Search

To compare the effects of aminosalicylic acid, glucocorticoids and immunosuppressants on the expression levels of multidrug resistance genes in patients with ulcerative colitis (UC), with the aim of providing a theoretical and therapeutic basis for the diagnosis, treatment, and prevention of UC. Fresh colonic mucosal tissues or postoperative pathological biopsies from 148 UC patients were collected, and the distribution sites and morphology of P-glycoprotein (P-gp) were detected using immunohistochemical staining. RT-PCR was used to quantify the expression levels of multidrug resistance gene (MDR1) mRNA before and after the corresponding treatment, and the effects of aminosalicylic acid, glucocorticoids and immunosuppressive drugs on P-gp were compared. In addition, the effects of the three drugs on MDR1 mRNA were analyzed. Administration of 5-aminosalicylic acid (5-ASA) drugs did not correlate with MDR1 expression in UC, whereas administration of glucocorticoids and immunosuppressive drugs was positively correlated with MDR1 expression profile. The expression levels of MDR1 mRNA and its product P-gp were significantly upregulated in patients who did not respond to glucocorticoids and immunosuppressive drugs. 5-ASA had no effect on the expression levels of MDR1 and its product P-gp in patients with a confirmed diagnosis of UC. However, the use of glucocorticoids and immunosuppressants can increase the expression level of MDR1. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the effect of technetium-99m (99mTc)-labeled prostate-specific membrane antigen (PSMA)-based image-guided surgery on the oncologic outcomes for patients with primary or recurrent prostate cancer (PCa).Methods: This study retrospectively analyzed 54 consecutive patients with PCa who underwent 99mTc-labeled PSMA-based image-guided surgery between January 2016 and September 2017. These patients received a radical prostatectomy (RP) with pelvic lymph node dissection (PLND) or salvage lymph node dissection (sLND). The resected specimens were compared with findings of postoperative histologic analysis. The responses to the treatment were recorded during the follow-up period.Results: In 31 patients, PSMA single-photon emission computerized tomography (SPECT) and computed tomography (CT) could find 52 suspicious lymph node metastases (LNMs). With the help of PSMA SPECT/CT, 12 patients with recurrence received sLND, 19 primary PCa patients received RP with extended PLND, and 23 primary PCa patients received RP with standard PLND. The findings showed that PSMA SPECT/CT could detect LNMs with high sensitivity and specificity. In six patients, PSMA SPECT/CT could find more LNMs that were not found by MRI and help to modify the extent of lymphadenectomy. At the latest follow-up evaluation, 39 patients showed a biochemical response (BR), 9 patients showed a biochemical recurrence (BCR) after BR, and 6 patients never exhibited BR. The patients who received RP with standard PLND or extended PLND had a better prostate-specific antigen (PSA) response than the patients who received sLND. The patients with pelvic LNMs also had a better PSA response than the patients with retroperitoneal LNMs.Conclusions: This study showed that 99mTc-PSMA SPECT/CT-guided surgery can remove more LNMs than conventional imaging with high sensitivity and specificity and delay disease progression in PCa patients. [ABSTRACT FROM AUTHOR]

Purpose: Tumour burden is one of the most important prognosticators for pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate the predictive significance of metabolic tumour burden measured by F-FDG PET/CT in patients with resectable PDAC. Methods: Included in the study were 122 PDAC patients who received preoperative F-FDG PET/CT examination and radical pancreatectomy. Metabolic tumour burden in terms of metabolic tumour volume (MTV) and total lesion glycolysis (TLG), pathological tumour burden (tumour size), serum tumour burden (baseline serum CA19-9 level), and metabolic activity (maximum standard uptake value, SUVmax) were determined, and compared for their performance in predicting overall survival (OS) and recurrence-free survival (RFS). Results: MTV and TLG were significantly associated with baseline serum CA19-9 level ( P = 0.001 for MTV, P < 0.001 for TLG) and tumour size ( P < 0.001 for MTV, P = 0.001 for TLG). Multivariate analysis showed that MTV, TLG and baseline serum CA19-9 level as either categorical or continuous variables, but not tumour size or SUVmax, were independent risk predictors for both OS and RFS. Time-dependent receiving operating characteristics analysis further indicated that better predictive performances for OS and RFS were achieved by MTV and TLG compared to baseline serum CA19-9 level, SUVmax and tumour size ( P < 0.001 for all). Conclusion: MTV and TLG showed strong consistency with baseline serum CA19-9 level in better predicting OS and RFS, and might serve as surrogate markers for prediction of outcome in patients with resectable PDAC. [ABSTRACT FROM AUTHOR]

There is an increasing need to develop non-invasive molecular imaging strategies for visualizing and quantifying apoptosis status of diseases (especially for cancer) for diagnosis and monitoring treatment response. Since externalization of phosphatidylserine (PS) is one of the early molecular events during apoptosis, Annexin B1 (AnxB1), a member of Annexins family with high affinity toward the head group of PS, could be a potential positron emission tomography (PET) imaging probe for imaging cell death process after labeled by positron-emitting nuclides, such as F. In the present study, we investigated a novel PET probe, F-labeled Annexin B1 (F-AnxB1), for apoptosis imaging. F-AnxB1 was prepared reliably by conjugating AnxB1 with a F-tag, N-succinimidyl 4-[F]fluorobenzoate ([F]SFB), in a radiolabeling yield of about 20 % within 40 min. The in vitro binding of F-AnxB1 with apoptotic cells induced by anti-Fas antibody showed twofold increase compared to those without treatment, confirmed by flow cytometric analysis with AnxV-FITC/PI staining. Stability tests demonstrated F-AnxB1 was rather stable in vitro and in vivo without degradation. The serial F-AnxB1 PET/CT scans in healthy rats outlined its biodistribution and pharmacokinetics, indicating a rapid renal clearance and predominant accumulation into kidney and bladder at 2 h p.i. F-AnxB1 PET/CT imaging was successfully applied to visualize in vivo apoptosis sites in tumor induced by chemotherapy and in kidney simulated by ischemia-reperfusion injury. The high-contrast images were obtained at 2 h p.i. to delineate apoptotic tumor. Apoptotic region could be still identified by F-AnxB1 PET 4 h p.i., despite the high probe retention in kidneys. In summary, we have developed F-AnxB1 as a PS-specific PET probe for the apoptosis detection and quantification which could have broad applications from disease diagnosis to treatment monitoring, especially in the cases of cancer. [ABSTRACT FROM AUTHOR]

Two cases of postoperative female patients with ovarian serous papillary carcinoma were referred for F-18 Fluorodeoxyglucose (F-18 FDG) PET/CT to evaluate suspicious recurrence and/or metastasis. One patient presented with multiple extensive calcified lesions with increased FDG uptake in the abdominopelvic cavity and the series of PET/CT scans showed progression of disease after chemotherapy. The other patient presented with three calcified masses with intensive uptake of FDG located in the left pelvis, the right subphrenic region, and the right supradiaphragmatic area, respectively. These suggest that F-18 FDG PET/CT can be useful in identifying malignant calcification and assessing therapeutic response of calcified malignancy. [ABSTRACT FROM AUTHOR]

The need of reliable production of N-succinimidyl 4-[F]fluorobenzoate ([F]SFB), a versatile F-labeled prosthetic group for protein labeling, has increased dramatically due to the easy availability of proteins or their engineered derivatives for targeted molecular imaging. A module-assisted radiosynthesis of [F]SFB was developed using a three-step, one-pot procedure and ethyl 4-(trimethylammonium)benzoate triflate ( 1) as the starting material. The radiochemical transformations were carried out in a general-purpose, custom-made module and streamlined by an anhydrous deprotection strategy using t-BuOK/DMSO. After HPLC-purification, [F]SFB was synthesized in radiochemical yields of 20-30% ( n > 10, not decay-corrected) and excellent radiochemical and chemical purities (>98%). The total synthesis and purification time required is ~90 min. Using the purified [F]SFB, three F-labeled proteins, bovine serum albumin (BSA), chicken egg albumin (CEA) and transferrin, were synthesized in yields of 61.0-79.5%. The F-Annexin V for apoptosis imaging was also produced in 5% radiolabeling yield and >95% radiochemical purity. [ABSTRACT FROM AUTHOR]