Sahar Mirpour

In vivo tracking of 111In-oxine labeled mesenchymal stem cells following infusion in patients with advanced cirrhosis

BACKGROUND Several animal and few human studies suggest the beneficial role of bone marrow mesenchymal stem cells (MSCs) in liver cirrhosis. However, little is known about the fate of MSCs after infusion in cirrhotic patients. We evaluated stem cell biodistribution after peripheral infusion of MSCs in four cirrhotic patients. METHODS After three passages of MSCs, the patients received a total of 250-400×10(6) cells, of which only 50% of the cells were labeled. Specific activities of 0.21-0.67 MBq/10(6) cells were maintained for the injected labeled MSCs. Planar whole-body acquisitions (anterior/posterior projections) were acquired immediately following infusion as well as at 2 h, 4 h, 6 h, 24 h, 48 h, 7th and 10th days after cell infusion. RESULTS After intravenous infusion, the radioactivity was first observed to accumulate in the lungs. During the following hours to days, the radioactivity gradually increased in the liver and spleen, with spleen uptake exceeding that in the liver in all patients. Region-of-interest analysis showed that the percentage of cells homing to the liver (following decay and background corrections and geometric mean calculation) increased from 0.0%-2.8% at immediately post-infusion images to 13.0-17.4% in 10th-day post-infusion. Similarly, the residual activities in the spleen increased from 2.0%-10.2% at immediately post-infusion images to 30.1%-42.2% in 10th-day post-infusion. During the same period, the residual activities in the lungs decreased from 27.0-33.5% to 2.0-5.4%. CONCLUSION The infusion of MSCs labeled with (111)In-oxine through a peripheral vein is safe in cirrhosis. Cell labeling with (111)In-oxine is a suitable method for tracking MSC distribution after infusion.

Cytotoxicity of 111In-oxine on mesenchymal stem cells: a time-dependent adverse effect.

BackgroundRadioactive labeling with 111indium (111In) tracers has been among the most widely used methods for tracking stem cells. As the first experiment on human stem cells, we designed a study to continuously follow the influence of 111In labeling on stem cell viability during the 2-week period of postlabeling. MethodsAfter culturing mesenchymal stem cells (MSCs), we divided the cells into six samples, each of which contained 1×106 MSCs. The first sample was considered as the control. The remaining five samples (samples 2–6) were labeled with the following doses of 111In-oxine, respectively: 0.76, 1.64, 3.48, 5.33, and 7.16 MBq/106 MSCs. To evaluate the effects of 111In-oxine labeling on cellular viability and count, all samples were examined immediately after labeling (2 h) as well as 24, 48 h, and 5, 7, and 14 days postlabeling. ResultsNo statistically significant relationship was found between labeling efficiency and administered dose. Associations between the specific activity and radiotracer dosage was significant (P=0.001, r=0.9). In addition, a negative correlation was noted between radiotracer dosage and viability during the 2-week period of follow-up. ConclusionCytotoxic effects of 111In on human stem cells is a time-dependent phenomenon and hence, assessment of the stem cell viability immediately after labeling (which is frequently made in clinical trials) is unable to detect adverse effects of this radiopharmaceutical on the integrity of stem cells. Even low doses of 111In-oxine are accompanied by significant cell loss in a 2-week period. Although it has been confirmed that nuclear medicine techniques are the most sensitive methods for stem cell tracking, we recommend that the application of this tracking technique should be treated with great reserve, and if necessary, as little of 111In-oxine as possible should be added to the cells (or only a limited portion of the cells should be labeled) to minimize cell death.

Evaluation of the profile of alopecia areata and the prevalence of thyroid function test abnormalities and serum autoantibodies in Iranian patients

BackgroundThe study aimed at evaluating the prevalence of thyroid function abnormalities in patients with alopecia areata (AA) and its association with other autoimmune diseases and various autoimmune antibodies.MethodWe retrospectively analyzed medical records of 123 patients with AA. The main site of involvement, pattern, and extent of alopecia as well as presence of the similar disease in first-degree family members and serologic status of patients were recorded.ResultsParticipating in the study were 57 males and 66 females (6 to 59 years old). In the majority of patients (69.9%) the disease was manifested in the first two decades of life. Patients with family members having alopecia were recorded in 24.4%. Thyroid function abnormalities were found in 8.9% of patients. Positive autoimmune antibodies were associated with AA in 51.4% of patients with no significant association between the severity and duration of disease and presence of these antibodies.ConclusionThe incidence of positive auto-immune antibodies in Iranian patients is higher than previous reports. Concerning the female:male ratio, thyroid function tests and the prevalence of alopecia in first-degree relatives, our results are compatible with previous data obtained from different ethnic populations. Previous reports documented that a greater severity and longer duration of AA were seen in the early onset forms; however our result are relatively different which could be explained by differences in genetic factors.

A Novel Inherently Radiopaque Bead for Transarterial Embolization to Treat Liver Cancer - A Pre-clinical Study

Purpose: Embolotherapy using microshperes is currently performed with soluble contrast to aid in visualization. However, administered payload visibility dimishes soon after delivery due to soluble contrast washout, leaving the radiolucent beads location unknown. The objective of our study was to characterize inherently radiopaque beads (RO Beads) in terms of physicomechanical properties, deliverability and imaging visibility in a rabbit VX2 liver tumor model. Materials and Methods: RO Beads, which are based on LC Bead® platform, were compared to LC Bead. Bead size (light microscopy), equilibrium water content (EWC), density, X-ray attenuation and iodine distribution (micro-CT), suspension (settling times), deliverability and in vitro penetration were investigated. Fifteen rabbits were embolized with either LC Bead or RO Beads + soluble contrast (iodixanol-320), or RO Beads+dextrose. Appearance was evaluated with fluoroscopy, X-ray single shot, cone-beam CT (CBCT). Results: Both bead types had a similar size distribution. RO Beads had lower EWC (60-72%) and higher density (1.21-1.36 g/cc) with a homogeneous iodine distribution within the beads interior. RO Beads suspension time was shorter than LC Bead, with durable suspension (>5 min) in 100% iodixanol. RO Beads ≤300 µm were deliverable through a 2.3-Fr microcatheter. Both bead types showed similar penetration. Soluble contrast could identify target and non-target embolization on fluoroscopy during administration. However, the imaging appearance vanished quickly for LC Bead as contrast washed-out. RO Beads+contrast significantly increased visibility on X-ray single shot compared to LC Bead+contrast in target and non-target arteries (P=0.0043). Similarly, RO beads demonstrated better visibility on CBCT in target arteries (P=0.0238) with a trend in non-target arteries (P=0.0519). RO Beads+dextrose were not sufficiently visible to monitor embolization using fluoroscopy. Conclusion: RO Beads provide better conspicuity to determine target and non-target embolization compared to LC Bead which may improve intra-procedural monitoring and post-procedural evaluation of transarterial embolization.

The Role of PET/CT in the Management of Cervical Cancer

OBJECTIVE. Cervical cancer is the second most common malignancy in women worldwide and the third most common cause of cancer mortality in the United States. The aim of this article is to describe cervical cancer and outline the value of (18)F-FDG PET/CT in the management of cervical malignancy. CONCLUSION. The value of PET/CT has been found in staging and treatment strategy for cervical cancer. FDG PET/CT facilitates decision-making and radiation treatment planning and provides important information about treatment response, disease recurrence, and long-term survival.

Utilizing the micron sized non-thermal atmospheric pressure plasma inside the animal body for the tumor treatment application.

This study aimed to evaluate the effects of micron sized non-thermal atmospheric pressure plasma inside the animal body on breast cancer tumor. The μ-plasma jet consists of micron sized hollow tube in which pure helium gas is ionized by high voltage (4 kV) and high frequency (6 kHz). The efficiency of the plasma treatment in killing cancer cells was first investigated by cell viability measurements of treated 4T1 cells using flow cytometry and cell cycle analysis. For exploration of the in vivo effects of the plasma treatment, the BALB/c mice inoculated by 4T1 cell lines were exposed subcutaneously to plasma for 3 minutes. In addition, H&E staining, TUNEL and Western blotting assays were performed in order to observed the effects of the non-thermal plasma on the tumor cells. The results showed that the efficiency of the plasma in suppression of the tumor growth is comparable to that of a typical chemotherapy drug. Moreover, the results indicated that the plasma induces apoptosis in the tumor tissue and increases the ratio of the apoptotic to anti-apoptotic protein expression. We believe that these findings presented herein may extend our knowledge of the mechanisms by which the plasma exerts its promising anti-cancer effects.

Quantitative Assessment of Dacryoscintigraphic Images in the Evaluation of Epiphora

Background: At the present time, only visual analysis is implemented on dacryoscintigraphic images and quantitative assessments are not routinely obtained. The authors have designed a novel, simple, quantitative method for the diagnosis of sac and post-sac obstructions based on the dacryoscintigraphic images. Method: Fifty-nine patients with severe unilateral epiphora were included and the contralateral asymptomatic eyes were used as controls. After ocular instillation of 0.1 cc isotonic saline containing 4 MBq 99mTcO4, dynamic images were obtained for 20 minutes. Visual interpretation was done by two blinded specialists in nuclear medicine. A Time-Activity Curve (TAC) was generated for each eye and its pattern was divided to plateau type, shallow-down sloping and deep-down sloping. The excretion ratio (expressed as the percentage of drained activity) in the 2nd, 3rd, 5th, 7th, 10th, 15th and 20th minute of the study was calculated based on the following formula: (the total count in the region of interest (ROI) in the 1st minute – the total ROI count in the 2nd, 3rd, 5th, 7th, 10th, 15th or 20th minute/the total ROI count in the 1st minute) × 100. The results of the quantitative analysis were compared with the clinical symptoms, visual analysis and TAC pattern. Results: At the optimal cut-off points for the 2nd, 3rd, 5th and 7th minute, the sensitivity of the prediction of obstruction was 76%, 72%, 71% and 69%, respectively. The correlation between visual interpretation and the TAC pattern was statistically significant. Conclusion: The quantitative evaluation of dacryoscintigraphic images would contribute greatly to achieving an easier and more objective interpretation of the scintigraphic results and also provides a reliable tool for inter-individual comparison and the follow-up of patients. As it is the first time that this innovative method has been examined clinically, it will be necessary to investigate its clinical utility in a larger series of patients.

The prevalence and significance of increased gastric wall radiotracer uptake in sestamibi myocardial perfusion SPECT

Background: Limited available data indicate that a specific pattern of increased gastric wall radiotracer uptake is associated with dyspepsia. Our purpose was to evaluate the frequency of this finding and its relation with dyspeptic evidences. Method: 1056 consecutive outpatients referred for myocardial perfusion SPECT were interviewed concerning the dyspeptic symptoms, current gastric medications and previous gastroduodenal interventions. The intensity of gastric wall activity was graded qualitatively as G1 or hyperactive gastric wall (equivalent to the patient’s heart activity) and G2 (less than heart activity). Results: The pattern of gastric wall hyperactivity was identified in 1.9% of patients. Dyspeptic symptoms were present in 80 and 18.6% of G1 and G2 patients, respectively (p<0.001). The dyspeptic symptoms were classified as ulcer-like in 37.5%, dysmotility-like in 43.75% and GERD-like in 18.75% of the dyspeptic G1 patients. Considering the classification of dyspepsia, there was no significant difference between the dyspeptic patients of groups. The history of previous gastroduodenal interventions and current use of gastric medications was significantly higher among G1 patients. Conclusion: The infrequent pattern of gastric wall hyperactivity could be clinically important and can identify a category of patients, who require additional diagnostic gastrointestinal investigation to specify another possible noncardiac origin of complaints.

Radio-iodine therapy and Helicobacter pylori infection

BackgroundHelicobacter pylori is the most important cause of gastritis and related morbidities. Following consumption, radioactive iodine accumulates considerably in the stomach. On the basis of this observation, we decided to determine whether the high radiation induced by radio-iodine in the stomach is effective in the eradication of this infection.MethodsAll consecutive patients with differentiated thyroid carcinoma, who were referred for radio-iodine therapy [dose 117.1 ± 24.4 mCi (4.3 ± 0.9 GBq), range 100–200 mCi (3.7–7.4 GBq)], were enrolled. To detect H. pylori infection, the urease breath test (UBT) was performed 1-2 h before radio-iodine consumption and the test was repeated 2 months later.ResultsOf 88 patients, 71 had pre-treatment positive UBT. Of these, 23 patients had negative post-treatment result, which means a significant reduction (26.1%, 95% CI 16.8–35.5%) in the number of positive UBT results in our treated population (32.4% of UBT-positive cases became UBT-negative).ConclusionsConsidering the high prevalence of reinfection in developing countries, the therapeutic benefit would have been more considerable if the second UBT had been done with a lag time of less than 2 months. Although radio-iodine therapy is not a logical method for the treatment of patients suffering from H. pylori, our finding provides indirect evidence about the radiosensitivity of bacteria, the future clinical applications of which need to be further evaluated. Also this finding can be useful for the food industry, where radiation is used widely to sterilize food. Regarding the possibility of H. pylori suppression, we recommend not using UBT for screening for the infection for at least within 2 months following radio-iodine therapy.

Preclinical Benefit of Hypoxia-Activated Intraarterial Therapy with Evofosfamide in Liver Cancer

Purpose: To evaluate safety and characterize anticancer efficacy of hepatic hypoxia-activated intra-arterial therapy (HAIAT) with evofosfamide in a rabbit model. Experimental Design: VX2-tumor-bearing rabbits were assigned to 4 intra-arterial therapy (IAT) groups (n = 7/group): (i) saline (control); (ii) evofosfamide (Evo); (iii) doxorubicin–lipiodol emulsion followed by embolization with 100–300 μm beads (conventional, cTACE); or (iv) cTACE and evofosfamide (cTACE + Evo). Blood samples were collected pre-IAT and 1, 2, 7, and 14 days post-IAT. A semiquantitative scoring system assessed hepatocellular damage. Tumor volumes were segmented on multidetector CT (baseline, 7/14 days post-IAT). Pathologic tumor necrosis was quantified using manual segmentation on whole-slide images. Hypoxic fraction (HF) and compartment (HC) were determined by pimonidazole staining. Tumor DNA damage, apoptosis, cell proliferation, endogenous hypoxia, and metabolism were quantified (γ-H2AX, Annexin V, caspase-3, Ki-67, HIF1α, VEGF, GAPDH, MCT4, and LDH). Results: cTACE + Evo showed a similar profile of liver enzymes elevation and pathologic scores compared with cTACE. Neither hematologic nor renal toxicity were observed. Animals treated with cTACE + Evo demonstrated smaller tumor volumes, lower tumor growth rates, and higher necrotic fractions compared with cTACE. cTACE + Evo resulted in a marked reduction in the HF and HC. Correlation was observed between decreases in HF or HC and tumor necrosis. cTACE + Evo promoted antitumor effects as evidenced by increased expression of γ-H2AX, apoptotic biomarkers, and decreased cell proliferation. Increased HIF1α/VEGF expression and tumor glycolysis supported HAIAT. Conclusions: HAIAT achieved a promising step towards the locoregional targeting of tumor hypoxia. The favorable toxicity profile and enhanced anticancer effects of evofosfamide in combination with cTACE pave the way towards clinical trials in patients with liver cancer. Clin Cancer Res; 23(2); 536–48. ©2016 AACR.