One-day examination of triple nuclear medicine imaging and application in evaluating transarterial embolization.

A diagnosis based on multiple nuclear medicine imaging (NMI) was more comprehensive in approaching the nature of pathological changes. In this research, a method to realize triple NMIs within one day was developed based on the reasonable arrangements of 68Ga-RGD PET/CT specialized on neovascularization, 99mTc-HL-91 SPECT/CT specialized on hypoxia and 18F-FDG PET/CT specialized on tumor metabolism. Feasibility was verified in evaluating the therapeutic effects of transarterial embolization (TAE) performed on rabbit models with VX2 tumor. Radiation dosimetry was carried out to record the radiation exposure from multiple injections of radiopharmaceuticals. In results, the one-day examination of triple NMIs manifested the diversity of the postoperative histological changes, including the local neovascularization induced by embolization, hypoxic state of embolized tissues, and suppression of tumor metabolism. More importantly, radiation dosage from radiopharmaceuticals was limited below 5.70 ± 0.90 mSv. In conclusion, the strong timeliness and complementarity of one-day examination of triple nuclear medicine imaging made it clinically operative and worthy of popularizing. There was flexibility in combining distinct NMIs according to the clinical demands, so as to provide comprehensive information for diagnosis.

Intense 18 F-PSMA-1007 Uptake of Splenic Hemangioma.

ABSTRACT: A 77-year-old man was referred for 18 F-PSMA-1007 PET/CT scan for initial staging of biopsy-proved prostate adenocarcinoma. 18 F-PSMA-1007 PET/CT showed focal intense 18 F-PSMA-1007 of the prostate adenocarcinoma and a focal intense activity (SUV max , 27) in the spleen. The 18 F-PSMA-1007-avid splenic lesion corresponded to a splenic hemangioma, which was initially detected on contrast-enhanced CT 7 months ago and unchanged in size and enhancement pattern on follow-up contrast-enhanced CT. This case indicates that splenic hemangioma should be included in the differential diagnosis of PSMA-avid splenic lesions.

Radioiodine-131-Labeled Theranostic Nanoparticles for Transarterial Radioembolization and Chemoembolization Combination Therapy of VX2 Liver Tumor.

In interventional treatment, materials are administered into the blood supply artery and directly delivered to tumors, offering proper scenarios for nanomedicine potential clinical applications. Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are effective treatment methods for hepatocellular carcinoma (HCC), but postoperative residual tumor may result in intrahepatic recurrence and distant metastasis. The combination therapy of TACE and TARE based on multifunctional nanoparticles (NPs) is expected to overcome the drug resistance in hypoxic tumors and improve the therapeutic effect. Herein, BaGdF5 NPs are synthesized and then coated with polydopamine (PDA), conjugated with the chemotherapeutic drug cis-diamminedichloride platinum (CDDP), radio-labeled with therapeutic radionuclide 131 I, yielding 131 I-BaGdF5 @PDA-CDDP NPs. The in vitro anti-cancer effects of 131 I-BaGdF5 @PDA-CDDP NPs are confirmed using CCK-8 and γ-H2AX assays in Huh7 cells. Mixed with Lipiodol, 131 I-BaGdF5 @PDA-CDDP NPs are injected into the hepatic artery via a microcatheter to realize the TACE and TARE combination therapy in a rabbit VX2 liver tumor model. The results indicate that glucose metabolism is clearly decreased based on 18 F-FDG PET imaging and the apoptosis of tumor cells is increased. Furthermore, 131 I and BaGdF5 NPs can be used for SPECT imaging and CT/MR imaging respectively, facilitating real-time monitoring of the in vivo biodistribution of 131 I-BaGdF5 @PDA-CDDP NPs.

Silk fibroin-based embolic agent for transhepatic artery embolization with multiple therapeutic potentials.

BACKGROUND: The excellent physicochemical and biomedical properties make silk fibroin (SF) suitable for the development of biomedical materials. In this research, the silk fibroin microspheres (SFMS) were customized in two size ranges, and then carried gold nanoparticles or doxorubicin to evaluate the performance of drug loading and releasing. Embolization efficiency was evaluated in rat caudal artery and rabbit auricular artery, and the in vivo distribution of iodinated SFMS (125I/131I-SFMS) after embolization of rat hepatic artery was dynamically recorded by SPECT. Transhepatic arterial radioembolization (TARE) with 131I-SFMS was performed on rat models with liver cancer. The whole procedure of selective internal radiation was recorded with SPECT/CT, and the therapeutic effects were evaluated with 18 F-FDG PET/CT. Lastly, the enzymatic degradation was recorded and followed with the evaluation of particle size on clearance of sub-micron silk fibroin. RESULTS: SFMS were of smooth surface and regular shape with pervasive pores on the surface and inside the microspheres, and of suitable size range for TAE. Drug-loading functionalized SFMS with chemotherapy or radio-sensitization, and the enhanced therapeutic effects were proved in treating HUH-7 cells as lasting doxorubicin release or more lethal radiation. For artery embolization, SFMS effectively blocked the blood supply; when 131I-SFMS serving as the embolic agent, the good labeling stability and embolization performance guaranteed the favorable therapeutic effects in treating in situ liver tumor. At the 5th day post TARE with 37 MBq/3 mg 131I-SFMS per mice, tumor activity was quickly inhibited to a comparable glucose metabolism level with surrounding normal liver. More importantly, for the fragments of biodegradable SFMS, smaller sized SF (< 800 nm) metabolized in gastrointestinal tract and excreted by the urinary system, while SF (> 800 nm) entered the liver within 72 h for further metabolism. CONCLUSION: The feasibility of SFMS as degradable TARE agent for liver cancer was primarily proved as providing multiple therapeutic potentials.

A multidomain fusion model of radiomics and deep learning to discriminate between PDAC and AIP based on 18F-FDG PET/CT images.

PURPOSE: To explore a multidomain fusion model of radiomics and deep learning features based on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) images to distinguish pancreatic ductal adenocarcinoma (PDAC) and autoimmune pancreatitis (AIP), which could effectively improve the accuracy of diseases diagnosis. MATERIALS AND METHODS: This retrospective study included 48 patients with AIP (mean age, 65 ± 12.0 years; range, 37-90 years) and 64 patients with PDAC patients (mean age, 66 ± 11.3 years; range, 32-88 years). Three different methods were discussed to identify PDAC and AIP based on 18F-FDG PET/CT images, including the radiomics model (RAD_model), the deep learning model (DL_model), and the multidomain fusion model (MF_model). We also compared the classification results of PET/CT, PET, and CT images in these three models. In addition, we explored the attributes of deep learning abstract features by analyzing the correlation between radiomics and deep learning features. Five-fold cross-validation was used to calculate receiver operating characteristic (ROC), area under the roc curve (AUC), accuracy (Acc), sensitivity (Sen), and specificity (Spe) to quantitatively evaluate the performance of different classification models. RESULTS: The experimental results showed that the multidomain fusion model had the best comprehensive performance compared with radiomics and deep learning models, and the AUC, accuracy, sensitivity, specificity were 96.4% (95% CI 95.4-97.3%), 90.1% (95% CI 88.7-91.5%), 87.5% (95% CI 84.3-90.6%), and 93.0% (95% CI 90.3-95.6%), respectively. And our study proved that the multimodal features of PET/CT were superior to using either PET or CT features alone. First-order features of radiomics provided valuable complementary information for the deep learning model. CONCLUSION: The preliminary results of this paper demonstrated that our proposed multidomain fusion model fully exploits the value of radiomics and deep learning features based on 18F-FDG PET/CT images, which provided competitive accuracy for the discrimination of PDAC and AIP.

The inhibiting effect of alpha-based TARE on embolized vessels and neovascularization.

Transarterial embolization (TAE) is a personalized technology that offers precise delivery of chemotherapeutic drugs or selective internal radiation therapy for hepatocellular carcinoma (HCC). Beta-emitting radionuclide embolisms for TAE (ß-based TARE) are commonly used in the clinic via inducing biochemical lethality on tumor cells, while alpha-emitting radionuclides-based embolisms for TAE (α-based TARE) are still under study. The feeding artery plays a key role in tumor growth, metastasis, and recurrence. In this research, the auricular central arteries (ACAs) of rabbits were embolized with silk fibroin-based microspheres (SFMs) or SFMs integrated with α (Ra-223) or ß (I-131) radionuclides to investigate the influence on vessels. TARE-induced tissue necrosis and the following neovascularization were measured by pathological analysis and 68Ga-DOTA-RGD PET/CT. The results showed that, compared to I-131, Ra-223 enhanced the growth inhibition of human hepatoma cells Huh-7 and induced more DNA double-strand breaks in vascular smooth muscle cells. Unlike ß-based TARE, which mainly led to extensive necrosis of surrounding tissues, α-based TARE induced irreversible necrosis of a limited area adjacent to the embolized vessels. RGD PET revealed the inhibition on neovascularization in α-based TARE (SUVmax = 0.053 ± 0.004) when compared with normal group (SUVmax = 0.099 ± 0.036), the SFMs-lipiodol group (SUVmax = 0.240 ± 0.040), and ß-based TARE (SUVmax = 0.141 ± 0.026), owing to the avoidance of the embolism-induced neovascularization. In conclusion, α-based TARE provided a promising strategy for HCC treatments via destroying the embolized vessels and inhibiting neovascularization.

Development of a novel radiofluorinated riboflavin probe for riboflavin receptor-targeting PET imaging.

Riboflavin receptor 3 (RFVT3) is a key protein in energetic metabolism reprogramming and is overexpressed in multiple cancers involved in malignant proliferation, angiogenesis, chemotherapy resistance, and immunosuppression. To enable non-invasive real-time quantification of RFVT3 in tumors, we sought to develop a suitable PET probe that would allow specific and selective RFVT3 imaging in vivo. A novel radiofluorinated riboflavin probe (18F-RFTA) based on riboflavin was synthesized and characterized in terms of radiochemical purity, hydrophilicity, binding affinity, and stability. Positron emission tomography (PET) imaging of 18F-RFTA was performed in U87MG tumor-bearing mice. Immunohistochemistry staining was carried out to determine the expression of RFVT3 in U87MG tumors. 18F-RFTA was characterized by high radiochemical purity and RFVT3 binding affinity, and remarkable stability in vitro and in vivo. Small-animal PET imaging with 18F-RFTA revealed significantly higher uptake in RFVT3-expressing U87MG tumors than in muscle. In conclusion, we have developed the first radiofluorinated riboflavin-based PET probe that is suitable for imaging RFVT3-positive tumors. The new target/probe system can be leveraged for extensive use in the diagnosis and treatment of RFVT3 overexpressing diseases, such as oncologic, cardiovascular, and neurodegenerative diseases.

Comparison of the diagnostic efficacy of 68 Ga-FAPI-04 PET/MR and 18F-FDG PET/CT in patients with pancreatic cancer.

PURPOSE: We sought to assess the performance of 68 Ga-FAPI-04 PET/MR for the diagnosis of primary tumours as well as metastatic lesions in patients with pancreatic cancer and to compare the results with those of 18F-FDG PET/CT. METHODS: Prospectively, we evaluated 33 patients suspected to have pancreatic adenocarcinoma, of whom thirty-two were confirmed by histopathology, and one had autoimmune pancreatitis confirmed by needle biopsy and glucocorticoid treatment. Within 1 week, each patient underwent both 68 Ga-FAPI-04 PET/MR and 18F-FDG PET/CT. Comparisons of the detection abilities for primary tumours, lymph nodes, and metastases were conducted for the two imaging approaches. The original maximum standard uptake values (SUVmax) and normalised SUVmax (SUVmax/SUVbkgd) of paired lesions on 68 Ga-FAPI-04 PET/MR and 18F-FDG PET/CT were measured and compared. RESULTS: Thirty pancreatic cancer patients and three pancreatitis patients were enrolled. 68 Ga-FAPI-04 PET/MR and 18F-FDG PET/CT exhibited equivalent (100%) detection rates for primary tumours. The original/normalised SUVmax of primary tumours on 68 Ga-FAPI-04 PET was markedly higher than that on 18F-FDG (p < 0.05). Sixteen pancreatic cancer patients had pancreatic parenchymal uptake, whereas 18F-FDG PET images showed parenchymal uptake in only four patients (53.33% vs. 13.33%, p < 0.001). 68 Ga-FAPI-04 PET detected more positive lymph nodes than 18F-FDG PET (42 vs. 30, p < 0.001), while 18F-FDG PET was able to detect more liver metastases than 68 Ga-FAPI-04 (181 vs. 104, p < 0.001). In addition, multisequence MR imaging helped explain ten pancreatic cancers that could not be definitively revealed due to 68 Ga-FAPI-04 inflammatory uptake and identified more liver metastases than 18F-FDG (256 vs. 181, p < 0.001). CONCLUSION: 68 Ga-FAPI-04 PET might be better than 18F-FDG PET in the detection of suspicious lymph node metastases. MR multiple sequence imaging of 68 Ga-FAPI-04 PET/MR was helpful for explaining pancreatic lesions in patients with obstructive inflammation and detecting tiny liver metastases.

Recent advances and applications of microspheres and nanoparticles in transarterial chemoembolization for hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is a recommended treatment for patients suffering from intermediate and advanced hepatocellular carcinoma (HCC). As compared to the conventional TACE, drug-eluting bead TACE demonstrates several advantages in terms of survival, treatment response, and adverse effects. The selection of embolic agents is critical to the success of TACE. Many studies have been performed on the modification of the structure, size, homogeneity, biocompatibility, and biodegradability of embolic agents. Continuing efforts are focused on efficient loading of versatile chemotherapeutics, controlled sizes for sufficient occlusion, real-time detection intra- and post-procedure, and multimodality imaging-guided precise treatment. Here, we summarize recent advances and applications of microspheres and nanoparticles in TACE for HCC. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Molecular Imaging of Tumor Microenvironment to Assess the Effects of Locoregional Treatment for Hepatocellular Carcinoma.

Liver cancer is one of the leading causes of cancer deaths worldwide. Among all primary liver cancers, hepatocellular carcinoma (HCC) is the most common type, representing 75%-85% of all primary liver cancer cases. Median survival following diagnosis of HCC is approximately 6 to 20 months due to late diagnosis in its course and few effective treatment options. Interventional therapy with minimal invasiveness is recognized as a promising treatment for HCC. However, due to the heterogeneity of HCC and the complexity of the tumor microenvironment, the long-term efficacy of treatment for HCC remains a challenge in the clinic. Tumor microenvironment, including factors such as hypoxia, angiogenesis, low extracellular pH, interstitial fluid pressure, aerobic glycolysis, and various immune responses, has emerged as a key contributor to tumor residual and progression after locoregional treatment for HCC. New approaches to noninvasively assess the treatment response and assist in the clinical decision-making process are therefore urgently needed. Molecular imaging tools enabling such an assessment may significantly advance clinical practice by allowing real-time optimization of treatment protocols for the individual patient. This review discusses recent advances in the application of molecular imaging technologies for noninvasively assessing changes occurring in the microenvironment of HCC after locoregional treatment.

The exploration of quantitative intra-tumoral metabolic heterogeneity in dual-time 18F-FDG PET/CT of pancreatic cancer.

PURPOSE: We aimed to analyze the change of quantitative intra-tumoral metabolic heterogeneity consisting of texture features and conventional metabolic parameters of pancreatic cancer (PC) in dual-time 2-deoxy-2(18F) fluoro-D-glucose (18F-FDG) positron emission tomography-computed tomography (PET/CT). METHODS: A retrospective analysis was conducted considering the texture features and conventional metabolic parameters in dual-time 18F-FDG PET/CT scans of PC patients. Features were extracted based on spatial distribution of 18F-FDG uptake in image. Firstly, the texture features and the conventional metabolic parameters of the delayed scan were both compared with that of the early scan. Statistically different data was defined among them. Secondly, the study evaluated the correlations between retention index (RI) of the texture features and the conventional metabolic parameters. Finally, the variation of texture features in dual-time PET/CT of resectable PC patients and unresectable PC patients was calculated separately. RESULTS: In total, 183 PC patients were analyzed retrospectively in this research. The conventional metabolic parameters were all statistically different between the early and delayed scans except for metabolic tumor volume (MTV). In the radiomics, there were 59 textural features. Nineteen of 59 texture features were statistically different between the early and delayed scans. Features that were more than 10% different during two scans were observed in a substantial percentage of patients. Weak correlations were only found between MTV, TLG (Total lesion glycolysis), SUVpeak and the RI of some texture features in early or delayed scans. There were obviously fewer features with significant difference in resectable PC group than in unresectable PC group. Most features showing the difference in unresectable group while no significant difference in resectable group. CONCLUSIONS: This study investigated the change and inner correlations of quantitative tumoral metabolic heterogeneity in the dual-time 18F-FDG-PET/CT scan of PC patients. Some features displayed the difference between dual-time scans. Conventional metabolic parameters were weakly related to the change of texture feature. The change of texture feature in resectable PC group was different from that in unresectable PC group. This result is potential to provide more information for the image evaluation of PC.

Retraction: ASIC1a involves acidic microenvironment-induced activation and autophagy of pancreatic stellate cells.

[This retracts the article DOI: 10.1039/C8RA03679A.].

Diagnostic Performance of Theranostic Radionuclides Used in Transarterial Radioembolization for Liver Cancer.

Primary liver tumor with hepatocellular carcinoma accounting for 75-80% of all such tumors, is one of the global leading causes of cancer-related death, especially in cirrhotic patients. Liver tumors are highly hypervascularized via the hepatic artery, while normal liver tissues are mainly supplied by the portal vein; consequently, intra-arterially delivered treatment, which includes transarterial chemoembolization (TACE) and transarterial radioembolization (TARE), is deemed as a palliative treatment. With the development of nuclear technology and radiochemistry, TARE has become an alternative for patients with hepatic cancer, especially for patients who failed other therapies, or for patients who need tumor downstaging treatment. In practice, some radionuclides have suitable physicochemical characteristics to act as radioactive embolism agents. Among them, 90Y emits ß rays only and is suitable for bremsstrahlung single photon emission computed tomography (BS SPECT) and positron emission tomography (PET); meanwhile, some others, such as 131I, 153Sm, 166Ho, 177Lu, 186Re, and 188Re, emit both ß and γ rays, enabling embolism beads to play a role in both therapy and single photon emission computed tomography (SPECT) imaging. During TARE, concomitant imaging provide additive diagnostic information and help to guide the course of liver cancer treatment. Therefore, we review the theranostic radionuclides that have been used or could potentially be used in TARE for liver cancer and focus on the clinical benefits of diagnostic applications, including real-time monitoring of embolism beads, evaluating irradiation dose, predicting therapy effects, and corresponding adjustments to TARE.

Sub-Micrometer Au@PDA-125 I Particles as Theranostic Embolism Beads for Radiosensitization and SPECT/CT Monitoring.

Au nanoparticles (3.8 ± 0.6 nm) are assembled to sub-micrometer Au particles (186.3 ± 20.4 nm) and covered with adhesive polydopamine (PDA) as embolism beads (198.8 ± 23.2 nm). Radioactive iodine-125 is labeled to Au@PDA to introduce the function of intra-irradiation. For the therapeutic effects of Au@PDA-125 I, Au particles sensitize the radiation to MHCC97H hepatoma cells and tumor-bearing mice. At the cellular level, after being treated with a relatively low-dose (5 Gy) γ-ray, Au-sensitized radiotherapy (RT) leads to an immediate increase of intracellular reactive oxygen species, accompanying with an increase of cell apoptosis. Due to the intra-irradiation, self-healing of RT-leaded DNA double-strand breakage is suppressed, inducing a further increase of cell apoptosis after RT treatment. Likewise, 3 cycles of sensitized RT leads to a valid control of tumor volume growth, but Au@PDA-125 I has no harm or radioactive residual on or in the radiosensitive organs, including the thyroid, heart, lungs, liver, and spleen. Additionally, photons emitted from 125 I and high X-ray absorption of the Au element makes the beads suitable for single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Therefore, as theranostic embolism beads, Au@PDA-125 I can both enhance the therapeutic effects of external RT, and provide a real-time SPECT/CT monitoring of therapeutic time window.

Retracted Article: ASIC1a involves acidic microenvironment-induced activation and autophagy of pancreatic stellate cells.

Acid-sensing ion channel 1a (ASIC1a), as a member of the proton-gated cation channel family, can be activated by low extracellular pH, and takes part in many acidity-associated physiopathological processes. However, whether ASIC1a is expressed in human pancreatic stellate cells (PSCs) and involved in acid-induced physiopathological events has not been reported yet. In this study, we investigated the expression of ASIC1a in PSCs and its possible role in the activation and autophagy of PSCs evoked by extracellular acid. Our results show that ASIC1a is present in PSCs, and an enhanced expression of ASIC1a occurs under acid stimuli. More importantly, the activation and autophagy of PSCs can be induced in acidic medium, and inhibition of ASIC1a by ASIC1a-specific blocker psalmotoxin-1 (PcTx1) or siRNA knockdown could suppress these two acid-associated processes. Collectively, our present study reports for the first time that ASIC1a is expressed in PSCs, and provides evidence for the involvement of ASIC1a in the acidic microenvironment-induced activation and autophagy of PSCs.

18F- FDG PET/CT helps differentiate autoimmune pancreatitis from pancreatic cancer.

BACKGROUND: 18F-FDG PET/CT could satisfactorily show pancreatic and extra-pancreatic lesions in AIP, which can be mistaken for pancreatic cancer (PC). This study aimed to identify 18F-FDG PET/CT findings that might differentiate AIP from PC. METHODS: FDG-PET/CT findings of 26 AIP and 40 PC patients were reviewed. Pancreatic and extra-pancreatic lesions related findings, including maximum standardized uptake values (SUVmax) and patterns of FDG uptake, were identified and compared. RESULTS: All 26 patients with AIP had increased pancreatic FDG uptake. Focal abnormal pancreatic FDG activities were found in 38/40 (95.00%) PC patients, while longitudinal were found in 18/26 (69.23%) AIP patients. SUVmax was significantly different between AIP and PC, both in early and delayed PET/CT scans (p < 0.05). AUCs were 0.700 (early SUVmax), 0.687 (delayed SUVmax), 0.683 (early lesions/liver SUVmax), and 0.715 (delayed lesion/liver SUVmax). Bile duct related abnormalities were found in 12/26 (46.15%) AIP and 10/40 (25.00%) PC patients, respectively. Incidentally, salivary and prostate gland SUVmax in AIP patients were higher compared with those of PC patients (p < 0.05). In males,an inverted "V" shaped high FDG uptake in the prostate was more frequent in AIP than PC patients (56.00%, 14/25 vs. 5.71%, 2/35). Increased FDG activity in extra-pancreatic bile duct was present in 4/26 of AIP patients, while was observed in none of the PC patients. Only in AIP patients, both diffuse pancreatic FDG accumulation and increased inverted "V" shaped FDG uptake in the prostate could be found simultaneously. CONCLUSIONS: 18F-FDG PET/CT findings might help differentiate AIP from PC.

Mannose-coated gadolinium liposomes for improved magnetic resonance imaging in acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is an acute inflammatory condition of the pancreas. The symptoms, treatment, and prognosis of mild and severe AP are different, and severe AP is a potentially life-threatening disease with a high incidence of complications and high mortality rate. Thus, it is urgent to develop an effective approach to reliably discriminate between mild and severe AP. METHODS: We have developed novel gadolinium-diethylenetriaminepentaacetic (Gd-DTPA)-loaded mannosylated liposomes (named thereafter M-Gd-NL) that preferably target macrophages in AP. The targeting ability of M-Gd-NL toward macrophages in AP and its ability to discriminate between mild and severe AP were evaluated. RESULTS: The liposomes were of desired particle size (~100 nm), Gd-DTPA encapsulation efficiency (~85%), and stability. M-Gd-NL and non-targeted Gd-DTPA-loaded liposomes (Gd-NL) exhibited increased relaxivity compared with Gd-DTPA. Compared with Gd-NL and Gd-DTPA, M-Gd-NL showed increased uptake in macrophages, resulting in increased T1 imaging ability both in vitro (macrophage cell line) and in vivo (severe AP model). Importantly, M-Gd-NL had the ability to discriminate between mild and severe AP, as reflected by a significantly higher T1 magnetic resonance imaging signal in severe AP than in mild AP. M-Gd-NL did not show severe organ toxicity in rats. CONCLUSION: Our data suggest that M-Gd-NL had enhanced magnetic resonance imaging ability by targeting macrophages in AP and good ability to discriminate between mild and severe AP. We believe that M-Gd-NL could shed new light on the diagnosis of AP in the near future.

[Protein and mRNA expression of CTGF, CYR61, VEGF-C and VEGFR-2 in bone marrow of leukemia patients and its correlation with clinical features].

This study was aimed to investigate the mRNA and protein expression of CTGF, CYR61, VEGF-C and VEGFR-2 in bone marrow of patients with leukemia, and to analyze the role and clinical significance of these 4 factors in genesis and development of leukemia, infiltration and metastasis of leukemic cells. A total of 100 cases of newly diagnosed leukemia, 26 cases of acute leukemia in complete remission and 30 controls were enrolled in this study. The mononuclear cells of bone marrow were collected, the mRNA and protein expression levels of CTGF, CYR61, VEGF-C, VEGFR-2 in leukemia patients and controls were detected by real time PCR and Western blot, respectively. The results showed that the mRNA and protein expression levels of above mentioned 4 factors were significantly higher than those in control (P < 0.05), only CTGF mRNA expression in AL patients after complete remission showed statistical difference as compared with control (P < 0.05), but the expression of CTGF mRNA showed statistical significance in different bone marrow hyperplasia of acute leukemia (P < 0.05). The expression level of CTGF protein showed difference in different chromosome karyotypes of leukemia (P < 0.05). The expression levels of CYR61 and VEGF-C proteins showed statistical difference in different bone marrow hyperplasia of acute leukemia (P < 0.05). The expression level of CTGF, CYR61, VEGF-C mRNA and protein in CML group were higher than that in control group. The expression levels of CTGF and CYR61 protein were higher than that in control. The mRNA and protein expression levels of above-mentioned 4 factors in sex and infiltration lf leukemic cells did not show statistical significance(P < 0.05). In correlative analysis, the mRNA expressions of above mentioned 4 factors were positively correlated with bone marrow blast count(P < 0.05), the protein expression of CTGF, CYR61 and VEGF-C were positively correlated with bone marrow blast count. It is concluded that the CTGF, CYR61, VEGF-C and VEGFR-2 mRNA and protein play a role in acute leukemia. In acute leukemia (AML/ALL), the expression of above mentioned factor was high, but except VEGFR-2. Most of them were positively correlated with bone marrow blast count. Joint block of these angiogenesis-related factors is likely to play an important role in targeting treatment of leukemia.

[Expression of CYR61, CTGF, VEGF-C, VEGFR-2 mRNA in bone marrow of leukemia patients and its clinical significance].

The study was aimed to detect the levels of CYR61, CTGF, VEGF-C, VEGFR-2 mRNA in bone marrow (BM) of leukemia patients and investigate the interaction of CYR61, CTGF, VEGF-C, VEGFR-2 proteins in occurrence, development, infiltration and metastasis of leukemia and its clinical significance, to find a new tumor marker for diagnosis and treatment of leukemia with some new directions. 74 patients with leukemia were enrolled in this study, 38 out of them were males and 36 were females, aged from 6 to 77 years old with the median age of 45 years old. In the control group, 7 males and 5 females, aged from 16 to 78 years old with the median age of 46. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to detect the levels of CYR61, CTGF, VEGF-C, VEGFR-2 mRNA. The results showed that the levels of CYR61, CTGF, VEGF-C, VEGFR-2 mRNA in BM of newly diagnosed patients with acute and chronic leukemia of each group were significantly higher as compared with the control group (p < 0.05). The levels of CYR61, CTGF mRNA in acute leukemia remission group were significantly higher than those in control group (p = 0.039, 0.025). The level of CTGF mRNA was highest in B-ALL group, and was higher than that in AML, CML, CLL, T-ALL groups (p = 0.002, 0.034, 0.002, 0.010). In AML group, mRNA expressions of CYR61 and CTGF, CYR61 and VEGF-C, CTGF and VEGFR-2 were positively correlated (r = 0.452, 0.466, 0.464; p = 0.045, 0.038, 0.039), and in CML group mRNA expression of CYR61 and VEGF-C was positively correlated (r = 0.882, p = 0.000). The expression levels of VEGF-C, VEGFR-2 mRNA in acute leukemia patients with extramedullary infiltration were higher than those in acute leukemia patients without extramedullary infiltration (p = 0.028, 0.047). VEGF-C mRNA expression and the original cell counts in AML group were positively correlated (r = 0.418, p = 0.034). It is concluded that CYR61, CTGF, VEGF-C and VEGFR-2 interact each other in the pathogenesis of leukemia, promote the development, metastasis and infiltration of leukemia; and these factors in different types of leukemia and extramedullary infiltration are different, which may become tumor markers of leukemia; and blocking VEGF-C and VEGFR-2 may block tumor growth and metastasis.