DMSA Uptake Research Articles

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

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. 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. 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 ± 3.4, with spilt renal function 79.2 ± 14.7 and ARU (%) in right kidneys 16.2 ± 3.4 with spilt renal function 77.5 ± 19. Absolute renal uptake of Tc-99m DMSA in left kidneys was 17.5 ± 3.2 and in right kidneys 17.9 ± 4.5 with spilt renal function 81.8 ± 10.7 and 79.3 ± 13.8 for left and right kidney, respectively. Statistical analysis showed strong Pearson correlation. 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

IntroductionWe 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.

Using 99mTc-(V)-DMSA to follow the vascular calcification process in vascular smooth muscle cells based on pit-1 expression.

Vascular calcification is an established feature of atherosclerosis process. The sodium/phosphate transporter PiT-1 acts as a biosensor in vascular calcification of VSMCs. [99mTc]-Pentavalent dimercaptosuccinic acid (99mTc-(V)-DMSA) was mediated by PiT-1 transporter in tumoral cells and we propose its evaluation in a vascular calcification in vitro model. The aim of this study was to determine if 99mTc-(V)-DMSA can follow the vascular calcification process in vascular smooth muscle cells (VSMCs) based on PiT-1 expression. From a rat aortic VSMC cell line (A7r5), we set up a model of calcification within 7 days using a calcifying medium containing a high inorganic phosphate concentration. Phosphocalcic deposits were monitored with Alizarin red and Von Kossa staining and with phase contrast microscopy. PiT-1 expression was evaluated with an immunofluorescence assay and osteopontin expression, with whole cell ELISA assay. 99mTc-(V)-DMSA uptake was measured in control and calcifying conditions and compared with optical microscopy evaluation. Under hyperphosphatemia conditions, the VSMC cells progressively overexpressed osteopontin protein, PiT-1 transporter, and synthetized mineralized matrix with phosphocalcic deposition. 99mTc-(V)-DMSA uptake was to 2.8±2.08%DA/mg-protein in control cells and 42±24%DA/mg-protein in calcified cells (P<0.001). PiT-1 inhibition with phosphonoformic acid completely reverse the calcium deposition as well as the 99mTc-(V)-DMSA uptake. These results demonstrated that 99mTc-(V)-DMSA in-vitro uptake is mediated by PiT-1 transporter and follow the VSMC calcification process. These preliminary in-vitro results showed 99mTc-(V)-DMSA uptake follow the phospho-calcic deposition mediated by PiT-1 transporter. This radiotracer may have some potential to detect changes of VSMC metabolism occurring in the atherosclerosis process.

The value of quantitative pentavalent 99mTc-dimercaptosuccinic acid scan in predicting progression-free survival and overall survival in patients with glioblastoma multiforme

AbstractAim:Glioblastoma multiforme (GBM) is the commonest and the most aggressive primary brain tumour. Pentavalent 99mTc-dimercaptosuccinic acid (99mTc (V)-DMSA) has been found to be a tumour-seeking agent. Pre-radiotherapy 99mTc (V)-DMSA positive scan was found to be significantly correlated with poor progression-free survival (PFS) and overall survival (OS). This study aims at evaluating the impact of quantitative 99mTc (V)-DMSA tumour uptake before and after radiotherapy on PFS and OS in patients with GBM.Methods:A prospective study included 40 patients with GBM. Single-photon emission computed tomography studies were done before and after adjuvant radiotherapy and were qualitatively and quantitatively evaluated. The retention index (RI) of the viable tumour was correlated with PFS and OS.Results:The qualitative enhancement of 99mTc (V)-DMSA uptake either positive or negative was significantly correlated with PFS at both early and late images (p-values 0·04 and 0·026, respectively) and OS only in the late image (p-value 0·036). The calculated ion/non-lesion ratios at late images were statistically correlated with PFS and OS (p-values 0·021 and 0·025, respectively). The baseline RI had significant correlation with PFS only (p-value 0·01).Conclusion:The degree of 99mTc (V)-DMSA scan positivity is a poor prognostic factor for PFS and OS in GBM patients.

Evaluation of the protective effect of edaravone on doxorubicin nephrotoxicity by [99mTc]DMSA renal scintigraphy and biochemical methods.

To evaluate the nephroprotective effect of edaravone on doxorubicin-induced nephrotoxicity. In this experimental study, twenty-eight Wistar male rats were used. The rats were separated into 4 groups (n = 7); group І (control), rats were treated with saline (4ml/kg) and group ІІ (doxorubicin), nephrotoxicity was induced by three doses of 18mg/kg/i.p. doxorubicin, at a 24-h interval on the 12th, 13th, and 14th days. Group ІІІ (edaravone), rats were treated with edaravone (30mg/kg/for 14days), and group ІV (edaravone + doxorubicin), rats were treated with edaravone (30mg/kg/for 14days) and doxorubicin were injected (18mg/kg/for 3days; at a 24-h interval on the 12th, 13th, and 14th days). On the 15th day of the experiment, technetium-99m-labeled dimercaptosuccinic acid ([99mTc]DMSA) uptake was obtained in both kidneys and biochemical parameters from serum and kidney tissue were measured. Doxorubicin led to nephrotoxicity through elevation of serum blood urea nitrogen (BUN), creatinine and tumor necrosis factor-α (TNF-α), nitric oxide (NO), and interleukin-6 (IL-6) in kidney tissue and decreased [99mTc]DMSA uptake level in the kidney when compared with control group (p < 0.01). Pretreatment edaravone significantly decreased BUN and creatinine, also kidney tissue TNF-α, IL-6, NO, and increased [99mTc]DMSA uptake level compared with the doxorubicin. Edaravone has a significant nephroprotective effect through the attenuation of oxidative stress and inflammatory markers during doxorubicin-induced nephrotoxicity in rats.

The role of Thallium-201 scintigraphy and Tc-99m pentavalent dimercaptosuccinic acid in diagnosis and grading of chondrosarcoma

PurposeDistinguishing between enchondromas and low-grade (grade 1) chondrosarcomas can be challenging. The aim of this study was to investigate the role of Thallium-201 scintigraphy and Technetium-99 m pentavalent dimercaptosuccinic acid (Tc-99 m DMSA (V)) in the diagnosis and grading of chondrosarcomas. Methods232 consecutive patients with pathologically proven cartilaginous tumours between the years 2000 and 2018 were evaluated. We included 197 patients (101 males and 96 females; median age 50 years; range 15–86 years) who underwent Thallium-201(n = 193) and/or Tc-99 m DMSA (V) scanning (n = 67). Increased uptake was defined as uptake greater than background. The reference standard was the histopathological assessment based on a grading system (grade 1–3). Data was analysed using multivariate modelling. ResultsThere were 46 patients with enchondromas and 151 with chondrosarcomas. Of those, 64 (enchondroma n = 21, chondrosarcoma n = 43) underwent both Thallium-201 and Tc-99 m DMSA (V). Thallium-201 uptake had 7.92 times greater odds of grade 1 chondrosarcomas than enchondromas. Thallium-201 uptake was significantly associated with the odds of a higher grade chondrosarcoma (grade 2–3). DMSA (V) positivity was associated with 4.75 times the odds of a chondrosarcoma diagnosis over enchondroma (p = 0.024). DMSA (V) uptake revealed no association with chondrosarcoma grading. ConclusionLow-grade chondrosarcomas continue to pose a diagnostic dilemma. Thallium-201 scans may identify malignancy in benign appearing tumours as well as differentiate between low-grade and high-grade chondrosarcomas in said malignancies. DMSA (V) may be useful in distinguishing between benign and malignant entities as a whole.

Protective effect of melatonin and agomelatine on adriamycin-induced nephrotoxicity in rat model: a renal scintigraphy and biochemical study.

We aimed to determine the possible protective effects of melatonin and agomelatine on an animal model of adriamycin nephrotoxicity by 99mTc DMSA renal scintigraphy and biochemical methods. Ten weeks old 49 male Wistar rats were randomly separated into seven groups; namely control (CON), adriamycin (ADR), melatonin (MEL), agomelatine (AGO), melatonin + adriamycin (MEL+ADR), agomelatine + adriamycin (AGO+ADR) and melatonin + agomelatine + adriamycin (MEL+AGO+ADR) groups. Nephrotoxicity was induced by a three-dose of 18 mg/kg adriamycin, i.p. at a 24 h interval on the 5th, 6th and 7th days. A dose of melatonin and agomelatine (40 mg/kg/i.p, the same doses) were injected for 7 days before and after the injected of ADR (18 mg/kg, i.p.), respectively. On the 8th day of the experiment, all animals were evaluated and scintigraphic and biochemical parameters were assessed, respectively. ADR significantly increased blood urea nitrogen (1040 %) and plasma creatinine (1020 %), and decreased 99mTc DMSA uptake levels (59 %) compared to the control (p < 0.001). Pretreatment with MEL, AGO, MEL+AGO mitigated these abnormalities produced by ADR in the kidney (p < 0.001). 99mTc DMSA for the early determination of ADR-induced nephrotoxicity had an important role. Also, a significant correlation was found between biochemical and scintigraphy parameters. Adriamycin caused significant damages to kidneys that were reduced with MEL and AGO (Tab. 2, Fig. 3, Ref. 39).

Scintigraphic, histopathologic and biochemical evaluation of lycopene effects on renal ischemia reperfusion injury in rats

Introduction/Objective. Medical protection of kidneys against ischemia reperfusion injury is very important. Many agents have been used for the protection of ischemia reperfusion renal tissue injury. We aimed to evaluate the radioprotective effect of lycopene on kidneys in ischemia reperfusion injury with histopathological, biochemical, and scintigraphic parameters. Methods. Twenty-one Wistar male albino rats were divided into the following three groups: lycopene, control, and sham group. In the lycopene group, lycopene was started three days before right renal ischemia reperfusion injury and continued for 15 days. In the control group, right renal ischemia reperfusion injury was applied with no medication. In the sham group, neither right renal ischemia reperfusion injury nor medication were applied. On the 15th day, all rats were sacrificed after 99mTc-dimercaptosuccinic acid (DMSA) scintigraphies were taken. Histopathological, biochemical, and scintigraphic evaluations were made. Results. The histopathological score was lower in the lycopene group. In biochemical analysis, myeloperoxidase levels were lower in the lycopene group than in the control group, but not statistically significant. Malondialdehyde and nitrite levels were lower in the lycopene group than in the control group. The postoperative mean 99mTc-DMSA uptake values were 44.82 ? 1.84 in the lycopene group, 38.92 ? 1.17 in the control group, and 50.21 ? 1.35 in the sham group. DMSA uptake values were higher in the lycopene group than in the control group. Conclusion. Lycopene seems to be an effective agent for protection of kidneys in ischemia reperfusion injury as demonstrated by the histopathological, biochemical, and scintigraphic parameters.

Estimation of Absolute Renal Uptake of 99mTc DMSA in Potential Kidney Donors and its Accuracy in Determination of Split Function

Estimation of Absolute Renal Uptake of 99mTc DMSA in Potential Kidney Donors and its Accuracy in Determination of Split Function

Assessment of Tracer 99mTc(V)-DMSA Uptake as a Measure of Tumor Cell Proliferation In Vitro

PurposeTo examine whether 99mTc(V)-DMSA could be used as a non-invasive measure of cancer cell proliferation.MethodsHuman 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 99mTc(V)-DMSA in media for 60 min at 37°C. DNA synthesis was analysed by quantification of the S phase using flow cytometry, [methyl-3H]thymidine incorporation and expression of proliferation markers PCNA and Ki-67 using realtime PCR. One way ANOVA was used to compare groups.ResultsIn all cell lines rates of 99mTc(V)-DMSA uptake were inversely related to cell density. This was paralleled by similar trends in S phase proportions, [methyl-3H]thymidine incorporation and expression of PCNA and Ki-67.ConclusionRates of 99mTc(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.

Assessment of Warm and Cold Ischemia on Functions of the Operated Kidney with &amp;lt;sup&amp;gt;99m&amp;lt;/sup&amp;gt;Tc-DMSA in Renal Masses: A Prospective and Randomized Study

Objective: To examine the effect of warm and cold ischemia on functions of the operated kidney in cases with a normal contralateral kidney undergoing nephron sparing surgery. Methods: This study enrolled 40 patients with a normal contralateral kidney and without a renal function threatening risk factor, who were operated with NSS. The patients were randomized at admission. They were divided into 2 equal groups as warm and cold ischemia. An ice application for 10 minutes was done to cold ischemia group after clamping renal artery. Renal functions were evaluated with Technesium-99m-Dimercaptosuccinic Acid (DMSA) and serum creatinine at the preoperative and postoperative (day 1, day 15, month 6, and month 12) period. Statistical analysis was done with Mann Whitney U test, Wilcoxon Signed Rank test, and Fredman test. A p value below 0.05 was considered statistically significant. Results: There were no significant differences between the groups in terms of age, body mass index, ischemia time, tumor size, amount of hemorrhage, and procedure time. Both groups had a significantly higher DMSA uptake at the preoperative period compared with the postoperative period (postoperative day 1, day 15, month 6, and month 12) (p 0.001). However, both groups had similar DMSA uptake results at the postoperative period. Preoperative and postoperative creatinine levels were not significantly different from each other in both groups. Conclusion: Based on tumor localization, nephron sparing surgery without use of superficial cooling appears as a viable option for small renal masses.

99mTc-DMSA (V) in Evaluation of Osteosarcoma: Comparative Studies with 18F-FDG PET/CT in Detection of Primary and Malignant Lesions

To evaluate the role of 99mTc-DMSA (V) and [18F]FDG PET-CT in management of patients with osteosarcoma, 22 patients were included in our study. All patients underwent both 99mTc-DMSA (V) and whole-body [18F]FDG PET-CT scans within an interval of 1 week. 555–740 MBq of 99mTc-DMSA (V) was injected i.v. the whole-body planar, SPECT images of primary site and chest were performed after 3-4 hours. [18F]FDG PET-CT images were obtained 60 minutes after i.v. injection of 370 MBq of F-18 FDG. Both FDG PET-CT (mean SUVmax = 7.1) and DMSA (V) scans showed abnormal uptake at primary site in all the 22 patients (100% sensitivity for both). Whole-body PET-CT detected metastasis in 11 pts (lung mets in 10 and lung + bone mets in 1 patient). Whole-body planar DMSA (V) and SPECT detected bone metastasis in one patient, lung mets in 7 patients and LN in 1 patient. HRCT of chest confirmed lung mets in 10 patients and inflammatory lesion in one patient. 7 patients positive for mets on DMSA (V) scan had higher uptake in lung lesions as compared to FDG uptake on PET-CT. Three patients who did not show any DMSA uptake had subcentimeter lung nodule. Resuts of both 99mTc-DMSA (V) (whole-body planar and SPECT imaging) and [18F]FDG PET-CT were comparable in evaluation of primary site lesions and metastatic lesions greater than 1 cm. Though 99mTc-DMSA (V) had higher uptake in the lesions as compared to [18F]FDG PET-CT, the only advantage [18F]FDG PET-CT had was that it could also detect subcentimeter lesions.

Patients with a history of infection and voiding dysfunction are at risk for recurrence after successful endoscopic treatment of vesico ureteral reflux and deserve long-term follow up

Aim of the Study:Subureteral endoscopic injection of a bulking agent is an attractive alternative to open surgery or antibiotic prophylaxis for vesico ureteral reflux (VUR). Little information is available about long-term risk of recurrence after an initially successful treatment. Aim of this paper was to review short- and long-term success rate of endoscopic treatment in a single Center series after risk stratification of individual patients.Materials and Methods:The records of 126 patients who underwent Deflux injection for primary VUR were examined. Indications to treatment were an unvaried high grade VUR (IV-V) at 1 year from diagnosis and/or and recurrent urinary tract infection (UTI) on antibiotic prophylaxis even in the presence of mild grade VUR (III grade). Gender, age and mode of diagnosis, infections (UTI), voiding dysfunctions, VUR grade and side, renal function, number of treatments were correlated to outcome. Long-term evaluation was planned at a minimum of 1 year from the last negative post-injection cystogram (MCUG). A new MCUG and DMSA scan were also offered to those complaining new UTI episodes. Late recurrences were correlated to history and grade of reflux. Data were analyzed with Graph Pad Instat software; the Chi-square test was used for univariate comparisons, the Fisher's exact test for categorical variables.and multiple regression tests for factors influencing outcome.Results:M/F ratio was 62 to 64; median age at diagnosis was 28 months. VUR affected 198 renal units. Preinjection VUR grade was I in 1, II in 27, III in 107, IV in 59, and V in 4 units. Reduced DMSA uptake was evidenced in 51 units and scarring in 24. Median age at treatment was 34.5 months, for persistent high grade VUR (IV–V) in 55 patients and recurrent IVU in 92. Two hundred sixty seven injections were performed on 198 ureters. Complete resolution was documented by MCUG at 3-5 months in 68%, low grading < II in 20%, persistence or unsignificant reduction in 11%. Preoperative recurrent UTI, higher grade VUR, and bilaterality were correlated to a poorer surgical outcome. Among 80 successfully treated cases, 12 complained of persistent UTI. Recurrence of VUR was demonstrated in 31% of them. Deteriorated uptake or additional scarring in 25% was independent from VUR recurrence. Preoperative recurrent UTI and voiding dysfunction correlated significantly to late outcome.Conclusions:Preoperative recurrent IVU, together with high-grade reflux, seem to correlate to lower success rate of Deflux injection for primary VUR. Even after successful endoscopic treatment, long-term surveillance may be needed among these cases, mainly if voiding dysfunction is also recorded. Late recurring VUR must be actively excluded in case of new IVU episodes.

Increased Breast Density Correlates with the Proliferation-Seeking Radiotracer99mTc(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.

Renal Parenchymal Damage After Percutaneous Nephrolithotomy with One-Stage Tract Dilation Technique: A Randomized Clinical Trial

To compare the effects of one-stage vs gradual dilation techniques during percutaneous nephrolithotomy (PCNL) on postoperative renal scar formation and overall renal function. Of 152 adult patients who underwent surgery during the study period, 48 were randomized into two groups. In group 1 (n=19), gradual tract dilation with Alken metallic dilators was used, and in group 2 (n=29), one-stage tract dilation was used. We compared patient demographics, intraoperative and preoperative parameters, postoperative overall renal function, and renal scar formation on the target renal pole. Access time (P=0.001; 95% confidence interval [CI]: 3.19-6.30) and radiation exposure during access (P=0.03; 95% CI: 0.03-0.66) were significantly shorter in group 2. In group 1, the decrease in mean technetium-99m dimercaptosuccinic acid (99m-Tc DMSA) uptake from 44.1±20.1% to 43.4±19.6% 4 weeks postoperatively (-0.7%±0.5%; P=0.27; 95% CI: -0.56-1.93) was not significant. In group 2, however, there was a significant decrease in post-PCNL 99m-Tc DMSA uptake 2 (-2.4±0.3%, from 50.1±13.5% to 47.7±13.8%; P=0.001; 95% CI: 1.13-3.66). Four weeks after surgery, new scar formation or progression of the preoperative scar at the site of access were seen in 14 of 29 (48.3%) patients who were treated with one-stage dilation whereas only 2 of 19 (11.0%) patients who were treated with gradual dilation developed new scarring at the access site (P=0.007). Although the one-stage tract dilation technique reduced radiation exposure and access time, in the short term, it may cause more parenchymal damage than the gradual dilation technique.

L-Carnitine Protection Against Cisplatin Nephrotoxicity In Rats: Comparison with Amifostin Using Quantitative Renal Tc 99m DMSA Uptake

Objective: In this study, we aimed to investigate the cytoprotective effect of L-carnitine against cisplatin-induced nephrotoxicity and to compare its efficacy with that of amifostin by quantitative renal Tc 99m DMSA uptake. Material and Methods: Male Wistar rats were randomly divided into six groups of six animals each. 1) Control (saline; 5 ml/kg intraperitoneally); 2) L-carnitine (CAR; 300 mg/kg intraperitoneally); 3) Amifostine (AMI; 200 mg /kg intraperitoneally); 4) Cisplatin (CIS;7 mg/kg intraperitoneally); 5) Cisplatin plus L-carnitine (CIS + CAR); 6) Cisplatin plus amifostine (CIS + AMI). L-carnitine and amifostine were injected 30 minutes before cisplatin in Group 5 and 6. Tc 99m DMSA, 7.4 MBq/0.2 ml, was injected through the tail vein 72 hours after the drug administration. Rats were killed and kidneys removed by dissection 2 hours after the injection of the radiopharmaceutical. The percentage of the injected dose per gram of kidney tissue (%ID/g) was calculated. Renal function was monitored by measuring BUN and plasma levels of creatinine. Lipid peroxidation and glutathione content were determined by measuring malondialdehyde (MDA) and reduced glutathione (GSH) in kidney tissue homogenates. Results: Tc 99m DMSA uptake per gram tissue of the kidney as %ID/g was 29.54±4.72, 29.86 ± 7.47 and 26.37 ± 4.54 in the control, CAR and AMI groups respectively. %ID/g was the lowest of all the groups, 11.60±3.59 (p<0.01), in the cisplatin group. Carnitine or amifostine administration 30 minutes before cisplatin injection resulted a significant increase in %ID/g, 21.28±7.73 and 18.97±3.24 respectively, compared to those of cisplatin-treated rats (p<0.002). A marked increase in plasma BUN and creatinine indicating nephrotoxicity and acute renal failure was observed in the cisplatin-treated group. MDA and GSH levels were concordant with cisplatin-induced oxidative stress in the kidney tissue.Conclusion: The results showed that L-carnitine significantly attenuates the cisplatin-induced nephrotoxicity as amifostin.Conflict of interest:None declared.

Urinary levels of TGF β-1 and of cytokines in patients with prenatally detected nephrouropathies

This study aimed to identify noninvasive biomarkers of clinically significant nephrouropathies in patients with antenatal renal and/or urinary tract alterations. Spot-urine levels of interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) were measured in 100 patients with antenatal detected nephrouropathies. Patients were divided in idiopathic hydronephrosis (n = 47), urinary tract malformations (n = 35), and dysplastic kidneys (n = 18). Urinary concentrations of TGF-β1, IL-6, and TNF-α were compared between groups according to clinical and image findings. Receiver-operating characteristic (ROC) curves were analyzed for the overall diagnostic accuracy of TGF-β1, IL-6, and TNF-α levels in discriminating infants with nephrouropathies. No significant differences in urinary TGF- β1, IL-6, and TNF-α levels were found in the comparison between the groups. TGF-β1 levels tended to be higher in patients with renal hypodysplasia compared to idiopathic hydronephrosis (p = 0.07). Twenty-nine patients had reduced DMSA uptake. In these cases, absolute urinary concentration of TGF-β1 and levels standardized for creatinine were significantly higher than in patients with normal DMSA uptake, while IL6 and TNF-α did not differ between groups. Urinary cytokine measurements were not useful as a screening test for clinically significant nephrouropathies. Conversely, increased concentrations of TGF-β1 pointed out to renal damage as indicated by reduced DMSA uptake.

Ibuprofen Induces Reduction of the Proliferation-Seeking Radiotracer 99m Tc-(V)DMSA Uptake in Severe Epithelial Breast Hyperplasia without Atypia

The purpose of this study was to investigate if ibuprofen intake can influence mammary uptake of the proliferation-seeking radiotracer technetium 99m-pentavalent dimercaptosuccinic acid (99mTc-(V)DMSA) in women with severe epithelial and atypical epithelial breast hyperplasia. Eight patients with histologically confirmed severe epithelial breast hyperplasia with (n = 4) and without atypia (n = 4) were submitted prospectively to 99mTc-(V)DMSA scintimammography before and after a 4-week course of 400 mg ibuprofen daily oral intake. Lesion to background ratios 60 minutes postinjection were calculated and compared (t-test) before and after ibuprofen administration. Prior to ibuprofen, the patients with severe epithelial hyperplasia displayed a significantly higher 99mTc-(V)DMSA uptake ratio compared to those with atypical epithelial hyperplasia (2.40 ± 0.32 vs 1.67 ± 0.09, respectively; p = .003). They also exhibited a more substantial percent decline in tracer uptake postibuprofen compared to women with atypical epithelial hyperplasia (62.0 ± 7.1 vs 15.0 ± 0.2, respectively; p = .001). Ibuprofen induces significant uptake reduction of the proliferation-seeking radiotracer 99mTc-(V)DMSA in severe epithelial breast hyperplasia without atypia. This agent could therefore constitute a potential imaging tool for monitoring chemoprophylaxis effectiveness in women at the early stages of malignant transformation.

The Bnai Zion Planar Method: a simplified technique for the quantitation of the absolute renal uptake of 99mTc-DMSA in children

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. 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. 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. BZPM estimation in children using the newly proposed planar method was found to be nearly identical to the validated QDMSA SPECT method.

Abstract 2381: Neoangiogenesis correlates with increased breast density, calcitonin gene related peptide positivity and cell proliferation seeking radiotracer uptake in mixed invasive ductal associated with in situ, but not in pure invasive breast carcinoma

Abstract Aim: To assess neoangiogenesis in relation to breast density (BD), calcitonin gene related peptide (CGRP), cell proliferation seeking radiotracer 99mTc-(V)DMSA uptake (SMM) in invasive ductal associated with extensive in situ carcinoma (DCIS + IDC) and in pure invasive breast carcinoma (IDC). Methods: 20 patients with histologically confirmed mixed DCIS + IDC (n=10) and pure IDC (n=10) were submitted preoperatively to mammography and scintimammography. The percentage of breast density (BD) and the percentage of tracer uptake (SMM) were calculated with computer assisted methods. CGRP and the number of newly formed blood vessels (NBV) were immunohistochemicaly assessed. NBV, BD, CGRP, and SMM were compared (t-test) between the two groups. Linear regression analysis was performed between NBV, BD, CGRP and SMM in both groups. Results: NBV, BD, CGRP and SMM were significantly higher in mixed DCIS + IDC as compared to pure IDC (32.1±10.4 vs 24.3±5 p=0.048, 35.2 ± 6.9 vs 25.6±10.7 p=0.028, 25.5±7.6 vs 17±7.8 p=0.024, 26.75±4.09 vs 11.34±8.5 p=0.0009). NBV was strongly correlated with BD and CGRP in the DCIS component of the mixed group (r=0.933 p&amp;lt;0.001, r=0.793 p&amp;lt;0.01 respectively). BD was also significantly correlated with CGRP and SMM in the DCIS component of the same group (r=0.974 p&amp;lt;0.001, r=0.728 p&amp;lt;0.05 respectively). In contrast, no significant correlation(NS) was found between NBV and BD, CGRP or between BD and CGRP, SMM in both the IDC component of mixed group and pure IDC group (r=0.388 NS, r=0.391 NS, r= − 0.597 NS, r= − 0.352 NS in the IDC component of mixed group; r=0.584 NS, r= 0.297 NS, r= − 0.574 NS, r= −0.294 NS in pure IDC respectively). Conclusion: Mixed DCIS + IDC lesions exhibit significantly increased NBV, BD, CGRP and SMM values as compared to those of IDC lesions. The strong correlation between neoangiogenesis and the other parameters in the mixed group indicates that the mixed DCIS + IDC constitutes a strictly different entity from pure IDC, more aggressive and probably originates from the stroma through the CGRP pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2381.