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Nuclear Medicine and Biology

Michael R Kilbourn, Peter J H Scott
No abstract text is available yet for this article.
September 3, 2018: Nuclear Medicine and Biology
Nisha Singh, Mattia Veronese, Jim O'Doherty, Teresa Sementa, Salvatore Bongarzone, Diana Cash, Camilla Simmons, Marco Arcolin, Paul K Marsden, Antony Gee, Federico E Turkheimer
INTRODUCTION: The development of clinically useful tracers for PET imaging is enormously challenging and expensive. The intranasal (IN) route of administration is purported to be a viable route for delivering drugs to the brain but has, as yet, not been investigated for the delivery of PET tracers. If the intranasal (IN) pathway presents a viable option, it extends the PET imaging field by increasing the number of tracers available for human use. Here we report the results of a rodent study testing the feasibility of the IN route to administer radiotracers for brain PET imaging...
August 30, 2018: Nuclear Medicine and Biology
Dong Zhou, Jinbin Xu, Cedric Mpoy, Wenhua Chu, Sung Hoon Kim, Huifangjie Li, Buck E Rogers, John A Katzenellenbogen
INTRODUCTION: Poly (ADP-ribose) polymerase-1 (PARP-1) plays many roles in prostate cancer (PC), such as mediating DNA damage repair, transcriptional regulation and nuclear hormone receptor signaling. Because of this, PARP-1 has been targeted for therapy in PC, and non-invasive imaging of PARP-1 could help predict which patients are likely to respond to such therapy. Several PARP-1 positron emission tomography (PET) imaging agents have been developed and show promise for imaging PARP-1 expression in breast, brain, and lung cancer in small animals, but not as yet in prostate cancer...
August 24, 2018: Nuclear Medicine and Biology
Yi Li, Cheng Liu, Xiaoping Xu, Xiaoling Lu, Jianming Luo, Brian Gray, Koon Y Pak, Jingyi Cheng, Yingjian Zhang
OBJECTIVE: Apoptosis plays a crucial role in many biological processes, especially in cancer. However, real-time monitoring of apoptosis is challenging. [99m Tc]duramycin can selectively target an apoptosis biomarker: phosphatidylethanolamine (PE), which is normally located on the intracellular cell-membrane surface but redistributes onto the outer cell-membrane upon apoptosis. Therefore, 99m Tc-duramycin is a potential probe for non-invasive detection of apoptosis in real-time. The aim of this study was to evaluate the value of [99m Tc]duramycin for detecting early apoptotic response in tumors after chemotherapy, thus providing a tool for early prediction of curative effects in tumors...
August 9, 2018: Nuclear Medicine and Biology
Etienne Rousseau, Joseph Lau, Zhengxing Zhang, Carlos F Uribe, Hsiou-Ting Kuo, Chengcheng Zhang, Jutta Zeisler, Nadine Colpo, Kuo-Shyan Lin, François Bénard
INTRODUCTION: [177 Lu]Lu-DOTATATE peptide receptor radionuclide therapy is used for treatment of neuroendocrine tumours. We investigated whether prolonging blood residence time of [177 Lu]Lu-DOTATATE with albumin binders could increase tumour accumulation and tumour-to-kidney ratios for improved therapeutic efficacy. METHODS: DOTATATE and its derivatives with an albumin-binder motif (GluAB-DOTATATE and AspAB-DOTATATE) were prepared by solid-phase peptide synthesis...
August 9, 2018: Nuclear Medicine and Biology
Takashi Temma, Hidekazu Kawashima, Naoya Kondo, Makoto Yamazaki, Kazuhiro Koshino, Hidehiro Iida
INTRODUCTION: Lactate could serve as an energy source and signaling molecule in the brain, although there is insufficient in vivo evidence to support this possibility. Here we aimed to use a one-pot enzymatic synthetic procedure to synthesize l-[3-11 C]lactate that can be used to evaluate chemical forms in the blood after intravenous administration, and as a probe for pharmacokinetic analysis of lactate metabolism in in vivo positron emission tomography (PET) scans with normal and fasted rats...
July 7, 2018: Nuclear Medicine and Biology
Cong Li, Hui Liu, Dongban Duan, Zhenhan Zhou, Zhibo Liu
INTRODUCTION: The emerging evidence that demonstrated the extra-demand of glutamine for cancer surviving strongly called for the development of PET tracer for imaging glutamine uptake in cancer. In this work, [18 F]Gln-BF3 as a natural glutamine derivative was synthesized to explore its potential application of imaging glutamine uptake for cancer diagnosis. METHODS: [18 F]Gln-BF3 was prepared by deprotection of purified precursor trityl-Gln-BF3 (amide bond protected with triphenylmethyl group) using TFA and radiolabeled using 18 F-19 F isotope exchange protocol...
July 6, 2018: Nuclear Medicine and Biology
Renske M Raaphorst, Gert Luurtsema, Cindy J Schokker, Khaled A Attia, Robert C Schuit, Philip H Elsinga, Adriaan A Lammertsma, Albert D Windhorst
INTRODUCTION: Fluorine-18 labeled positron emission tomography (PET) tracers were developed to obtain more insight into the function of P-glycoprotein (P-gp) in relation to various conditions. They allow research in facilities without a cyclotron as they can be transported with a half-life of 110 min. As the metabolic stability of previously reported tracers [18 F]1 and [18 F]2 was poor, the purpose of this study was to improve this stability using deuterium substitution, creating verapamil analogs [18 F]1-d4 , [18 F]2-d4 , [18 F]3-d3 and [18 F]3-d7 ...
July 5, 2018: Nuclear Medicine and Biology
Yan Zhang, Futao Liu, Hao Xiao, Xinyue Yao, Genxun Li, Seok Rye Choi, Karl Ploessl, Zhihao Zha, Lin Zhu, Hank F Kung
OBJECTIVES: Serotonin transporters (SERT) play an important role in controlling serotonin concentration in the synaptic cleft and in managing postsynaptic signal transduction. Inhibitors of SERT binding are well known as selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, sertraline, paroxetine, and escitalopram, that are commonly prescribed antidepressants. Positron emission tomography (PET) and single photon emission tomography (SPECT) imaging agents targeting SERT may be useful for studying its function and providing a tool for monitoring drug treatment...
July 4, 2018: Nuclear Medicine and Biology
Nina Savisto, Jörgen Bergman, Jussi Aromaa, Sarita Forsback, Olli Eskola, Tapio Viljanen, Johan Rajander, Stefan Johansson, Julian Grigg, Sajinder Luthra, Olof Solin
INTRODUCTION: Production of fluorine-18-labeled radiopharmaceuticals is always associated with the varying levels of the same compound containing stable fluorine-19. In practice, this affects the molar activity (Am ), defined as amount of radioactivity divided by the molar quantity (Bq/mol). We have focused on studying how the material of the transport tubing connecting the cyclotron target chamber to the synthesis device affects the concentration of fluoride in the water arriving to the reaction vessel and subsequently the Am of the fluorine-18 labeled radiopharmaceuticals produced...
June 30, 2018: Nuclear Medicine and Biology
Keisuke Mitsuoka, Aya Kita, Yoshihiro Murakami, Kenna Shirasuna, Akihiro Noda, Kentaro Yamanaka, Naoki Kaneko, Sosuke Miyoshi
INTRODUCTION: Sepantronium bromide (YM155) is a survivin suppressant that induces apoptosis in tumor cells. Although YM155 induces tumor regression in various tumor types in vivo, phase I and II studies demonstrated responding and non-responding patient populations. We investigated 11 C-labeled YM155 ([11 C]YM155) used as a positron emission tomography (PET) tracer to assess whether tumor uptake of [11 C]YM155 correlated with its anti-tumor effect, thereby allowing identification of patients who would respond to YM155 treatment...
June 27, 2018: Nuclear Medicine and Biology
Erik de Blois, Rory M S de Zanger, Elisabeth Oehlke, Ho Sze Chan, Wouter A P Breeman
INTRODUCTION: 68 Ga-radiopharmaceuticals are common in the field of Nuclear Medicine to visualize receptor-mediated processes. In contrast to straightforward labeling procedures for clinical applications, preclinical in vitro and in vivo applications are hampered for reasons like e.g. volume restriction, activity concentration, molar activity and osmolality. Therefore, we developed a semi-automatic system specifically to overcome these problems. A difficulty appeared unexpectedly, as intrinsic trace metals derived from eluate (Zn, Fe and Cu) are concentrated as well in amounts that influence radiochemical yield and thus lower molar activity...
June 27, 2018: Nuclear Medicine and Biology
Nilantha Bandara, Tamila J Stott Reynolds, Rebecca Schehr, Rajendra P Bandari, Philipp J Diebolder, Stephanie Krieger, Jingli Xu, Yubin Miao, Buck E Rogers, Charles J Smith
INTRODUCTION: In this study, we describe development of a true matched-pair theranostic agent that is able to target the αV β3 integrin and the gastrin releasing peptide receptor (GRPR). We herein describe methods to metallate and characterize the new conjugate and to validate its biological efficacy by in vitro and in vivo methods. METHODS: We have previously described the development of [RGD-Glu-6Ahx-RM2] (where RGD: Arg-Gly-Asp; Glu: glutamic acid; 6-Ahx: 6-amino hexanoic acid; RM2: (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2)) that has been conjugated to a DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) bifunctional chelating agent (BFCA) to afford [RGD-Glu-[DO3A]-6-Ahx-RM2] peptide...
July 2018: Nuclear Medicine and Biology
Falguni Basuli, Xiang Zhang, Mark R Williams, Jurgen Seidel, Michael V Green, Peter L Choyke, Rolf E Swenson, Elaine M Jagoda
INTRODUCTION: Equilibrium single-photon radionuclide imaging methods for assessing cardiac function and the integrity of the vascular system have long been in use for both clinical and research purposes. However, positron-emitting blood pool agents that could provide PET equivalents to these (and other) clinical procedures have not yet been adopted despite technical imaging advantages offered by PET. Our goal was to develop a PET blood pool tracer that not only meets necessary in vivo biological requirements but can be produced with an uncomplicated and rapid synthesis method which would facilitate clinical translation...
July 2018: Nuclear Medicine and Biology
Farzaneh Rezazadeh, Nourollah Sadeghzadeh, Seyed Mohammad Abedi, Saeid Abediankenari
INTRODUCTION: The aim of this study was to evaluate the ability of D (LPR), a novel retro-inverso peptidomimetic derivative for imaging colon cancer. METHODS: Two different D (LPR) analogs were designed and compared based on conjugation of HYNIC at peptide's C or N terminal and then labeled with technetium-99m using tricine/EDDA as an exchange coligands. The radiolabeled conjugates were assessed for in vitro stability in saline and serum. The VEGFR-1 and NRP-1 receptors affinity, in vitro internalization and also dissociation Constance was evaluated...
July 2018: Nuclear Medicine and Biology
Jyotsna Bhatt, Archana Mukherjee, Ajit Shinto, Kamaleshwaran Koramadai Karuppusamy, Aruna Korde, Mukesh Kumar, Haladhar Dev Sarma, Krishnamohan Repaka, Ashutosh Dash
INTRODUCTION: Gallium-68 based infection imaging agents are in demand to detect infection foci with high spatial resolution and sensitivity. In this study, Ubiquicidin derived octapeptide, UBI (31-38) conjugated with macrocyclic chelator NOTA was radiolabeled with 68 Ga to develop infection imaging agent. METHODS: Circular dichroism (CD) spectroscopy was performed to study conformational changes in UBI (31-38) and its NOTA conjugate in a "membrane like environment"...
July 2018: Nuclear Medicine and Biology
Frederic Debordeaux, Lucie Chansel-Debordeaux, Jean-Baptiste Pinaquy, Philippe Fernandez, Jurgen Schulz
Non-invasive investigation of integrin expression is an interesting approach in nuclear medicine department. Indeed, integrins are overexpressed in a wide array of diseases, including tumor neoangiogenesis, cardiovascular pathologies, immune dysfunction, etc. Different targets have been identified in order to be detected and quantified for angiogenesis and vascular remodeling, among them VEGF, matrix metalloproteases, and integrins (αv β3 , but also α5 ß1 and αv β6 ). Their targeting appears of great interest either for early diagnosis, aggressiveness staging of the disease or for selection of responders to new-targeted therapies...
July 2018: Nuclear Medicine and Biology
Ganesan Vaidyanathan, Choong Mo Kang, Darryl McDougald, Il Minn, Mary Brummet, Martin G Pomper, Michael R Zalutsky
INTRODUCTION: Radiolabeled, low-molecular-weight prostate-specific membrane antigen (PSMA) inhibitors based on the Glu-ureido pharmacophore show promise for the detection and treatment of castration-resistant prostate cancer; however, high renal retention of activity, related in part to overexpression of PSMA in kidneys can be problematic. The goal of the current study was to investigate the use of brush border enzyme-cleavable linkers as a strategy for reducing kidney activity levels from radiolabeled PSMA inhibitors...
July 2018: Nuclear Medicine and Biology
Ole Tietz, Alison Marshall, Cody Bergman, Melinda Wuest, Frank Wuest
INTRODUCTION: Non-invasive imaging of COX-2 in cancer represents a powerful tool for assessing COX-2-mediated effects on chemoprevention and radiosensitization using potent and selective COX-2 inhibitors as an emerging class of anticancer drugs. Careful assessment of the pharmacokinetic profile of radiolabeled COX-2 inhibitors is of crucial importance for the development of suitable radiotracers for COX-2 imaging in vivo. The delicate balance between the selection of typical COX-2 pharmacophores and the resulting physicochemical characteristics of the COX-2 inhibitor represents a formidable challenge for the search of radiolabeled COX-2 imaging agents...
July 2018: Nuclear Medicine and Biology
Wen Jiang, David Ulmert, Brian W Simons, Diane S Abou, Daniel L J Thorek
INTRODUCTION: Radium-223 dichloride is the first alpha-particle emitting therapeutic agent approved by FDA and EMA for bone metastatic castration-resistant prostate cancer. We studied its age-dependent biodistribution in mice, and compared it with [99m Tc]Tc-MDP and [18 F]NaF aiming to identify a potential imaging surrogate to predict [223 Ra]RaCl2 whole-body localization. METHODS: Male C57Bl/6 mice dosed with [223 Ra]RaCl2 were sacrificed at different time points to explore [223 Ra]RaCl2 whole-body distribution...
July 2018: Nuclear Medicine and Biology
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