9.4 T static magnetic field ameliorates imatinib mesylate-induced toxicity and depression in mice.

PURPOSE: 9.4 T magnetic resonance imaging (MRI) has been initially tested on healthy human volunteers, but its future application will benefit more from experiments with animal disease models. In the meantime, high static magnetic fields (SMFs) have been shown to improve mice mental health and have anti-tumor potentials. METHODS: We compared the anti-tumor effects of 9.4 T SMF with or without a commonly used chemotherapy drug imatinib mesylate on BALB/c (Nu/Nu) mice bearing gastrointestinal stromal tumor GIST-T1 cells. The body weight, food/water consumption, complete blood count, blood biochemistry, tumor weight, HE and Ki67 stains were examined. Locomotor activity and cognitive functions were also measured by four behavior tests, including open field, elevated plus maze, three-chamber and tail suspension tests. RESULTS: We found that the tumor growth was inhibited up to 62.88% when treated with 9.4 T SMF alone for 200 h. More importantly, 9.4 T SMF combined with 20 mg/kg imatinib mesylate can result in 92.75% tumor suppression, which is close to the anti-tumor effect of high dose (80 mg/kg) imatinib. However, 80 mg/kg imatinib caused severe side effects, including significantly reduced gain of body weight, abnormal liver function and depressive behaviors in mice. In contrast, 9.4 T SMF treatment significantly reduced these side effects, especially for the depressive behaviors. CONCLUSION: Our results demonstrate that 9.4 T SMF not only has anti-tumor effects on its own, but also could improve the anti-tumor effect of imatinib mesylate, reduce its toxicity and improve the mice mental health, which unraveled the great clinical potentials of high SMF in future applications.

Static Magnetic Fields Protect against Cisplatin-Induced Kidney Toxicity.

Cisplatin is one of the most widely used anti-cancer drugs that can effectively inhibit the growth of multiple types of cancer. However, its clinical application is limited by its severe side effects, especially kidney toxicity, caused by cisplatin-induced oxidative stress, inflammation and kidney cell apoptosis. Here, we found that moderate (a few hundred mT) quasi-uniform static magnetic fields (SMFs) could inhibit cisplatin-induced renal proximal tubular cell death, especially the vertically downward direction SMF. RNA-seq experiments demonstrate that SMFs induced differential gene expressions that are closely associated with oxidative stress, apoptosis, cytokine production, transmembrane transport and DNA repair. In vivo experiments show that SMFs can reduce cisplatin-induced kidney injury in cisplatin-administrated tumor-bearing mice by reducing oxidative stress, inflammation and cell apoptosis. Furthermore, high-dose cisplatin-induced acute nephrotoxicity can be effectively alleviated by SMF treatment of as little as one day, which significantly reduced the reactive oxygen species levels in kidneys and prolonged the mice's survival. Moreover, the concentration of cisplatin in the kidney was significantly attenuated in SMF-treated mice. Therefore, our study demonstrates the effects of moderate SMFs as a novel physical method to reduce oxidative stress, and revealed their future potential to be used against cisplatin-induced kidney toxicity in cancer treatment.

A Static Magnetic Field Improves Iron Metabolism and Prevents High-Fat-Diet/Streptozocin-Induced Diabetes.

Type 2 diabetes (T2D) is a metabolic disorder with high prevalence and severe complications that has recently been indicated to be treatable by a combined static magnetic field (SMF) and electric field. We systematically compared four types of SMFs and found that a downward SMF of ∼100 mT could effectively reduce the development of hyperglycemia, fatty liver, weight gain, and tissue injury in high-fat-diet (HFD)/streptozocin-induced T2D mice, but not the upward SMF. The downward SMF markedly restored the Bacteroidetes population and reversed the iron complex outer membrane receptor gene reduction in the mice gut microbiota, and reduced iron deposition in the pancreas. SMF also reduced the labile iron and reactive oxygen species level in pancreatic Min6 cells in vitro and prevented palmitate-induced Min6 cell number reduction. Therefore, this simple SMF setting could partially prevent HFD-induced T2D development and ameliorate related symptoms, which could provide a low-cost and non-invasive physical method to prevent and/or treat T2D in the future.

Circ_0000144 facilitates the progression of thyroid cancer via the miR-217/AKT3 pathway.

BACKGROUND: Thyroid carcinoma (TC) is the most common malignancy of the endocrine system. Circular RNA (circRNA) is vital in the regulation of tumor progression. Circ_0000144 serves as a novel oncogenic circRNA, and miR-217 is reported to inhibit the malignant phenotypes of cancer cells by targeting AKT3 in TC. The present study aimed to explore the regulatory mechanism of circ_0000144 and miR-217 in the progression of TC. METHODS: Circ_0000144 expression in 32 pairs of TC tissues and different TC cell lines (including BCPAP, K1, H7H83, and TPC-1) was detected by employing a quantitative real-time polymerase chain reaction (qRT-PCR). Circ_0000144 small interfering RNA was used to establish loss-of-function models. Cell counting kit-8 (CCK-8), BrdU (5-bromo-2'-deoxyuridine) and transwell assays were utilized to verify the effects of circ_0000144 on TC cell proliferation, migration and invasion, respectively. Bioinformatics, western blotting, a luciferase reporter experiment and qRT-PCR were employed to confirm the relationships among circ_0000144, miR-217 and AKT3. RESULTS: Circ_0000144 expression was remarkably elevated in TC tissues (p < 0.001) and TC cell lines. The elevation of circ_0000144 expression was markedly linked to tumor size (p = 0.015), TNM stage (p = 0.025) and lymph node metastasis (p = 0.017) of the patients. Functional studies showed that knocking down circ_0000144 repressed the malignancy of TC cells. Furthermore, miR-217 was identified as a downstream target of circ_0000144; inhibition of miR-217 could reverse the effects induced by circ_0000144 knockdown. Moreover, circ_0000144 could regulate AKT3 expression by suppressing miR-217 expression. CONCLUSIONS: Circ_0000144 exerts a cancer-promoting effect on TC cells via the miR-217/AKT3 pathway.

Positron Emission Tomography Imaging of Lesions pH Using 11C-Labeled Bicarbonate.

OBJECTIVES: As acid-base imbalance is involved in many pathological processes, the capability to image tissue pH alterations in the clinic could offer new ways to detect disease and respond to treatment. In this study, the authors show that tissue pH can be imaged in vivo with 11C-labeled bicarbonate (H11CO3-) buffer and positron emission tomography (PET). METHODS: H11CO3- was produced by on-column NaOH adsorption. Biodistribution of H11CO3- in normal mice was determined. In addition, uptake studies and inhibition experiments of H11CO3- in the S180 fibrosarcoma-bearing mice and the inflammatory mice were investigated with PET imaging. The tumor and inflammatory interstitial pH was measured by a needle pH microelectrode. RESULTS: PET imaging demonstrated the high uptake of H11CO3- in mice tumor tissues and inflammatory tissues, which showed that the average tumor or inflammatory interstitial pH was significantly lower than the surrounding tissue. Administration of sodium bicarbonate in the drinking water increased the measured tumor pH, while the uptake of H11CO3- in mice model tissues had no change. Similarly, administration with ammonium chloride (NH4Cl) decreased the pH, whereas the unchanged uptake of H11CO3- in mice model tissues was also found. However, after administration of acetazolamide, the low uptake of H11CO3- in mice model tissues was observed. CONCLUSIONS: H11CO3- solution is an endogenous bicarbonate buffer tracer that can be injected into patients without toxicity. H11CO3- PET can be used clinically to image pathological processes that are associated with acid-base imbalance, such as cancer and inflammation.

Cell penetrating peptide of sodium-iodide symporter effect on the I-131 radiotherapy on thyroid cancer.

The aim of the present study was to clarify whether the cell penetrating peptide of sodium-iodide symporter (NIS) has an effect on the I-131 radiotherapy of thyroid cancer. Firstly, we combined the HIV-1 TAT peptide (a cell penetrating peptide, dTAT) and established a nanoparticle vector (dTAT NP) to study the delivery efficiency of this cell-penetrating strategy for tumor-targeted gene delivery. dTAT NP was transfected into cultured TPC-1 cells as a model to study the effects of I-131 radiotherapy on thyroid cancer. Reverse transcription-quantitative polymerase chain reaction and western blotting results showed that the mRNA and protein expression levels of NIS in the transfected TPC-1 cells were substantially higher than in the negative control cells. MTT and flow cytometric analyses demonstrated that the cell growth and apoptosis rates of the TPC-1 cells were significantly inhibited and activated, respectively, by treatment with dTAT NP. The results of DAPI staining showed that treatment with dTAT NP visibly increased the nuclear apoptosis rate of the TPC-1 cells. The effect of dTAT NP on TPC-1 cells was associated with the promotion of caspase-3 and downregulation of the PI3K/Akt signaling pathway. In summary, the present data provide a pre-clinical proof-of-concept for a novel gene delivery system that efficiently delivers NIS to the targeted cancer cells and presents a satisfactory efficacy. This approach may offer an effective strategy for improving thyroid cancer gene therapy.

[A Treatment Plan Dose Interpolation Algorithm Based on Gradient Feature in Intensity-modulated Radiation Therapy].

The dose data produced by treatment plan system(TPS)in intensity-modulated radiation therapy(IMRT)has many gradient edge points.Considering this feature we proposed a new interpolation algorithm called treatment plan dose interpolation algorithm based on gradient feature in intensity-modulated radiation therapy(TDAGI),which improves the Canny algorithm to detect the gradient edge points and non-edge points by using the gradient information in the dose data plane.For each gradient edge point,the corresponding gradient profile was traced and the profile's sharpness was calculated,and for each non-edge point,the dispersion was calculated.With the sharpness or dispersion,the kernel coefficients of bi-cubic interpolation can be obtained and can be used as the central point to complete the bi-cubic interpolation calculation.Compared with bi-cubic interpolation and bilinear interpolation,the TDAGI algorithm is more accurate.Furthermore,the TDAGI algorithm has the advantage of gradient keeping.Therefore,TDAGI can be used as an alternative method in the dose interpolation of TPS in IMRT.

[In vivo and in vitro stability of ¹³¹I-Herceptin and its form of existence in the blood of rabbits].

OBJECTIVE: To evaluate the in vivo and in vitro stability of (131)I-Herceptin and its form of existence in the blood. METHODS: Herceptin was labelled with iodine-131 using the Iodogen method. (131)I-Herceptin was stored at 4 degrees celsius for 3, 24, 48, 72 and 96 h, and the radiochemical purity (RCP) was measured by high performance liquid chromatography (HPLC). Five rabbits received injections of (131)I-Herceptin and at 1, 3, 6, 24, 48, 72, 96 and 120 h after the injection, blood samples were taken to measure the RCP of (131)I-Herceptin in the serum, and the radio count of the serum and blood cells was calculated. RESULTS: The baseline RCP of (131)I-Herceptin was (94.9±2.7)%. The RCP was stable after placement at 4 degrees celsius for not over 72 h (F=15.985, P<0.001), but was significantly lowered to (82.6±2.8)% after preservation for over 72 h (t=9.971, P<0.001). Within the time of 1.0 to 96 h after injection in rabbits, (131)I-Herceptin existed mainly in the serum with a radio count of 81%-87%; 24 h after the injection, the RCP of (131)I-Herceptin in the serum was significantly lowered to (75.4±3.9)% (t=6.564, P<0.001). CONCLUSION: Storage at 4 degrees celsius for no more than 72 h does not obviously affect the activity of (131)I-Herceptin in terms of RCP. After injection in rabbits, (131)I-Herceptin exists mainly in the serum and its radiochemical purity remains stable within 24 h, after which obvious degradation occurs.

[Mechanism of cardiotoxicity associated with Herceptin using (131)I-Herceptin radioimmunoimaging].

OBJECTIVE: To study the mechanism of cardiotoxicity associated with Herceptin. METHODS: Herceptin was labeled with iodine-131 using the Iodogen method. Radioimmunoimaging was performed in 5 rabbits at 3 h to 5 days following (131)I-Herceptin injection to investigate the biodistribution of Herceptin. (131)I-Herceptin uptake in each organ or tissue relative to that in the muscular tissue (O/M ratio) was calculated and compared. On the fifth day following the injection, the organs including the heart, lung, liver and muscles were taken for measurement of the weight and radiocounts. HER2 expression was measured by immunohistochemistry in these organs and tissues. RESULTS: The O/M ratio of the heart was significantly higher than that of the lung (P=0.032) and liver (P=0.019) at 3 h after Herceptin injection, but reduced significantly at 24 h (P=0.001). The uptake of (131)I-Herceptin in the myocardium was slightly higher that that in the muscle and intestine, but lower than that in the lung and spleen. HER2 expression showed no significant difference between the myocardium and the other tissues such as the liver, lung, and kidney (H=3.236, P=0.172). CONCLUSION: Myocardium expresses low levels of HER2 and accumulates Herceptin no more than the other tissues.

[Relationship between fluorodeoxyglucose uptake and vascular endothelial growth factor in early-stage nasophygeal carcinoma].

OBJECTIVE: To study the overexpression of vascular endothelial growth factor (VEGF) and fluorine-18 fluorodeoxyglucose (FDG) uptake in early-stage nasopharyngeal carcinoma (NPC) and evaluate their relationship. METHODS: FDG positron emission tomography (PET) was performed in forty patients with stage I and stage II NPC. The maximum and mean standard uptake values (SUVmax and SUVmean, respectively) were measured in each patient, and the expression of VEGF was measured on paraffin sections using immunohistochemistry. RESULTS: The FDG uptake in the patients were 9.45-/+1.87 (SUVmax) and 6.04-/+1.09 (SUVmean), 8.95-/+1.91 (SUVmax) and 6.04-/+1.09 (SUVmean) in stage I patients, and 11.55-/+1.70 (SUVmax) and 7.98-/+1.1 (SUVmean) in stage II patients. The FDG uptake of stage II patients was higher than that of stage I patients. The FDG uptake of non-keratinizing differentiated carcinoma was 9.74-/+1.82 (SUVmax) and 6.82-/+1.23 (SUVmean) and 10.44-/+2.16 (SUVmax) and 6.68-/+1.35 (SUVmean) in non-keratinizing undifferentiated carcinoma, showing no significant differences between them (SUVmax: t=1.230, P>0.05; SUVmean: t=0.346, P>0.05). The VEGF-positive cells were 60.80% in the tumor. A correlation between VEGF expression and FDG uptake in he tumor was noted (r=0.460, P=0.03). CONCLUSION: VEGF overexpression is correlated to FDG uptake in patients with early-stage NPC. The SUV value reflects the glucose metabolism of NPC, and also shows the degree of oxygen insufficiency in the tumor tissue.

[Analysis of radioactive distribution in the sacrum in whole-body bone scanning].

OBJECTIVE: To analyze the radiogenic distribution in the sacrum in whole-body bone scanning. METHODS: A total of 212 patients receiving whole-body bone scanning without any explicit bone metastases were divided into different age and gender groups. The radioactive distribution in the sacrum in whole-body bone scanning was analyzed statistically. RESULTS: Of these cases, 31.1% presented with thin radioactive distribution in the sacrum and 11.3% exhibited increased radioactive distribution. Normal radioactive distribution in the sacrum was found in 57.6% of the cases. In both male and female elderly patients (>70 years), the rate of normal radioactive distribution in the sacrum was obviously reduced with increased rate of thin radioactive distribution. The female elderly patients showed higher rate of increased radioactive distribution in the sacrum than male elderly patients. CONCLUSION: The radioactive distribution in the sacrum is similar between female and male patients. Elderly male patients over 70 years have generally thin radioactive distribution in the sacrum due to the presence of osteoporosis, which is also associated with latent fracture of the sacrum to result in increased radioactive distribution in the sacrum in whole-body bone scanning.

[Effects of interferon-gamma on Her-2/neu expression and antitumor activity of 131I-Herceptin in breast cancer cell lines].

BACKGROUND & OBJECTIVE: Herceptin plays an important role in treating metastatic breast cancer by targeting Her2/neu, therefore, combining Herceptin with iodine-131 (131I) might enhance its antitumor activity. This study was to up-regulate Her2/neu expression by interferon-gamma (IFN-gamma), and explore its effect on binding and antitumor activity of 131I-Herceptin in breast cancer cell lines MCF-7, SKBR-3 and BT-474. METHODS: MCF-7, SKBR-3 and BT-474 cells were cultured with or without IFN-gamma (500 U/ml) for 48 h. The positive rate and mean fluorescence intensity (MFI) of Her2/neu on the 3 cell lines were tested by flow cytometry. Herceptin was labeled with 131I by Iodogen method, and its radiochemical purity (RCP) was tested by size-exclusion high-pressure liquid chromatography (HPLC). The binding rate of 131I-Herceptin on cells was measured by non-competitive saturation analysis, and its killing effect was estimated by colony-forming assay. The positive rate and MFI of Her2/neu, binding rate of 131I-Herceptin, and colony-forming rate were compared between IFN-gamma-induced group and control group by t test. RESULTS: For MCF-7 cells, the positive rate and MFI of Her2/neu were significantly higher in IFN-gamma-induced cells than in control cells [(15.2+/-4.7)% vs. (8.5+/-1.9)%, t=3.515, P<0.05; 121+/-17 vs. 38+/-7, t=7.823, P<0.002]; for SKBR-3 and BT-474 cells, no obvious difference of Her2/neu positive rate was observed between IFN-gamma-induced cells and control cells [(99.7+/-0.9)% vs. (98.9+/-1.1)%, P>0.05; (99.5+/-1.2)% vs. (98.1+/-0.9)%, P>0.05], but the MFI of Her2/neu was significantly higher in IFN-gamma-induced cells than in control cells (1,608+/-201 vs. 952+/-125, t=4.802, P<0.01; 1,968+/-192 vs. 1,020+/-98, t=7.614, P<0.002). The binding rates of Her2/neu were increased from (5.2+/-1.4)% to (12.3+/-3.4)% by 2.4 folds in MCF-7 cells, from (35.8+/-4.5)% to (48.9+/-7.1)% by 1.4 folds in SKBR-3 cells, and from (37.2+/-3.6)% to (59.5+/-8.7)% by 1.6 folds in BT-474 cells after inducement with IFN-gamma. The colony-forming rates were significantly lower in IFN-gamma-induced MCF-7, SKBR-3 and BT-474 cells than in control cells [(30+/-4)% vs. (49+/-3)%, t=6.574, P<0.05; (23+/-5)% vs. (37+/-6)%, t=3.105, P<0.05; (19+/-6)% vs. (34+/-5)%, t=3.323, P<0.05]. CONCLUSION: IFN-gamma can up-regulate Her-2/neu expression and increase the binding of 131I-Herceptin, hence, improve the inhibitory effect of 131I-Herceptin on proliferation of breast cancer cells.

[Preparation, quality control and biodistribution of 131I-herceptin in New Zealand rabbits].

OBJECTIVE: To study the immunoactivity,biodistribution and metabolic pattern of (131)I-Herceptin in rabbits. METHODS: Herceptin was radiolabelled with (131)I and its radiochemicalpurity (RCP) measured by size-exclusion high-pressure liquid chromatography (HPLC). The binding rate to BT-474 cells was measured to evaluate the immunoactivity of (131)I-Herceptin. (131)I-herceptin (2.0 mCi/kg) was injected intravenously into New Zealand rabbits. Scintigraphy on emission computed tomography was performed at 3 h, 1, 3 and 5 days after injection, and the radiocounts of the heart, liver and kidney etc. were compared with that of the muscle to calculate the organ-to-muscle activity ratio (O/M). On the fifth day,the rabbits were killed and the blood, myocardium, lung and other organs were obtained for measuring the radiocounts on gamma-counter to calculate the uptake percentage per gram tissue (ID%/g). RESULTS: The labeling rate of (131)I-herceptin was 93% with RCP of 95% and binding rate to BT-474 cells of 36.9%. After injection of (131)I-herceptin, the heart, lung and liver displayed dense radioactive regions but not the muscles and intestines. Three hours after injection, the O/M ratio of the heart was significantly higher than that of the lung, kidney and intestine (P<0.05), but decreased significantly one day after injection (t=10.817, P<0.001) with further decrement on days 3 and 5 (P<0.05). The O/M ratio of liver on day 1, 3, and 5 reduced significantly in comparison with that at 3 h (P<0.05). The uptake percentage was higher in the blood (11.3 ID/g%) than in the liver (2.8 ID/g%) and the myocardium (1.8 ID/g%). CONCLUSIONS: (131)I-herceptin possesses high immunoactivity which distributes mainly in the blood, liver and kidney, but with low uptake in the myocardium.

[Killing effect of sequential Herceptin and adriamycin treatment on breast cancer cell line in vitro].

OBJECTIVE: To observe the killing effect of Herceptin and adriamycin sequentially applied on breast cancer cell line in vitro. METHODS: BT-474 human breast cancer cells in exponential growth phase were treated with Herceptin alone, adriamycin alone and their sequential administration (Herceptin before adriamycin and vice versa), respectively. Under optical microscope, the morphological changes of the cells were observed before and after drug administration. The expression rate and mean fluorescence intensity (MFI) of HER-2/neu and cell death rate were detected by flow cytometry. RESULTS: Microscopically, the cells treated with different protocols all exhibited such changes as darkening and increase of cellular debris with irregular cell morphology. Flow cytometry revealed no significant difference in the expression rate of HER-2/neu in each group before and after treatment, but the MFI of HER-2/neu and death rate of the treated cells were significant different from those of the control group (P<0.05). The cell death rate of Herceptin-pretreated cells was significantly higher than that of adriamycin-pretreated ones (P<0.05). CONCLUSION: Herceptin pretreatment enhances the killing effect of adriamycin on breast cancer cell line BT-474, which provides experimental evidence for designing clinical sequential biochemotherapy of breast cancer.

[Diagnostic value of 99mTc-MIBI brain SPECT for brain glioma].

OBJECTIVE: To evaluate the value of (99m)Tc-MIBI brain single-photon emission computerized tomography (SPECT) in diagnosis of glioma. METHODS: Fifty-nine patients with glioma, 6 with brain abscess and 9 healthy controls underwent (99m)Tc-MIBI brain SPECT, and the diagnostic indices such as the sensitivity, specificity and accuracy were calculated. The tumor to non-tumor (T/NT) ratios were calculated according to the region of interest (ROI) and compared between the glioma group, healthy control group and brain abscess group by t test. RESULTS: Among the 59 cases of glioma, 51 showed positive results in (99m)Tc-MIBI SPECT, along with one of the healthy controls and 4 of brain abscess patients. The sensitivity, specificity and accuracy of the diagnosis were 86.4%, 66.7% and 82.4%, respectively. The T/NT ratio of brain glioma group was 2.6+/-1.2, significantly higher than that of normal group (t=3.6199, P<0.001) and brain abscess group (t=2.1327, P<0.05). CONCLUSION: (99m)Tc-MIBI brain SPECT is sensitive for diagnosis of brain glioma, and can distinguish malignant from benign lesions effectively.

[Therapeutic effects of strontium-89 against osseous metastases of lung cancer: analysis of 126 cases].

OBJECTIVE: To investigate the therapeutic effects of strontium-89 against osseous metastases of lung cancer. METHODS: A total of 126 patients with osseous metastases of lung cancer received strontium-89 treatment ((89)SrCl(2)) at the dose of 148 MBq given through a single intravenous injection. The analgesic effect was evaluated by the changes in the degree, frequency and scores of the pain, and the therapeutic effect assessed by observing the changes in the number and volume of osseous lesions after therapy and compared between different pathological types of lung cancer by Ka-square test. RESULTS: Within 6 months after the injection, the total pain relief rate was 70.6% (89/126), including 25 (19.8%) cases with pain vanished, suggesting significant alleviation of the pain intensity by the treatment (u=5.361, P<0.01). The frequency of pain was reduced in 78.6% (99/126) of the cases (u=4.589, P<0.01), and the average score of pain decreased significantly from 7.54+/-3.29 to 4.19+/-4.38 (t=6.865, P<0.001). The number and size of lesions decreased by more than 25% in 57 cases, showing a total efficacy rate of 45.2% (57/126). No significant difference was noted in the therapeutic effects among the 4 pathological types of lung cancer (P>0.05). CONCLUSIONS: Strontium-89 is effective for pain relief and tumor focus confinement in osseous metastases of lung cancer. No significant difference has been found in its effect between 4 different pathological types of lung cancer.

[Diagnosis of osseous metastases of malignant tumors by bone scanning combined with bone alkaline phosphatase detection].

OBJECTIVE: To assess the diagnostic value of bone alkaline phosphatase (B-AKP) detection in diagnosis of osseous metastases of malignant tumors. METHODS: Bone scanning and B-AKP detection were performed in 106 patients with malignancies. According to the findings in bone imaging and clinical symptoms, the patients were divided into bone metastases group (BM) and non-bone metastases group (NBM), between whom B-AKP was compared by t test. According to the number of osseous lesions on bone imaging, the patients were graded and B-AKP was compared between the 4 grades. Correlation analysis was performed between B-AKP level and the number of osseous lesions. RESULTS: Among the 106 patients, bone scanning found osseous metastases in 68 patients. For diagnosing osseous metastases, the sensitivity, specificity, PPV and NPV of B-AKP detection were 89.7%, 52.6%, 77.2% and 74.0%, respectively. B-AKP was 28.4+/-14.8 microg/L in BM group and 12.8+/-7.6 microg/L in NBM group, showing significant difference (t=6.056, P<0.001). B-AKP was 13.9+/-6.8 microg/L, 17.2+/-9.4 microg/L, 23.8+/-10.4 microg/L and 49.5+/-17.6 microg/L in patients of grade 0, 1, 2, and 3, respectively, showing significant difference by comparisons between the grades (P<0.05) except for that between grades 0 and 1 (t=1.320, P>0.05) and between grades 1 and 2 (t=1.803, P>0.05). B-AKP was 19.6+/-4.2 microg/L in patients with single hot focus and 13.1+/-3.4 microg/L in patients with single cold focus (t=2.570, P<0.05). Correlation analysis showed that there was low-degree correlation between B-AKP level and the number of osseous lesions (r=0.751, P<0.01). CONCLUSIONS: B-AKP level detection and bone imaging yield consistent results. For diagnosis of osseous metastases in patients with malignant tumor, bone scanning is the primary choice but in cases of single hot lesions, B-AKP should be performed to prevent missed diagnosis; for false positive lesions, B-AKP should also be detected to prevent misdiagnosis.

[Evaluation for degree of malignancy and prognosis of patients with brain glioma using 99Tcm-MIBI brain SPECT].

BACKGROUND & OBJECTIVE: It is important and useful to evaluate the degree of malignancy for therapeutic scheme and prognosis evaluation. Traditional imaging methods such as CT and MRI play the important role in distinguishing glioma, but sometimes it was still difficult to diagnose accurately only having the aid of these anatomic information. Stereotaxic needle biopsy is an invasive method and indicates only local pathologic change, sometimes the error of sample collection will result in inaccurate grading. 18F-FDG PET can reflect the glucose metabolic rate of tumor directly and is thought as the most useful method, but the cost is too high so that it cannot be used widely at present. This study measured (99)Tc(m)-MIBI uptake in the patients with different pathological types using (99)Tc(m)-MIBI brain scan and evaluated the malignant degree of astrocytoma and its prognosis. METHODS: Fifty-two patients with glioma and 15 collators were retrospectively analyzed. (99)Tc(m)-MIBI was injected into each patient via elbow vein. SPECT was performed 20 min(early phase) and 2 h (delayed phase) after injection. (1)Diagnostic indices such as sensitivity, specificity, and accuracy were calculated. (2) The tumor to non-tumor ratios (T/N) were calculated according to ROI and compared between groups of different malignancy grading by t-test. (3) The survival time (by means of mean survival time, MST) after (99)Tc(m)-MIBI brain SPECT was follow-up surveyed. According to T/N ratios, the patients were divided into four groups. The MST was compared between four groups by t-test. RESULTS: (1) Among 52 cases of glioma, 44 showed positive and 2 collators showed false-positive on (99)Tc(m)-MIBI SPECT and the sensitivity, specificity, and accuracy were 84.6%, 86.7%, and 85.1%,respectively. (2) On early phase and delayed phase,when T/N ratio was compared, there was no significant difference between grade-I astrocytoma and grade-II astrocytoma (P >0.05), nor was between patients with ependymocytomas and patients with oligodendrogliomas (P >0.05). There was significantly different between every other two groups (P< 0.001),showing the higher the malignancy of astrocytoma,the more the T/N ratio. (3)Comparison of MST indicated that the more the T/N ratio, the shorter the MST. MST in group with T/NT ratio of 1.2-2.0 was significantly longer than that in group with T/NT ratio of 4.1-(t=5.412,P< 0.001) and that in group with T/N ratio of 3.1-4.0(t=4.418,P< 0.001). MST in group of 2.1-3.0 was significantly longer than that in group of 4.1-(t=3.382, 0.002< P< 0.005) and that in group of 3.1-4.0 (t=2.389,0.02< P< 0.05). MST showed no significant difference between the group of 1.2-2.0 and the group of 2.1-3.0 (t=1.691,P >0.05), nor did between the group of 3.1-4.0 and group of 4.1-(t=1.629,P >0.05). CONCLUSION: As a noninvasive technique, (99)Tc(m)-MIBI brain SPECT is effective to diagnose brain glioma and distinguish its malignancy degree. This method, by monitoring the T/N ratio closely, is useful to discriminate tumor viability and determine the prognosis of patients.

[Evaluation of therapeutic effects of strontium-89 on osseous metastases of prostate cancer by bone scanning and B-AKP measurement].

OBJECTIVE: To evaluate the therapeutic effects of strontium-89 on osseous metastases of prostate cancer by bone scanning and bone alkaline phosphatase (B-AKP) measurement. METHODS: One week before and within 6 months after strontium-89 therapy, bone scanning and B-AKP measurement were performed in 73 patients with bone metastases of prostate cancer. 1. According to the number of osseous lesions on bone imaging, the patients were divided into Grade 0, 1, 2 and 3, and the numbers of bone lesions before and after therapy were compared by t-test. 2. Tumor to non-tumor ratios(T/NT) before and after treatment were calculated and compared. 3. Changes in B-AKP before and after therapy were compared. RESULTS: 1. Among the 73 patients, bone scanning revealed 618 bone lesions, averaging 8.6 +/- 7.4 before treatment. The number decreased to 349, averaging 3.8 +/- 6.7 after treatment, which showed a significant reduction (t = 4.079, P < 0.01). 2. After therapy, T/NT of bone lesions decreased significantly (t = 7.907, P < 0.01) from 5.36 +/- 4.67 to 3.17 +/- 2.95. 3. B-AKP decreased significantly (t = 3.349, P < 0.002) from (28.4 +/- 14.8) microgram/L to (20.9 +/- 11.7) microgram/L. 4. By bone scanning combined with B-AKP measurement, 5 false positive cases and 6 false negative cases were corrected. CONCLUSION: There is certain complementarity between bone scanning and B-AKP measurement, and they should be used in a combined way to achieve accurate evaluation of the therapeutic effects of strontium-89.

Radiosensitivity of hepatocarcinoma cell line BEL-7402.

OBJECTIVE: To assess the radiosensitivity of human hepatocarcinoma cell line BEL-7402. METHODS: Human hepatocarcinoma cell line BEL-7402 was cultured in vitro and then subjected to exposure to 6 MV X-ray at the doses ranging from 0 to 10 Gy. The survival rate of the cells following the exposure was assessed by determining the colony-forming units during further cell culture 12 to 14 d after the exposure, and the parameters for the radiosensitivity calculated. RESULTS and CONCLUSION: The parameters of BEL-7402 cells (D0=1.6, Dq=1.3, n=2, 4, SF2=0.63+/-0.05 Gy) demonstrates a high sensitivity of the cells to radiation.