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.

Real-Time DMSA-SPECT/US Fusion Imaging Revealing Nonscarring Loss of Function After Pyelonephritis.

Using real-time SPECT/US fusion imaging, the localization of an uptake defect in DMSA scan could be identified unambiguously after being uncertain in ultrasound alone. Thereby, a localized functional loss, due to history of pyelonephritis, without scarring, but reduced cortical thickness could be verified. DMSA-SPECT/US primarily demonstrates its utility in depiction of renal pathologies and may be a descriptive tool in equivocal constellation of findings.

A Pediatric Case of Well-Functioning Supernumerary Kidney: Relative Renal Function Assessment Using Radionuclide Imaging.

We present an interesting image of a well-functioning supernumerary kidney evaluated with DMSA (dimercaptosuccinic acid) renal scintigraphy in a 14-year-old girl. At 2 years of age, the patient had a diagnosis of supernumerary kidney. She remained asymptomatic up to childhood age, and then a DMSA study was required to guide the following adequate surveillance strategy. DMSA study provided a clear imaging of supernumerary kidney in the left side of the abdomen showing a regular uptake and a normal function in relation to its own size.

Folate receptor-targeted radionuclide therapy: preclinical investigation of anti-tumor effects and potential radionephropathy.

INTRODUCTION: Application of therapeutic folate radioconjugates is a promising option for the treatment of folate receptor (FR)-positive tumors, although high uptake of radiofolates in the kidneys remains a critical issue. Recently, it was shown that enhancing the blood circulation of radiofolates results in increased tumor uptake and reduced retention of radioactivity in the kidneys. In this study, we investigated and compared the anti-tumor effects and potential long-term damage to the kidneys after application of an albumin-binding ((177)Lu-cm09), and a conventional ((177)Lu-EC0800) folate radioconjugate. METHODS: In vivo studies were performed with KB tumor-bearing nude mice. (177)Lu-EC0800 and (177)Lu-cm09 were applied at variable quantities (10-30 MBq/mouse), and the tumor growth was monitored over time. Mice without tumors were injected with the same radiofolates and investigated over eight months by determination of creatinine and blood urea nitrogen plasma levels and by measuring renal uptake of (99m)Tc-DMSA using SPECT. At the study end, the morphological changes were examined on renal tissue sections using variable staining methods. RESULTS: Compared to untreated controls, dose-dependent tumor growth inhibition and prolonged survival was observed in all treated mice. In line with the resulting absorbed dose, the treatment was more effective with (177)Lu-cm09 than with (177)Lu-EC0800, enabling complete tumor remission after application of ≥20MBq (≥28Gy). Application of radiofolates with an absorbed renal dose ≥23 Gy showed increased levels of renal plasma parameters and reduced renal uptake of (99m)Tc-DSMA. Morphological changes observed on tissue sections confirmed radionephropathy of variable stages. CONCLUSIONS: (177)Lu-cm09 showed more favorable anti-tumor effects and significantly less damage to the kidneys compared to (177)Lu-EC0800 as was expected based on improved tumor-to-kidney ratios. It was demonstrated that enhancing the blood circulation time of radiofolates was favorable regarding the risk-benefit profile of a therapeutic application. These results hold promise for future translation of the albumin-binder concept to the clinics, potentially enabling FR-targeted radionuclide therapy in patients.

Both a visual and a semiquantitative analysis for differentiating benign from malignant chondrogenic bone tumors using Tc-99m (V) DMSA scintigraphy: a prospective study.

OBJECTIVE: The aims of this prospective study were to assess the relationship between tumor aggressiveness and Tc-99m (V) dimercaptosuccinic acid (DMSA) uptake in chondrogenic bone tumors and the value of Tc-99m (V) DMSA scintigraphy for differentiating benign from malignant tumors. METHODS: Twenty-four patients with chondrogenic tumors (19 benign and five malignant) underwent Tc-99m DMSA (V) scintigraphy. Radiopharmaceutical uptake was classified using a three-point scale to allow a visual-only analysis, and a tumor-to-background contrast (TBC) was computed using regions of interest to provide a semiquantitative analysis. Spearman's correlation coefficient was used to assess the correlation between tumor aggressiveness and TBC. The difference in TBC between benign and malignant tumors was analyzed with the Mann-Whitney U-test. An appropriate cutoff value of TBC was chosen for the diagnosis of malignancy of a tumor using receiver operating characteristic analysis. RESULTS: Six benign tumors showed negative uptake (uptake score 0), whereas 13 benign tumors showed positive uptake (n=10 uptake score 1; n=3 uptake score 2). All chondrosarcomas showed positive uptake (n=2 uptake score 1; n=3 uptake score 2). A significant correlation was found between tumor aggressiveness and TBC. A significant difference was seen in TBC between benign and malignant tumors. With the chosen cutoff value of TBC equal to 0.611, the sensitivity was 80.0%, specificity was 78.9%, the positive predictive value was 50.0%, and the negative predictive value was 93.8%. CONCLUSION: Tc-99m (V) DMSA scintigraphy may have the potential to improve diagnostic methods for detecting chondrosarcomas using visual and/or semiquantitative analyses.

Vitamin E as adjuvant treatment for urinary tract infection in girls with acute pyelonephritis.

INTRODUCTION: Vitamin E is a fat-soluble vitamin that functions as an antioxidant. The aim of this study was to investigate the effects of vitamins E supplementation in combination with antibiotics for the treatment of girls with acute pyelonephritis. MATERIALS AND METHODS: This double-blinded randomized controlled trial was conducted on 152 girls aged 5 to 12 years with a first acute pyelonephritis episode based on technetium Tc 99m dimercaptosuccinic acid (99mTc-DMSA). They were randomized to receive a 14-day treatment with only antibiotics (control group; n = 76) and 14-day treatment with supplements of vitamin E (intervention group; n = 76) in addition to the antibiotics. Patients' clinical symptoms were monitored for 14 days and urine culture was performed 3 to 4 days and 7 to 10 days after the start of the treatment and its completion, respectively. All of the girls once underwent DMSA scan 4 to 6 months after the treatment. RESULTS: During the follow-up days, the mean frequency of fever (P = .01), urinary frequency (P = .001), urgency (P = .003), dribbling (P = .001), and urinary incontinence (P = .006) were significantly lower in the intervention group compared to the control group. There was no significant difference in the results of urine culture 3 to 4 days after the start of treatment (P = .16) and 7 to 10 days after its termination (P = .37). There was also no significant difference between the results of DMSA scan 4 to 6 months after the start of treatment (P = .31). CONCLUSIONS: Vitamin E supplementation has a significant effect in ameliorating sign and symptoms of UTI. However, further studies are recommended to confirm these findings.

Abnormal focal 99mTc-DMSA uptake in the lung--report of two cases.

Extrarenal uptake of 99mTc-DMSA is a rare finding, which has been described in some unusual conditions as bone metastasis, aortic aneurysm and hemangioma. The purpose of this report is to present two cases of abnormal 99mTc-DMSA uptake in the lungs, which remained unexplained even after radiologic assessment.

Assessment of tracer 99mTc(V)-DMSA uptake as a measure of tumor cell proliferation in vitro.

PURPOSE: To examine whether (99m)Tc(V)-DMSA could be used as a non-invasive measure of cancer cell proliferation. METHODS: Human breast cancer MCF-7, MDA-MB-231 and pII, and prostate cancer PC-3 cell lines were grown to 30, 50 and 100% confluency and pulsed with (99m)Tc(V)-DMSA in media for 60 min at 37°C. DNA synthesis was analysed by quantification of the S phase using flow cytometry, [methyl-(3)H]thymidine incorporation and expression of proliferation markers PCNA and Ki-67 using realtime PCR. One way ANOVA was used to compare groups. RESULTS: In all cell lines rates of (99m)Tc(V)-DMSA uptake were inversely related to cell density. This was paralleled by similar trends in S phase proportions, [methyl-(3)H]thymidine incorporation and expression of PCNA and Ki-67. CONCLUSION: Rates of (99m)Tc(V)-DMSA uptake into different types of tumour cells correlate well with cell density that is useful as a non-invasive measure of tumour cellular proliferation in vivo.

Renal uptake of 99mTc-dimercaptosuccinic acid is dependent on normal proximal tubule receptor-mediated endocytosis.

UNLABELLED: (99m)Tc-labeled dimercaptosuccinic acid ((99m)Tc-DMSA) accumulates in the kidney cortex and is widely used for imaging of the renal parenchyma. Despite its extensive clinical use, the mechanism for renal targeting of the tracer is unresolved. Megalin and cubilin are cooperating receptors essential to the proximal tubule endocytic uptake of proteins from the glomerular ultrafiltrate. We have used megalin/cubilin-deficient mice produced by gene knockout to determine whether receptor-mediated endocytosis is responsible for the renal uptake of (99m)Tc-DMSA. METHODS: Control or megalin/cubilin-deficient mice were injected intravenously with 0.5 MBq of (99m)Tc-DMSA or (99m)Tc-mercaptoacetyltriglycine (MAG3). Whole-body scintigrams and the activity in plasma, urine, and the kidneys were examined 6 h after injection. The size and identity of (99m)Tc-DMSA-bound proteins in urine were analyzed by fractionation by centrifugation and separation by sodium dodecyl sulfate polyacrylamide gel electrophoresis, followed by autoradiography and mass spectrometry. RESULTS: No renal accumulation of (99m)Tc-DMSA was identified in scintigrams of megalin/cubilin-deficient mice. The renal accumulated activity of the tracer was reduced to 11.4% (± 2.5%, n = 7) of the normal uptake in control mice, correlating with a reduction in renal megalin/cubilin expression in knockout mice to about 10% of normal. The reduced renal uptake in megalin/cubilin-deficient mice was accompanied by an increase in the urinary excretion of (99m)Tc-DMSA. Size separation of the urine by ultracentrifugation and sodium dodecyl sulfate polyacrylamide gel electrophoresis demonstrated that in megalin/cubilin-deficient mice an increased amount of (99m)Tc-DMSA was excreted in an approximately 27-kDa form, which by mass spectrometry was identified as the plasma protein α1-microglobulin, an established megalin/cubilin ligand. CONCLUSION: (99m)Tc-DMSA is filtered bound to α1-microglobulin and accumulates in the kidneys by megalin/cubilin-mediated endocytosis of the (99m)Tc-DMSA protein complex. Renal accumulation of (99m)Tc-DMSA is thus critically dependent on megalin/cubilin receptor function and therefore is a marker of proximal tubule endocytic activity.

Detección mediante SPECT-TAC con 99mTc-(V) DMSA de metástasis óseas en paciente con cáncer medular de tiroides / Detection by SPECT-CT scan with 99mTc-(V) DMSA of bone metastases in patient with medullary thyroid cancer

El síndrome de neoplasia endocrina múltiple 2B (MEN 2B) es una entidad poco frecuente, que se caracteriza por la presencia de carcinoma medular de tiroides (CMT) en un 100% de los casos. El fenotipo de este síndrome incluye rasgos marfanoides y neuromas mucocutáneos. Describimos el caso de un paciente con un síndrome MEN 2B, al que se le diagnostica un cáncer medular de tiroides a partir del hallazgo de metástasis pulmonares y analizamos el papel del DMSA-V y de los nuevos sistemas híbridos SPECT-TAC en el estudio de extensión y seguimiento del CMT(AU)

Multiple endocrine neoplasia syndrome, type 2B (MEN 2B), is a rare entity characterized by the presence of medullary thyroid cancer in 100% of the cases. The phenotype of this syndrome consists in the presence of marfanoid features and mucocutaneous neuromas. We describe the case of a male patient with MEN 2B syndrome who was diagnosed with medullary thyroid cancer after lung metastases was found. We analyze the role of DMSA-V and the new hybrid SPECT-CT scan systems in the extension study and monitoring of medullary thyroid cancer(AU)

The Bnai Zion Planar Method: a simplified technique for the quantitation of the absolute renal uptake of (99m)Tc-DMSA in children.

AIM AND PURPOSE: Radionuclide imaging of the kidneys using dimercaptosuccinic acid chelate labeled with technetium-99m (Tc-DMSA) is a well-established method for evaluating the extent of kidney parenchymal involvement in the scenario of urinary tract infection and for the estimation of the functional renal mass. We have developed a simplified technique, Bnai Zion Planar Method (BZPM), to estimate absolute DMSA uptake by the kidneys, which uses a shorter time of acquisition and does not require cumbersome calculations of attenuation correction. The aim of this study was to validate this technique by comparing it with the Quantitative DMSA single-photon emission computed tomography (SPECT) (QDMSA) measurements as the reference method. METHODS: Sixty-one consecutive children (mean age 5.4+/-4.8 years) were included in the study. Absolute uptake of the radiopharmaceutical by the kidneys was measured using the QDMSA SPECT methods described earlier with data acquisition of 20 min. Kidney volumes and radioactivity concentration measurements were calculated on the reconstruction data using the threshold method. For the simplified technique (BZPM), a planar posterior view of the kidneys was acquired for 1 min at the end of the QDMSA SPECT study. RESULTS: In both kidneys we observed a significant strong correlation between the two methods. BZPM measurements were very similar to those obtained using the validated QDMSA method, as determined by linear regression analysis (Pearson's r=0.924, P<0.001), r(2)=0.854. The uptake according to QDMSA can be predicted by the uptake measured by the BZPM method using the following regression equation: QDMSA=0.445+1.061 BZPM. CONCLUSION: BZPM estimation in children using the newly proposed planar method was found to be nearly identical to the validated QDMSA SPECT method.

Evaluation of Tc-99m (V) DMSA binding to human plasma proteins.

As a critical step toward elucidating the mechanism of localization of Tc-99m (V) dimercaptosuccinic acid (DMSA), we investigated its binding and transport in blood in comparison with Ga-67 citrate. The studies were performed in vitro by incubating Tc-99m (V) DMSA with blood (one sample at 4 degrees Celcius and another at 37 degrees Celcius) to assess its binding to plasma proteins using ultrafiltration, dialysis, electrophoresis, gel filtration chromatography and affinity chromatography. A parallel experiment for determining the blood binding of Ga-67 citrate was performed using the same procedures. Using ultrafiltration, dialysis, electrophoresis and gel filtration chromatography, labeled plasma samples showed that protein binding for Tc-99m (V) DMSA was 45-54% at 37 degrees Celcius and 73-80% at 4 degrees Celcius. The figures for Ga-67 citrate were 43-53% at 37 degrees Celcius and 75-81% at 4 degrees Celcius. Electrophoresis showed that Tc-99m (V) DMSA was mostly bound to plasma albumin (36.05 +/- 2.48% at 37 degrees Celcius and 60.04 +/- 1.87% at 4 degrees Celcius), and that the proportion of Ga-67 radioactivity associated with beta-globulin was 34.23 +/- 1.37% at 37 degrees Celcius and 55.71 +/- 3.69% at 4 degrees Celcius. In affinity chromatography experiments, Tc-99m (V) DMSA did not bind to transferrin, unlike Ga-67 citrate. This study demonstrates that, at the radiopharmaceutical tracer level, most Tc-99m (V) DMSA in blood is protein-bound, primarily to albumin, but not to transferrin. In contrast, Ga-67 citrate was bound primarily to transferrin. The knowledge that albumin is the main transport protein of Tc-99m (V) DMSA may contribute to a better understanding of its biodistribution and pharmacokinetics.

Clinical differentiation of acute pyelonephritis from lower urinary tract infection in children.

BACKGROUND AND PURPOSE: To evaluate clinical variables for diagnosing childhood acute pyelonephritis (APN) when technetium-99m dimercaptosuccinic acid (DMSA) scintigraphy is not available. METHODS: We retrospectively reviewed the records of 590 children with febrile UTI seen from January 1999 to February 2004. On the basis of DMSA scintigraphy performed within 7 days after admission, they were divided into APN (n = 237) or non-APN (n = 353) groups. Gender, age, clinical presentation, absolute neutrophil count, C-reactive protein (CRP), urinalysis, culture, and sonographic findings were recorded from charts. RESULTS: A CRP level of > or =66.4 mg/L, in patients with >2 days prior to admission had a sensitivity of 71.6% and a specificity of 72.5% for APN. Similarly, a CRP of >27.3 mg/L in patients with < or =2 days prior to admission and a white cell count of >14,990/mm3 had sensitivities of 68.6% and 62.0% and specificities of 66.1% and 63.0%, respectively. Combining two or more variables did not result in better discrimination. CONCLUSIONS: If a DMSA scan is not available, it is reasonable to treat a febrile UTI as APN if the CRP is >66.4 mg/L in a patient with >2 days of fever or if the CRP is >27.3 mg/L in a patient febrile for < or =2 days.

Effect of a commercial extract of Paullinia cupana (guarana) on the binding of 99mTc-DMSA on blood constituents: An in vivo study.

We studied the influence of a commercial extract of Paullinia cupana (guarana) on the binding of technetium-99m-dimercaptosuccinic acid ((99m)Tc-DMSA) on blood constituents. Plasma (P) and blood cells (BC) from Wistar rats (control and treated) were separated. P and BC were precipitated with trichloroacetic acid (TCA) or ammonium sulphate (AS) and soluble (SF) and insoluble fractions (IF) isolated. The percentage of incorporated radioactivity (%ATI) in each fraction was determined. The treatment influenced the %ATI in IF-P and in IF-BC isolated by TCA precipitation.

Radiolabeled L-lysine for tumor imaging.

RATIONALE AND OBJECTIVES: The aims of this study were to label the versatile amino acid l-lysine with (99m)Tc using 2,3-dimercapto-succinic acid (DMSA) as a chelator, and to assess its tumor imaging feasibility under in vivo and in vitro conditions, and finally to determine the subcellular biodistribution of this radiopharmaceutical. MATERIALS AND METHODS: DMSA-l-lysine was chemically synthesized and labeled with sodium pertechnetate. Nuclear magnetic resonance (NMR) and mass spectral analysis of DMSA-l-lysine were conducted. Radiochemical purity was determined by thin-layer chromatography (TLC) and paper chromatography. Cellular uptake, competition and subcellular localization studies were performed in rat breast cancer cells (13762). In vivo studies of planar imaging and biodistribution studies were performed on female Fischer 344 rats. Medical Internal Radiation Dose (MIRD) dosimetry estimates were calculated. RESULTS: Radiochemical purity (determined by radio-TLC and high-performance liquid chromatography) of these compounds was >95%. (99m)Tc-DMSA-l-lysine showed good uptake in in vitro cell culture assays and uptake was reduced in competition studies. (99m)Tc-DMSA-l-lysine accumulates in the nucleus as much as in the cytoplasm and it was also shown that accumulation of the (99m)Tc-DMSA-l-lysine in the nucleus increases as a function of a time. There was an increase in tumor-to-blood and tumor-to-muscle count density ratios. Tumor/background ratios were 5.75 at 1 hour and 6.87 at 2 hours. In vivo tissue distribution studies revealed that radiation dosimetry of blood-forming organs were within radiation dose limits. CONCLUSION: DMSA-l-lysine kits can be labeled with (99m)Tc easily and efficiently, with high radiochemical purity and cost-effectiveness. In vitro cellular uptake and scintigraphic imaging studies demonstrated the pharmacokinetic distribution and feasibility of using (99m)Tc-DMSA-l-lysine for tumor imaging.

Relationship of cell proliferation (Ki-67) to 99mTc-(V)DMSA uptake in breast cancer.

INTRODUCTION: The aim of the present study was to identify the relationships between the uptake of radiotracers - namely pentavalent dimercaptosuccinic acid [(V)DMSA] and sestamibi (MIBI) - and the following parameters in primary breast cancer: steroid receptor concentrations (i.e. estrogen receptor [ER] and progesterone receptor [PR]), Ki-67 expression, tumor size, tumor grade, age, and levels of expression of p53 and c-erbB-2. In addition, by multivariate regression analysis, we further isolated those factors with independent associations with (V)DMSA and/or MIBI uptake in primary breast cancer. METHODS: Thirty-four patients with histologically confirmed breast carcinoma underwent preoperative scintimammography with technetium-99m (99mTc)-(V)DMSA and/or 99mTc-MIBI in consecutive sessions 10 and 60 min after administration of 925-1110 MBq of each radiotracer. The tumor-to-background ratio was calculated and correlated with the presence of ER, PR, Ki-67, tumor size, tumor grade, p53, and c-erbB-2. ER, PR, p53, and c-erbB-2 were determined immunohistochemically. The analysis included tumor-to-background ratio of (V)DMSA and MIBI uptake as dependent and all of the other parameters as independent variables. RESULTS: Correlation was positive between Ki-67 and (V)DMSA (r = 0.37 at 10 min, P = 0.038; r = 0.42 at 60 min, P = 0.018) and inverse between PR and (V)DMSA uptake (r = -0.46 at 10 min, P = 0.010; r = -0.51 at 60 min, P = 0.003). Multivariate regression analysis demonstrated a positive correlation between Ki-67 and (V)DMSA at 60 min (P = 0.045). Ki-67 was not significantly correlated with MIBI uptake, whereas tumor size was positively correlated with MIBI uptake at 60 min both in univariate (r = 0.45, P = 0.027) and multivariate analysis (P = 0.024). Negative correlations were observed between (V)DMSA uptake and ER, as well as between ER/PR and MIBI uptake, but these were not significant. CONCLUSION: Ki-67 appears to represent the major independent factor affecting (V)DMSA uptake in breast cancer. Tumor size was the only independent parameter influencing MIBI uptake in breast cancer. (V)DMSA appears to have an advantage over MIBI in that it can be used to visualize tumors with intense proliferative activity, and thus it can identify those tumors that are more aggressive.

The multidrug resistance of in vitro tumor cell lines derived from human breast carcinoma MCF-7 does not influence pentavalent technetium-99m-dimercaptosuccinic Acid uptake.

The main causes of multidrug resistance (MDR) are overexpression of P-glycoprotein (P-gp) and multidrug resistance-associated protein isoform 1 (MRP1) often associated with high levels of glutathione (GSH). We investigated whether MDR phenotype can influence Tc-99m-(V)-DMSA [pentavalent technetium-99m-dimercaptosuccinic acid] entry by comparing its uptake with that of Tc-99m-sestamibi (MIBI) on an in vitro model of sensitive (MCF-7) and variant resistant cell lines. Drug resistance was assessed by immunoblotting, GSH measurement, and 3-[4,5-dimethylthiazol-2-yl]-2,5,diphenyl tetrazolium bromide (MTT) assay. To correlate MDR phenotype with tracer accumulation, uptakes were performed with and without P-gp and MRP1 inhibitors and after GSH modulation. Similar accumulation of Tc-99m-(V)-DMSA was observed in all cell lines and the use of MDR reversals did not enhance its uptake. Our results demonstrate clearly that Tc-99m-(V)-DMSA uptake is not related to either P-gp and MRP1 expression, or GSH levels. In contrast, Tc-99m-MIBI accumulation is inversely proportional to the cell MDR phenotype. The combination of Tc-99m-(V)-DMSA and Tc-99m-MIBI may be a useful tool for noninvasive detection of malignant sites and their chemoresistance status.

Unilateral autosomal dominant polycystic kidney disease with contralateral renal agenesis: a case report.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease. There are some reports in the literature concerning unilateral ADPKD. However, in adults, only a few cases of unilateral ADPKD with agenesis of contralateral kidney have been reported. We present a case of unilateral ADPKD with agenesis of contralateral kidney in a 66-yr-old man. Radiographic images showed the enlarged right kidney with multiple variable-sized cysts and the absence of the left kidney. The diagnosis of ADPKD was confirmed by the family screening. The patient received maintenance hemodialysis for endstage renal disease. We report a case of unilateral ADPKD associated with contralateral renal agenesis in a 66-yr-old male patient with a literature review.

Unilateral Autosomal Dominant Polycystic Kidney Disease with Contralateral Renal Agenesis: A Case Report

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease. There are some reports in the literature concerning unilateral ADPKD. However, in adults, only a few cases of unilateral ADPKD with agenesis of contralateral kidney have been reported. We present a case of unilateral ADPKD with agenesis of contralateral kidney in a 66-yr-old man. Radiographic images showed the enlarged right kidney with multiple variable-sized cysts and the absence of the left kidney. The diagnosis of ADPKD was confirmed by the family screening. The patient received maintenance hemodialysis for endstage renal disease. We report a case of unilateral ADPKD associated with contralateral renal agenesis in a 66-yr-old male patient with a literature review.