generated for several different administered activities and for several lesions with different target-to-background activity concentration ratios; the phantoms were also used to calculate organ S values for (99m)Tc. Channelized Hotelling observer methodology was used in a receiver-operating-characteristic analysis of the diagnostic quality of images with different modeled administered activities (i.e., count densities) for anthropomorphic reference phantoms representing two 10-y-old girls with equal weights but different body morphometry. S value-based dosimetry was used to calculate the mean organ-absorbed doses to the 2 pediatric patients. Using BEIR VII age- and sex-specific risk factors, we converted absorbed doses to excess risk of cancer incidence and used them to directly assess the risk of the procedure. RESULTS: Combined, these data provided information about the tradeoff between cancer risk and diagnostic image quality for 2 phantoms having the same weight but different body morphometry. The tradeoff was different for the 2 phantoms, illustrating that weight alone may not be sufficient for optimally scaling administered activity in pediatric patients. CONCLUSION: The study illustrates implementation of a rigorous approach for balancing the benefits of adequate image quality against the radiation risks and also demonstrates that weight-based adjustment to the administered activity is suboptimal. Extension of this methodology to other radiopharmaceuticals would yield the data required to generate objective and well-founded administered activity guidelines for pediatric and other patients.

Study on 99mTc-MAG3 and 99mTc-DMSA renal accumulation using in vitro cellular model.

Mercaptoacetyltriglycine (MAG3) and dimercaptosuccinic acid (DMSA) labelled with technetium-99m belongs to standard renal radiodiagnostics. However, the renal transport mechanisms responsible for their high renal uptake have not been fully explained. In addition, no in vitro experimental study comparing the renal uptake of these radiopharmaceuticals at the cellular level has not been performed. The investigation compared the 99mTc-MAG3 and 99mTc-DMSA renal uptake using primary rat renal cells and evaluated contribution of active and passive transport processes to the renal accumulation. The renal cells were isolated from the rat kidneys by means of the two-phase collagenase perfusion method. The used experimental model showed to be useful tool for such type of investigation. The results documented significant quantitative and qualitative differences in the accumulation of 99mTc-DMSA and 99mTc-MAG3 in the rat isolated cells. The found experimental data indicated several times higher uptake of 99mTc-MAG3 than that found in 99mTc-DMSA. 99mTc-MAG3 cellular uptake was substantially decreased when active, energy-dependent processes were inhibited. However, 99mTc-DMSA accumulation in the renal cells demonstrated only a minor dependency on energy. These findings demonstrate a very different character of the membrane transport determining 99mTc-DMSA and 99mTc-MAG3 renal accumulation.

Increased breast density correlates with the proliferation-seeking radiotracer (99m)Tc(V)-DMSA uptake in florid epithelial hyperplasia and in mixed ductal carcinoma in situ with invasive ductal carcinoma but not in pure invasive ductal carcinoma or in mild epithelial hyperplasia.

The purpose of this study was to assess the relationship of mammographic breast density (BD) and cell proliferation/focal adhesion kinase activation-seeking radiotracer technetium 99m pentavalent dimercaptosuccinic acid (99mTc(V)-DMSA) uptake in women with different breast histologies, that is, mild epithelial hyperplasia (MEH), florid epithelial hyperplasia (FEH), mixed ductal carcinoma in situ with invasive ductal carcinoma (DCIS + IDC), and pure IDC. Fifty-five women with histologically confirmed mammary pathologies were submitted preoperatively to mammography and 99mTc(V)-DMSA scintimammography. The percentage and intensity of 99mTc(V)-DMSA uptake and the percentage of BD were calculated by computer-assisted methods and compared (t-test) between the breast pathologies. In breasts with increased BD, FEH and DCIS + IDC were found. On the contrary, pure IDC and MEH were identified in breasts with significantly lower BD values. In breasts with increased 99mTc(V)-DMSA area and intensity of uptake, FEH was the main lesion found compared to all other histologies. Linear regression analysis between BD and 99mTc(V)-DMSA uptake area and intensity revealed significant coefficients of correlation (r  =  .689, p < .001 and r  =  .582, p < .001, respectively). Increased BD correlates with the presence of FEH and mixed DCIS + IDC but not with pure IDC or MEH. Its close relationship to 99mTc(V)-DMSA, which also showed an affinity to FEH, indicates that stromal microenvironment may constitute a specific substrate leading to progression to different subtypes of cancerous lesions originating from different pathways.

Novel techniques and newer markers for the evaluation of "proximal tubular dysfunction".

Renal Fanconi syndromes are both clinically challenging and physiologically fascinating. The diagnosis requires a certain index of suspicion to correctly identify the clinical symptomatology and pursue the appropriate laboratory evaluations. The renal Fanconi syndrome (FS) is a defect of proximal tubular function attributable to different rare inherited diseases or acquired disorders caused by a multitude of exogenous agents. It can manifest as complete or incomplete FS, characterized by low molecular weight proteinuria, glucosuria, aminoaciduria, and loss of electrolytes, bicarbonate and lactate. Implementation of new methods and recent findings from urinary proteome pattern in patients with renal FS has led to the identification of new markers for proximal tubular dysfunction. Future combined proteomic and metabonomic studies will provide additional potential biomarkers and may help to gain novel insights in the diagnosis and differentiation of the various forms of FS. Moreover, the observation of poor renal uptake of 99 mTc-DMSA in patients with tubular proteinuria, which is not fully understood yet, may also help to elucidate the individual basis of FS in early stages. This review focuses on the new advances in the evaluation of proximal tubular dysfunction in various forms of Fanconi syndrome.

(99m)Tc-DMSA absolute and relative renal uptake in cats: procedure and normal values.

In this study we investigated the influence of technical factors (positioning, background (BG) correction and attenuation correction) on qualitative and quantitative (absolute (AU) and relative (RU) uptake) assessment of feline kidneys with (99m)technetium labelled dimercaptosuccinic acid ((99m)Tc-DMSA). Eleven healthy adult cats were included. Influence of BG and depth correction on quantitative assessment was evaluated. Depth correction was based on the geometric mean method (using dorsal and ventral images) and the use of two standards placed over each individual kidney. Visual evaluation showed superiority of dorsal and ventral over lateral positioning due to increased separation of the kidneys permitting region of interest (ROI) placement without overlap. No apparent influence of BG correction was found for RU. However, AU was systematically overestimated without BG correction. Depth correction did not seem to affect RU in most cases, however, in some cats the differences were not negligible. The values for AU without depth correction were lower compared to depth corrected values.