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Nuclear Medicine and Biology

Tomoyuki Ohya, Kotaro Nagatsu, Hisashi Suzuki, Masami Fukada, Katsuyuki Minegishi, Masayuki Hanyu, Ming-Rong Zhang
INTRODUCTION: Copper-67 is an attractive beta emitter for targeted radionuclide therapy. However, the availability of67 Cu limits its potential use in a wide range of applications. In this study, we propose an easy small-scale production of67 Cu using64 Ni target for a preclinical study. METHODS: 67 Cu was produced from an electrodeposited64 Ni target via the64 Ni(α, p)67 Cu-reaction with a 36 MeV alpha beam at 15 eμA (electrical microampere) conducted for 7 h...
February 20, 2018: Nuclear Medicine and Biology
Chrysoula Vraka, Monika Dumanic, Teresa Racz, Florian Pichler, Cecile Philippe, Theresa Balber, Eva-Maria Klebermass, Karl-Heinz Wagner, Marcus Hacker, Wolfgang Wadsak, Markus Mitterhauser
In drug development, biomarkers for cerebral applications have a lower success rate compared to cardiovascular drugs or tumor therapeutics. One reason is the missing blood brain barrier penetration, caused by the tracer's interaction with efflux transporters such as the P-gp (MDR1 or ABCB1). Aim of this study was the development of a reliable model to measure the interaction of radiotracers with the human efflux transporter P-gp in parallel to the radiolabeling process. LigandTracer® Technology was used with the wildtype cell line MDCKII and the equivalent cell line overexpressing human P-gp (MDCKII-hMDR1)...
February 14, 2018: Nuclear Medicine and Biology
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
Johan Spetz, Nils Rudqvist, Britta Langen, Toshima Z Parris, Johanna Dalmo, Emil Schüler, Bo Wängberg, Ola Nilsson, Khalil Helou, Eva Forssell-Aronsson
INTRODUCTION: Patients with neuroendocrine tumors expressing somatostatin receptors are often treated with177 Lu-octreotate. Despite being highly effective in animal models,177 Lu-octreotate-based therapies in the clinical setting can be optimized further. The aims of the study were to identify and elucidate possible optimization venues for177 Lu-octreotate tumor therapy by characterizing transcriptional responses in the GOT1 small intestine neuroendocrine tumor model in nude mice. METHODS: GOT1-bearing female BALB/c nude mice were intravenously injected with 15 MBq177 Lu-octreotate (non-curative amount) or mock-treated with saline solution...
February 6, 2018: Nuclear Medicine and Biology
B V Egorova, E V Matazova, A A Mitrofanov, G Yu Aleshin, A L Trigub, A D Zubenko, O A Fedorova, Yu V Fedorov, S N Kalmykov
No abstract text is available yet for this article.
February 6, 2018: Nuclear Medicine and Biology
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 with18 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...
February 2, 2018: Nuclear Medicine and Biology
Alejandro Amor-Coarasa, James Kelly, Shashikanth Ponnala, Yogindra Vedvyas, Anastasia Nikolopoulou, Clarence Williams, Moonsoo M Jin, J David Warren, John W Babich
INTRODUCTION: CXCR4 specific [18 F]-labeled positron emission tomography (PET) imaging agents are needed which would enable general distribution of the radiotracer for clinical investigation. We sought to synthesize, radiolabel and evaluate [18 F]RPS-544, a novel non-peptide CXCR4 antagonist as a CXCR4 specific probe. We compared [18 F]RPS-544 with the previously published [18 F]-3 ([18 F]RPS-510 in this paper) in a bi-lateral tumor model of differential CXCR4 expression for its ability to selectively target CXCR4 expression...
January 31, 2018: Nuclear Medicine and Biology
Nariman Nezami, Nima Kokabi, Juan C Camacho, David M Schuster, Minzhi Xing, Hyun S Kim
INTRODUCTION: There are two different types of Y90 Microspheres, glass and resin, in the market for Y90 radioembolization (Y90-RE). This study aimed to investigate the dose of radiation delivered through glass vs. resin-based Y90-RE to intrahepatic cholangiocarcinoma (ICC). METHODS: In this retrospective study, 10 patients with ICC underwent Y90-RE, five underwent glass (Glass group) and other 5 resin (Resin group) microspheres. Technetium-99m macro-aggregated albumin (Tc-99m MAA) shunt study was performed two weeks before Y90-RE...
January 16, 2018: Nuclear Medicine and Biology
Wen Jing Zhu, Masato Kobayashi, Kohei Yamada, Kodai Nishi, Kotaro Takahashi, Asuka Mizutani, Ryuichi Nishii, Leo G Flores, Naoto Shikano, Munetaka Kunishima, Keiichi Kawai
INTRODUCTION: Due to its poor prognosis, specific imaging for early detection of malignant melanoma is strongly desired. Although radioiodine-labeled 4-hydroxyphenylcysteamine, which we previously developed, has good affinity for tyrosinase, an enzyme in the melanin metabolic pathway, image contrast of the melanoma:organ ratios is not sufficiently high for detection of primary melanoma and metastases at early injection times. In this study, we developed radioiodine-labeled acetaminophen (I-AP) for specific, high-contrast imaging of malignant melanoma...
January 3, 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...
December 27, 2017: Nuclear Medicine and Biology
Hailey A Houson, Gregory N Nkepang, Andria F Hedrick, Vibhudutta Awasthi
Positron emission tomography (PET) of myocardial infarction (MI) by infarct avid imaging has the potential to reduce the time to diagnosis and improve diagnostic accuracy. The objective of this work was to synthesize 18 F-labeled glucaric acid (FGA) for PET imaging of isoproterenol-induced cardiomyopathy in a rat model. METHODS: We synthesized 18 F-FGA by controlled oxidation of 18 F-fluorodeoxy glucose (FDG), mediated by 4-acetamido-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) in presence of NaBr and NaOCl in highly-buffered reaction conditions...
December 27, 2017: Nuclear Medicine and Biology
Michael Wagner, Melinda Wuest, Ingrit Hamann, Ana Lopez-Campistrous, Todd P W McMullen, Frank Wuest
INTRODUCTION: Receptor tyrosine kinase (RTK) platelet-derived growth factor receptor-alpha (PDGFRα) was recently identified as a molecular switch for dedifferentiation in thyroid cancer that predicts resistance to therapy as well as recurrence of disease in papillary thyroid cancer. Here we describe the radiolabeling and functional characterization of an imaging probe based on a PDGFRα-specific monoclonal antibody (mAb) for immuno-PET imaging of PDGFRα in papillary thyroid cancer. METHODS: Antibody D13C6 (Cell Signaling) was decorated with chelator NOTA using bioconjugation reaction with 2-(p-NCS-Bz)-NOTA...
December 27, 2017: Nuclear Medicine and Biology
Malgorzata Lipowska, Nashwa Jarkas, Ronald J Voll, Jonathon A Nye, Jeffrey Klenc, Mark M Goodman, Andrew T Taylor
INTRODUCTION: Our previous work demonstrated that the 99mTc renal tracer, 99mTc(CO)3(FEDA) (99mTc-1), has a rapid clearance comparable in rats to that of 131I-OIH, the radioactive gold standard for the measurement of effective renal plasma flow. The uncharged fluoroethyl pendant group of 99mTc-1 provides a route to the synthesis of a structurally analogous rhenium-tricarbonyl 18F renal imaging agent, Re(CO)3([18F]FEDA) (18F-1). Our goal was to develop an efficient one-step method for the preparation of 18F-1 and to compare its pharmacokinetic properties with those of 131I-OIH in rats...
December 27, 2017: Nuclear Medicine and Biology
Chrysoula Vraka, Sanja Mijailovic, Vanessa Fröhlich, Markus Zeilinger, Eva-Maria Klebermass, Wolfgang Wadsak, Karl-Heinz Wagner, Marcus Hacker, Markus Mitterhauser
INTRODUCTION: Due to the high candidate exclusion rate during a drug development process, an early prediction of the pharmacokinetic behavior would be needed. Accordingly, high performance bioaffinity chromatography (HPBAC) approaches are growing in popularity, however, there is a lack of knowledge and no consensus about the relation between HPBAC measurements, in vivo distribution and blood brain barrier (BBB) penetration behavior. With respect to radiotracers, there is almost no reference data available for plasma protein binding (PPB), permeability (Pm) and the membrane coefficient (KIAM )...
March 2018: Nuclear Medicine and Biology
Georgios Paparidis, Melpomeni Akrivou, Vicky Tsachouridou, Antonio Shegani, Ioannis S Vizirianakis, Ioannis Pirmettis, Minas S Papadopoulos, Dionysia Papagiannopoulou
INTRODUCTION: Lipophilic delocalized cations accumulate in tumor cell mitochondria due to their higher transmembrane potential. In this work, this strategy was adopted for the development of99m Tc tumor-targeted imaging agents. METHODS: Two tridentate ligands containing the triphenylphosphonium cation, L1 (S-cysteinyl) and L2 (N-iminodiacetate) as well as the respective99m Tc/ReL1 and99m Tc/ReL2 tricarbonyl complexes were synthesized. The effect of the ligands and the Re complexes on cell growth in U-87 MG glioblastoma cells was assessed...
February 2018: Nuclear Medicine and Biology
Lukas Nics, Britta Steiner, Eva-Maria Klebermass, Cecile Philippe, Markus Mitterhauser, Marcus Hacker, Wolfgang Wadsak
INTRODUCTION: The decision whether an in-house produced short-lived radiopharmaceutical can be applied in-vivo is based on (1) the fulfilment of all quality criteria; (2) the availability of enough radioactivity for subsequent imaging; and (3) a molar activity (MA) above the set limits to guarantee safe administration without competing occupancy of the non-radioactive compound; and (4) an activity concentration, which is high enough for the application in certain preclinical studies. Hence, time reduction can be of major importance to increase final product yields, MA and activity concentrations...
February 2018: Nuclear Medicine and Biology
Hyosook Hwang, Kwang Il Kim, JeongIl Kwon, Byoung Soo Kim, Hwan-Seok Jeong, Su Jin Jang, Phil-Sun Oh, Ho Sung Park, Seok Tae Lim, Myung-Hee Sohn, Hwan-Jeong Jeong
No abstract text is available yet for this article.
February 2018: Nuclear Medicine and Biology
Erika V Almeida, Samuel L De Brito
INTRODUCTION: Complexes of technetium-99m (99mTc) with meso-dimercaptosuccinic acid (DMSA) have been widely used as diagnostic agents in nuclear medicine. The degradation products (DP) of DMSA formed under different forced conditions have been identified through HPLC-DAD and LC-MSn studies. In this study, the DMSA kit was subjected to forced degradation under hydrolysis conditions as prescribed by the International Conference on Harmonization (ICH) guideline Q1A. METHODS: Chromatographic separation was accomplished on a reverse phase Shim-Pack VP-ODS (150 mm × 4...
February 2018: Nuclear Medicine and Biology
Vladimir Stepanov, Akihiro Takano, Ryuji Nakao, Nahid Amini, Shotaro Miura, Tomoaki Hasui, Haruhide Kimura, Takahiko Taniguchi, Christer Halldin
INTRODUCTION: Phosphodiesterase 10A (PDE10A) is a member of the PDE enzyme family that degrades cyclic adenosine and guanosine monophosphates (cAMP and cGMP). Based on the successful development of [11 C]T-773 as PDE10A positron emission tomography (PET) radioligand, in this study our aim was to develop and evaluate fluorine-18 analogs of [11 C]T-773. METHODS: [18 F]FM-T-773-d2 and [18 F]FE-T-773-d4 were synthesized from the same precursor used for11 C-labeling of T-773 in a two-step approach via18 F-fluoromethylation and18 F-fluoroethylation, respectively, using corresponding deuterated synthons...
February 2018: Nuclear Medicine and Biology
Martin Prause, Sabrina Niedermoser, Carmen Wängler, Clemens Decristoforo, Uwe Seibold, Stephanie Riester, Takahiro Taguchi, Ralf Schirrmacher, Gert Fricker, Björn Wängler
INTRODUCTION: Gastrointestinal stromal tumors (GIST) have a wide range of mutations, but can mostly be treated with Imatinib, until eventually resistance towards this tyrosine kinase inhibitor is acquired. Early and non-invasive determination of the sensitivity of the tumor and its metastases towards Imatinib by positron emission tomography (PET) would be beneficial for therapy planning and monitoring. METHODS: We developed a synthesis strategy towards the precursor molecule, performed the18 F-synthesis and in the following evaluated the radioligand in vitro regarding its lipophilicity, stability and biological activity (KIT binding properties) as well as its in vivo properties in GIST tumor-bearing mice...
February 2018: Nuclear Medicine and Biology
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