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Shaojia Wang, Jiajia Li, Jie Xie, Fei Liu, Yachen Duan, Yong Wu, Shenglin Huang, Xianghuo He, Ziliang Wang, Xiaohua Wu
Although PD-L1 has been shown to play a well-characterized role in inhibiting antitumor immunity via engagement of its receptor PD-1 in T lymphocytes, little is known about the tumor cell-intrinsic function of PD-L1 and its association with prognosis. Here, we investigate this issue and dissect the molecular mechanisms underlying the role of PD-L1 in glucose metabolism, proliferation, migration, and invasion in human cervical cancer cells. As a result, we found that PD-L1 overexpression in cervical cancer cells increases glucose metabolism and metastasis-related behaviors...
April 30, 2018: Oncogene
Xiaohui Wang, Jun Zhang, Hubing Wu, Yumin Li, Peter S Conti, Kai Chen
Heat shock protein 90 (Hsp90) plays a vital role in the progress of malignant disease and elevated Hsp90 expression has been reported in pancreatic cancer. In this study, we radiolabeled a dimeric Sansalvamide A derivative (Di-San A1) with 64 Cu, and evaluated the feasibility of using 64 Cu-Di-San A1 for PET imaging of Hsp90 expression in a mouse model of pancreatic cancer. A macrocyclic chelator NOTA (1,4,7-triazacyclononane-1,4,7-trisacetic acid) was conjugated to Di-San A1. 64 Cu-Di-San A1 was successfully prepared in a radiochemical yield > 97% with a radiochemical purity > 98%...
April 24, 2018: Amino Acids
Li-Juan Wang, Hong-Sheng Li, Quan-Shi Wang, Hu-Bing Wu, Yan-Jiang Han, Wen-Lan Zhou, Meng Wang, Shun Huang
A novel tumor stroma targeting and membrane-penetrating cyclic peptide, named iCREKA, was designed and labeled by fluorescein isothiocyanate (FITC) and positron emitter 18 F to build the tumor-targeting tracers. The FITC-iCREKA was proved to have significantly higher cellular uptake in the glioma U87 cells in the presence of activated MMP-2 than that in absence of activated MMP-2 by cells fluorescence test in vitro . The tumor tissue fluorescence microscope imaging demonstrated that FITC-iCREKA accumulated in the walls of the blood vessels and the surrounding stroma in the glioma tumor at 1 h after intravenous injection...
2018: Contrast Media & Molecular Imaging
Nicole Maninger, Sally P Mendoza, Donald R Williams, William A Mason, Simon R Cherry, Douglas J Rowland, Thomas Schaefer, Karen L Bales
Understanding the neurobiology of social bonding in non-human primates is a critical step in understanding the evolution of monogamy, as well as understanding the neural substrates for emotion and behavior. Coppery titi monkeys ( Callicebus cupreus ) form strong pair bonds, characterized by selective preference for their pair mate, mate-guarding, physiological and behavioral agitation upon separation, and social buffering. Mate-guarding, or the "maintenance" phase of pair bonding, is relatively under-studied in primates...
October 2017: Frontiers in Ecology and Evolution
Rufael Chekol, Viswas Raja Solomon, Elahe Alizadeh, Wendy Bernhard, Darrell Fisher, Wayne Hill, Kris Barreto, John Francis DeCoteau, Angel Casaco Parada, Clarence Ronald Geyer, Humphrey Fonge
Rationale: Epidermal growth factor receptor (EGFR) upregulation is associated with enhanced proliferation and drug resistance in a number of cancers. Nimotuzumab is a humanized monoclonal antibody with high affinity for EGFR. The objective of this study was to determine if 89 Zr-DFO-nimotuzumab could be suitable for human use as a PET probe for quantifying EGFR in vivo . Methods: To evaluate the pharmacokinetics, biodistribution, microPET imaging, radiation dosimetry, and normal tissue toxicity in tumor and non-tumor bearing mice of 89 Zr-desferoxamine-nimotuzumab (89 Zr-DFO-nimotuzumab) of a product prepared under GMP conditions...
March 30, 2018: Oncotarget
Stephanie Robu, Alexander Schmidt, Matthias Eiber, Margret Schottelius, Thomas Günther, Behrooz Hooshyar Yousefi, Markus Schwaiger, Hans-Jürgen Wester
BACKGROUND: Due to its high and consistent expression in prostate cancer (PCa), the prostate-specific membrane antigen (PSMA) represents an ideal target for molecular imaging and targeted therapy using highly specific radiolabeled PSMA ligands. To address the continuously growing clinical demand for 18 F-labeled PSMA-probes, we developed two novel Glu-urea-Glu-(EuE)-based inhibitors, EuE-k-18 F-FBOA (1) and EuE-k-β-a-18 F-FPyl (2), both with optimized linker structure and different 18 F-labeled aromatic moieties...
April 12, 2018: EJNMMI Research
Daphne Lobeek, Gerben M Franssen, Michelle T Ma, Hans-Jürgen Wester, Clemens Decristoforo, Wim J G Oyen, Otto C Boerman, Samantha Y A Terry, Mark Rijpkema
Rationale: αv β3 integrins play an important role in angiogenesis and cell migration of cancers. They are highly expressed on activated endothelial cells of newly formed blood vessels. Here, we compare the targeting characteristics of four68 Ga-labeled multimeric cyclic arginine-glycine-aspartate RGD-based tracers in an αv β3 integrin-expressing tumor model and in a tumor model where αv β3 integrin is expressed solely on the neovasculature. Methods: Female BALB/c nude mice were subcutaneously injected with SK-RC-52 (αv β3 integrin-positive) or FaDu (αv β3 integrin-negative) tumor cells...
April 6, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Xiangyuan Chen, Qichao Wu, Pengfei Sun, Yanjun Zhao, Minmin Zhu, Changhong Miao
BACKGROUND/AIMS: To investigate the effect of propofol on glucose metabolism in colorectal cancer cells and in an in vivo xenograft model. METHODS: Glucose metabolism was assessed by measuring the extracellular acidification rate in HT29 and SW480 colorectal cancer cells. Quantitative real-time PCR and western blot analyses were used to detect mRNA and protein levels, respectively. Intracellular calcium was assessed by using a Fluo-3 AM fluorescence kit. Micro-positron emission tomography/computed tomography (microPET/CT) imaging was used to analyze glucose metabolism in the tumors of the xenograft model...
March 26, 2018: Cellular Physiology and Biochemistry
Kirstin A Zettlitz, Wen-Ting K Tsai, Scott M Knowles, Naoko Kobayashi, Timothy R Donahue, Robert E Reiter, Anna M Wu
Pancreatic cancer has a high mortality rate due to late diagnosis and the tendency to invade surrounding tissues and metastasize at an early stage. A molecular imaging agent that enables both pre-surgery antigen-specific positron emission tomography (immunoPET) and intra-operative near-infrared fluorescent (NIRF)-guidance could benefit diagnosis, staging and surgical resection of pancreatic cancer, which remains the only curative treatment. Methods: A dually labeled probe was developed based on A2 cys-diabody (A2cDb) targeting the cell surface antigen prostate stem cell antigen (PSCA) that is expressed in a majority of pancreatic cancers...
March 30, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Katharina Lückerath, Andreea D Stuparu, Liu Wei, Woosuk Kim, Caius G Radu, Christine E Mona, Jeremie Calais, Matthew Rettig, Robert E Reiter, Johannes Czernin, Roger Slavik, Ken Herrmann, Matthias Eiber, Wolfgang Fendler
Aim: To improve prostate specific membrane antigen (PSMA) targeted theranostic approaches, robust murine models of prostate cancer are needed. However, important characteristics of preclinical PSMA imaging, i.e. reproducibility of the imaging signal and the relationship between quantitative cell surface PSMA expression and lesion detectability with microPET/CT, have not been defined yet. Methods: Murine prostate cancer RM1 sublines expressing varying levels of human PSMA were injected into the shoulder of C57Bl/6 mice on day 0...
March 30, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Gabriele Zanirati, Pamella Nunes Azevedo, Gianina Teribele Venturin, Samuel Greggio, Allan Marinho Alcará, Eduardo R Zimmer, Paula Kopschina Feltes, Jaderson Costa DaCosta
OBJECTIVE: Temporal lobe epilepsy (TLE) is one of the most common types of epilepsy syndromes in the world. Depression is an important comorbidity of epilepsy, which has been reported in patients with TLE and in different experimental models of epilepsy. However, there is no established consensus on which brain regions are associated with the manifestation of depression in epilepsy. Here, we investigated the alterations in cerebral glucose metabolism and the metabolic network in the pilocarpine-induced rat model of epilepsy and correlated it with depressive behavior during the chronic phase of epilepsy...
March 30, 2018: Epilepsia
Ermelinda Lucente, Hongguang Liu, Yang Liu, Xiang Hu, Enza Lacivita, Marcello Leopoldo, Zhen Cheng
Bombesin receptor 2 (BB2 ) and integrin αv β3 receptor are privileged targets for molecular imaging of cancer because their overexpression in a number of tumor tissues. The most recent developments in heterodimer-based radiopharmaceuticals concern BB2 - and integrin αv β3 -targeting compounds, consisting of bombesin (BBN) and RGD peptides, connected through short length linkers. Molecular imaging probes based on RGD-BBN heterodimer design exhibit improved tumor targeting efficacy compared to the single-receptor targeting peptide monomers...
March 27, 2018: Bioconjugate Chemistry
Wenhui Ma, Fanfan Fu, Jingyi Zhu, Rui Huang, Yizhou Zhu, Zhenwei Liu, Jing Wang, Peter S Conti, Xiangyang Shi, Kai Chen
We report the use of multifunctional folic acid (FA)-modified dendrimers as a platform to radiolabel with 64Cu for PET imaging of folate receptor (FR)-expressing tumors. In this study, amine-terminated generation 5 (G5) poly(amidoamine) dendrimers were sequentially modified with fluorescein isothiocyanate (FI), FA, and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), followed by acetylation of the remaining dendrimer terminal amines. The as-formed multifunctional DOTA-FA-FI-G5·NHAc dendrimers were then radiolabeled with 64Cu via the DOTA chelation...
March 16, 2018: Nanoscale
Fanxing Zeng, Jonathon A Nye, Ronald J Voll, Leonard Howell, Mark M Goodman
Nine pyridyloxypyridyl indole carboxamides were synthesized and displayed high affinities for 5-HT2C receptors and high selectivity over 5-HT2A and 5-HT2B . Among them, 6-methyl- N -[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]1 H -indole-3-carboxamide ( 8 ) exhibits the highest 5-HT2C binding affinity ( K i = 1.3 nM) and high selectivity over 5-HT2A (∼1000 times) and 5-HT2B (∼140 times). [11 C] 8 was synthesized by palladium-catalyzed coupling reaction between pinacolboranate 16 and [11 C]CH3 I with an average radiochemical yield of 27 ± 4% ( n = 8, decay-corrected from end of [11 C]CH3 I synthesis)...
March 8, 2018: ACS Medicinal Chemistry Letters
Zhengyuan Zhou, Satish K Chitneni, Nick Devoogdt, Michael R Zalutsky, Ganesan Vaidyanathan
In a previous study, we evaluated a HER2-specific single domain antibody fragment (sdAb) 2Rs15d labeled with18 F via conjugation of a residualizing prosthetic agent that was synthesized by copper-catalyzed azide-alkyne cycloaddition (CuAAC). In order to potentially increase overall efficiency and decrease the time required for labeling, we now investigate the use of a strain-promoted azide-alkyne cycloaddition (SPAAC) between the 2Rs15d sdAb, which had been pre-derivatized with an azide-containing residualizing moiety, and an18 F-labeled aza-dibenzocyclooctyne derivative...
March 10, 2018: Bioorganic & Medicinal Chemistry
Zhihao Zha, Karl Ploessl, Brian P Lieberman, Limin Wang, Hank F Kung
INTRODUCTION: Glutamine is an essential source of energy, metabolic substrates, and building block for supporting tumor proliferation. Previously, [18 F](2S,4R)4-fluoroglutamine (4F-Gln) was reported as a glutamine-related metabolic imaging agent. To improve the in vivo kinetics of this radiotracer, two new dipeptides, [18 F]Gly-(2S,4R)4-fluoroglutamine (Gly-4F-Gln) and [18 F]Ala-(2S,4R)4-fluoroglutamine (Ala-4F-Gln) were investigated. METHODS: Radiolabeling was performed via 2-steps18 F-fluorination...
February 13, 2018: Nuclear Medicine and Biology
Mehran Makvandi, Austin Pantel, Lauren Schwartz, Erin Schubert, Kuiying Xu, Chia-Ju Hsieh, Catherine Hou, Hyoung Kim, Chi-Chang Weng, Harrison Winters, Robert Doot, Michael D Farwell, Daniel A Pryma, Roger A Greenberg, David A Mankoff, Fiona Simpkins, Robert H Mach, Lilie L Lin
BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitors are effective in a broad population of patients with ovarian cancer; however, resistance caused by low enzyme expression of the drug target PARP-1 remains to be clinically evaluated in this context. We hypothesize that PARP-1 expression is variable in ovarian cancer and can be quantified in primary and metastatic disease using a novel PET imaging agent. METHODS: We used a translational approach to describe the significance of PET imaging of PARP-1 in ovarian cancer...
May 1, 2018: Journal of Clinical Investigation
Shuai Liu, Bingxin Gu, Jianping Zhang, Yongping Zhang, Xiaoping Xu, Huiyu Yuan, Yingjian Zhang, Zhongyi Yang
OBJECTIVE: Our study aimed to investigate the feasibility of PET/CT for monitoring the influence of fulvestrant on sensitizing docetaxel by downregulating ERα in ERα+ breast cancer. METHODS: Docetaxel-insensitive ERα+ breast cancer cells (DIS-ZR751) were established, identified and cultured. ERα expression, toxicity and viability of DIS-ZR751 were analyzed before and after treatment in vitro. DIS-ZR751-bearing nude mice were randomly divided into four groups according to different treatments: blank (DIS-ZR751), docetaxel (DIS-ZR751+DOC), fulvestrant (DIS-ZR751+FUL), and combination treatment (DIS-ZR751+DOC+FUL)...
May 2018: Annals of Nuclear Medicine
Duo Xu, Rongqiang Zhuang, Linyi You, Zhide Guo, Xiangyu Wang, Chenyu Peng, Deliang Zhang, Pu Zhang, Hua Wu, Weimin Pan, Xianzhong Zhang
INTRODUCTION: A novel radiotracer 1‑(2‑(2‑(2‑[18 F]fluoroethoxy)ethoxy)ethyl)‑1H‑1,2,3‑triazole‑estradiol ([18 F]FETE) was successfully synthesized, characterized and evaluated in mice for estrogen receptor (ER)-positive breast cancer targeting with positron emission tomography (PET) imaging. METHODS: The tosylate precursor 3 was radiolabeled with 18 F and then reacted with 17α‑ethinyl‑estradiol to produce the final [18 F]FETE. The physicochemical properties of [18 F]FETE were tested in vitro, including determination of the octanol/water partition coefficient, stability and cellular uptake in MCF-7 (ER-positive) and MDA-MB-231 (ER-negative) cells...
April 2018: Nuclear Medicine and Biology
Zhihao Zha, Karl Ploessl, Seok Rye Choi, Zehui Wu, Lin Zhu, Hank F Kung
INTRODUCTION: Prostate specific membrane antigen (PSMA) is a well-established target for diagnostic and therapeutic applications for prostate cancer. It is know that [68 Ga]PSMA 11 ([68 Ga]Glu-NH-CO-NH-Lys(Ahx)-HBED-CC) is the most well studied PET imaging agent for detecting over expressed PSMA binding sites of tumors in humans. In an effort to provide new agents with improved characteristics for PET imaging, we report a novel [68 Ga]-Glu-NH-CO-NH-Lys(Ahx)-linker-HBED-CC conjugate with a novel O-(carboxymethyl)-L-tyrosine, as the linker group...
April 2018: Nuclear Medicine and Biology
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