Low-dose angiotensin AT1 receptor ß-arrestin-biased ligand, TRV027, protects against cisplatin-induced nephrotoxicity.

BACKGROUND: Recruitment of ß-arrestin to G protein-coupled receptors (GPCRs), initially described to cause receptor desensitization, has recently been shown to take active roles in cell signaling. We investigated the effects of TRV027, an angiotensin AT1 receptor ß-arrestin-biased ligand, as well as losartan and valsartan on cisplatin-induced kidney injury. METHOD: Male Sprague-Dawley rats were treated with angiotensin receptor ligands (1 or 10 mg/kg/day) with or without cisplatin, and kidney variables were monitored using animal SPECT, histopathology, and serum parameters. RESULTS: TRV027, losartan, and valsartan did not alter renal dimercaptosuccinic acid (DMSA) uptake, histopathological manifestations of kidney injury, blood urea nitrogen (BUN), and creatinine or Na+ and K+ levels, per se. However, when rats co-treated with cisplatin and either of the AT1 receptor blockers at higher doses, we observed aggravation of cisplatin-induced reduction of radiotracer uptake but improvement of cisplatin-induced hypokalemia, and insignificant effect on histological findings. Furthermore, we noted an additional increase in cisplatin-induced augmentation of BUN and creatinine levels in cisplatin plus valsartan group. TRV027 (1 mg/kg/day) inhibited cisplatin adverse effects on radiotracer uptake, kidney histology, BUN, and creatinine as well as electrolyte levels, but it failed to produce protective effects at higher dose (10 mg/kg/day). CONCLUSION: Low-dose TRV027 may offer potential benefits in kidney injury due to cisplatin.

Correction to: Scintigraphic evaluation of remote perconditioning protection against unilateral renal ischemia/reperfusion injury in rats: a longitudinal study.

The original article was published with incorrect article title.

Scintigraphic evaluation of remote pre-conditioning protection against unilateral renal ischemia/reperfusion injury in rats: a longitudinal study.

PURPOSE: To determine the role of remote perconditioning (RPeC) on renal function and histology in an animal model of unilateral renal ischemia and reperfusion (IR) injury. METHODS: Rats were subjected to 60 min unilateral renal ischemia. RPeC protocol was the application of four cycles of 5 min IR of left femoral artery during renal ischemia. Assessments of histological changes and renal function were made 24 h, 1 week, or 3 weeks later. 99mTc-DMSA scan was performed using a small-animals SPECT system. RESULTS: 24-h reperfusion decreased the 99mTc-DMSA uptake in the left kidney compared to the intact kidney of control animals. RPeC group has higher uptake compared to the IR group. After 1 week and 3 weeks, uptakes were gradually increased in both groups and no differences were observed. Severe morphological changes in the ischemic kidneys of both groups were observed after 24 h which attenuated after 1 week and 3 weeks. Moreover, no differences in creatinine and BUN levels between IR-treated and intact animals were observed. CONCLUSION: These data suggest that RPeC exerts a partially transient improvement in the renal function in the first day after reperfusion. However, long-term follow-up study showed no beneficial effects of RPeC. Moreover, noninvasive 99mTc-DMSA scan revealed a suitable tool in the follow-up evaluation of recovery process in the unilateral renal IR injury models.

A Monte Carlo study on the performance evaluation of a parallel hole collimator for a HiReSPECT: A dedicated small-animal SPECT.

Collimator geometry has an important contribution on the image quality in SPECT imaging. The purpose of this study was to investigate the effect of parallel hole collimator hole-size on the functional parameters (including the spatial resolution and sensitivity) and the image quality of a HiReSPECT imaging system using SIMIND Monte Carlo program. To find a proper trade-off between the sensitivity and spatial resolution, the collimator with hole diameter ranges of 0.3-1.5 mm (in steps of 0.3 mm) were used with a fixed septal and hole thickness values (0.2 mm and 34 mm, respectively). Lead, Gold, and Tungsten as the LEHR collimator material were also investigated. The results on a 99mTc point source scanning with the experimental and also simulated systems were matched to validate the simulated imaging system. The results on the simulation showed that decreasing the collimator hole size, especially in the Gold collimator, improved the spatial resolution to 18% and 3.2% compared to the Lead and the Tungsten, respectively. Meanwhile, the Lead collimator provided a good sensitivity in about of 7% and 8% better than that of Tungsten and Gold, respectively. Overall, the spatial resolution and sensitivity showed small differences among the three types of collimator materials assayed within the defined energy. By increasing the hole size, the Gold collimator produced lower scatter and penetration fractions than Tungsten and Lead collimator. The minimum detectable size of hot rods in micro-Jaszczak phantom on the iterative maximum-likelihood expectation maximization (MLEM) reconstructed images, were determined in the sectors of 1.6, 1.8, 2.0, 2.4 and 2.6 mm for scanning with the collimators in hole sizes of 0.3, 0.6, 0.9, 1.2 and 1.5 mm at a 5 cm distance from the phantom. The Gold collimator with hole size of 0.3 mm provided a better image quality with the HiReSPECT imaging.

Serological, pathological, and scintigraphic assessment of Hemiscorpius lepturus effects on renal dysfunction in rats.

OBJECTIVES: Hemiscorpius lepturus is one of the dangerous scorpions of Iran leading to acute kidney injury (AKI) especially in infants. The purpose of this animal study was to compare the serological, pathological and scintigraphic data to quickly predict the occurrence of this disorder. MATERIALS AND METHODS: In two groups of animals, each contained five rats, H. lepturus venom (1200 µg/Kg) were injected intravenously via the tail vein. At three hours and one week later, 99m Tc-DMSA (3 mCi) was intravenously injected and renal scintigraphy was performed after an hour. Moreover, plasma levels of creatinine, sodium, potassium, and blood urea nitrogen (BUN) were measured. At the end of the study, renal tissues were excised and prepared to perform pathological evaluation after Hematoxylin and Eosin staining. RESULTS: All serological indices were remained unchanged compared to control. A large number of glomerular fibrin thrombi with entrapped red blood cells and simplified tubular epithelium in dilated and ectatic tubules were observed in high power field (×100) four hours after envenomation, which reduced significantly one week later. In our scintigraphic study, there was a statistically significant difference (P<0.05) in kidney count rate per pixels (CRPP) in both acute and chronic phases compared to the sham group that received normal saline (0.84±0.05 and 1.36±0.07 versus 1.7±0.05). CONCLUSION: The results of this preliminary animal study suggest renal scintigraphy is a non-invasive method to predict the occurrence of the AKI in H. lepturus envenomation. It leads the way for more investigation to counteract the renal failure induced by this venom.

Comparison of 99mTc-DMSA renal scintigraphy with biochemical and histopathological findings in animal models of acute kidney injury.

Biochemical and histological assays are currently used for the diagnosis and characterization of kidney injury. The purpose of this study was to compare technetium-99m-labeled dimercaptosuccinic acid (99mTc-DMSA) renal scintigraphy, as a non-invasive method, with common biochemical and histopathological methods in two animal models of acute kidney injury. Nephrotoxicity was induced either by gentamicin (100 mg/kg/day for one week) or unilateral ureteral ligation (UUO). Renal scintigraphy was performed 1 h after intravenous injection of 99mTc-DMSA (3 mCi). Furthermore, plasma levels of blood urea nitrogen (BUN), creatinine, sodium, and potassium were determined using an autoanalyzer. At the end of experiments, kidneys were excised for the measurement of activity uptake (mCi/gr) using a dose calibrator as well as histopathological examinations with hematoxylin and eosin (H&E) staining. There was a significant decrease in 99mTc-DMSA uptake in both gentamicin (P value = 0.049) and UUO (P value = 0.034) groups, and it was more significant in the former. The levels of BUN and creatinine increased in both gentamicin and UUO groups, while the levels of sodium and potassium remained unchanged. Furthermore, a strong correlation was found between DMSA uptake and histopathological findings. Scintigraphy with 99mTc-DMSA is capable of detection of kidney injury in both gentamicin and UUO groups. Moreover, a significant correlation was found between scintigraphy parameters and histopathological findings. This suggests 99mTc-DMSA as a non-invasive method for the evaluation of kidney injury induced by drugs or anatomical disorders.

Implementation of absolute quantification in small-animal SPECT imaging: Phantom and animal studies.

PURPOSE: Presence of photon attenuation severely challenges quantitative accuracy in single-photon emission computed tomography (SPECT) imaging. Subsequently, various attenuation correction methods have been developed to compensate for this degradation. The present study aims to implement an attenuation correction method and then to evaluate quantification accuracy of attenuation correction in small-animal SPECT imaging. METHODS: Images were reconstructed using an iterative reconstruction method based on the maximum-likelihood expectation maximization (MLEM) algorithm including resolution recovery. This was implemented in our designed dedicated small-animal SPECT (HiReSPECT) system. For accurate quantification, the voxel values were converted to activity concentration via a calculated calibration factor. An attenuation correction algorithm was developed based on the first-order Chang's method. Both phantom study and experimental measurements with four rats were used in order to validate the proposed method. RESULTS: The phantom experiments showed that the error of -15.5% in the estimation of activity concentration in a uniform region was reduced to +5.1% when attenuation correction was applied. For in vivo studies, the average quantitative error of -22.8 ± 6.3% (ranging from -31.2% to -14.8%) in the uncorrected images was reduced to +3.5 ± 6.7% (ranging from -6.7 to +9.8%) after applying attenuation correction. CONCLUSION: The results indicate that the proposed attenuation correction algorithm based on the first-order Chang's method, as implemented in our dedicated small-animal SPECT system, significantly improves accuracy of the quantitative analysis as well as the absolute quantification.

Review of biomedical Cerenkov luminescence imaging applications.

Cerenkov radiation is a fascinating optical signal, which has been exploited for unique diagnostic biological sensing and imaging, with significantly expanded use just in the last half decade. Cerenkov Luminescence Imaging (CLI) has desirable capabilities for niche applications, using specially designed measurement systems that report on radiation distributions, radiotracer and nanoparticle concentrations, and are directly applied to procedures such as medicine assessment, endoscopy, surgery, quality assurance and dosimetry. When compared to the other imaging tools such as PET and SPECT, CLI can have the key advantage of lower cost, higher throughput and lower imaging time. CLI can also provide imaging and dosimetry information from both radioisotopes and linear accelerator irradiation. The relatively short range of optical photon transport in tissue means that direct Cerenkov luminescence imaging is restricted to small animals or near surface human use. Use of Cerenkov-excitation for additional molecular probes, is now emerging as a key tool for biosensing or radiosensitization. This review evaluates these new improvements in CLI for both medical value and biological insight.

The Effect of Electromagnetic Field Generated by a Mobile Phone on the Performance of a SPECT Scanner: A Quantitative Study.

PURPOSE: The aim of the current attempt was quantitative investigation of the electromagnetic interference (EMI) of a mobile phone with the function of a SPECT gamma camera during data acquisition. MATERIALS AND METHODS: We tested the effect of a mobile phone, in both ringing mode and standby mode, on one SPECT gamma camera during scanning a cylindrical phantom containing 5.4 mCi (99m)Tc. The experiment was performed for different distances of 10, 12, 14, 16, 18, 20, 25, and 30 cm between mobile phone and head of the scanner, and for different head angles of 0, 30, 60, 90, 120, 150, and 180 degrees. A RF-EMF meter measured strength of electromagnetic field throughout the study. Statistically significant decrease in count number was considered to be electromagnetic interference. RESULTS: There was significant reduction in the recorded counts during ringing of the mobile phone in all studied distances. For gamma camera, fixed at a distance, there was no uniform pattern of reduction of the counts at different angles between two operation modes of the mobile phone. CONCLUSIONS: A mobile phone, at close distance, can be a sensible source of electromagnetic field, disturbing the normal function of a gamma camera.