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"small animal PET"

Tilman Läppchen, Jason P Holland, Yvonne Kiefer, Mark D Bartholomä
Background: We recently developed a chelating platform based on the macrocycle 1,4,7-triazacyclononane with up to three, five-membered azaheterocyclic arms for the development of 68 Ga- and 64 Cu-based radiopharmaceuticals. Here, a 68 Ga-labelled conjugate comprising the bifunctional chelator NODIA-Me in combination with the αv ß3 -targeting peptide c(RGDfK) has been synthesized and characterized. The primary aim was to evaluate further the potential of our NODIA-Me chelating system for the development of 68 Ga-labelled radiotracers...
2018: EJNMMI Radiopharmacy and Chemistry
Yan Xing, Tiantian Wang, Lilei Guo, Na Sun, Jinhua Zhao
Non-small cell lung cancer (NSCLC) accounts for more than 80% of lung cancer. Nowadays, gemcitabine and cisplatin in combination have been adopted as the first-line chemotherapy for patients with NSCLC. This study aimed to monitor early response to combined chemotherapy of gemcitabine plus cisplatin in a mouse model of NSCLC by using 18 F-fluorodeoxyglucose and 18 F-fluorothymidine small animal positron emission tomography (PET). Lewis lung carcinoma-bearing C57BL/6 mice were treated with gemcitabine-cisplatin or saline...
June 1, 2017: Sheng Wu Yi Xue Gong Cheng Xue za Zhi, Journal of Biomedical Engineering, Shengwu Yixue Gongchengxue Zazhi
Corinne Beinat, Tom Haywood, Yun-Sheng Chen, Chirag B Patel, Israt S Alam, Surya Murty, Sanjiv Sam Gambhir
PURPOSE: There is a strong, unmet need for superior positron emission tomography (PET) imaging agents that are able to measure biochemical processes specific to prostate cancer. Pyruvate kinase M2 (PKM2) catalyzes the concluding step in glycolysis and is a key regulator of tumor growth and metabolism. Elevation of PKM2 expression was detected in Gleason 8-10 tumors compared to Gleason 6-7 carcinomas, indicating that PKM2 may potentially be a marker of aggressive prostate cancer. We have recently reported the development of a PKM2-specific radiopharmaceutical [18 F]DASA-23 and herein describe its evaluation in cell culture and preclinical models of prostate cancer...
May 7, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Hans-Soenke Jans, Xiao-Hong Yang, Dion R Brocks, Piyush Kumar, Melinda Wuest, Leonard I Wiebe
PURPOSE: Pharmacokinetic (PK) data are generally derived from blood samples withdrawn serially over a defined period after dosing. In small animals, blood sampling after dosing presents technical difficulties, particularly when short time intervals and frequent sampling are required. Positron emission tomography (PET) is a non-invasive functional imaging technique that can provide semi-quantitative temporal data for defined volume regions of interest (vROI), to support kinetic analyses in blood and other tissues...
2018: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
Luise Fiedler, Markus Kellner, Rosel Oos, Guido Böning, Sibylle Ziegler, Peter Bartenstein, Reinhard Zeidler, Franz Josef Gildehaus, Simon Lindner
64Cu is a cyclotron-produced radionuclide which offers, due to its characteristic decay scheme the possibility to combine PET investigations with radiotherapy. We evaluated the Alceo sys-tem from Comecer SpA to automatically produce 64Cu for radiolabelling purposes. We established a 64Cu production routine with high yields and radionuclide purity in combination with excellent operator radiation protection. The carbonic anhydrase XII targeting 6A10 antibody fab fragment was successfully radiolabelled with the produced 64Cu and proof of principle small animal PET experiments on mice bearing glioma xenografts were performed...
April 18, 2018: ChemMedChem
Negar Omidvari, Geoffrey Topping, Jorge Cabello, Stephan Paul, Markus Schwaiger, Sibylle I Ziegler
Compromises in the design of a positron emission tomography (PET) insert for a magnetic resonance imaging (MRI) system should minimize the deterioration of image quality in both modalities, particularly when simultaneous demanding acquisitions are performed. In this work, the advantages of using individually read-out crystals with high-gain silicon photomultipliers (SiPMs) were studied with a small animal PET insert for a 7 T MRI system, in which the SiPM charge was transferred to outside the MRI scanner using coaxial cables...
March 27, 2018: Physics in Medicine and Biology
Tilman Läppchen, Yvonne Kiefer, Jason P Holland, Mark D Bartholomä
INTRODUCTION: We recently developed a chelating platform based on the macrocycle 1,4,7-triazacyclononane with up to three five-membered azaheterocyclic arms for complexation of the PET nuclides gallium-68 and copper-64. The main objective of this study was to evaluate the stability and pharmacokinetics of68 Ga- and64 Cu-complexes of the bifunctional chelator NODIA-Me 1 covalently bound to a PSMA targeting vector in vivo. METHODS: NODIA-Me 1 was conjugated to the PSMA targeting Glu-NH-CO-NH-Lys moiety to give the bioconjugate NODIA-Me-NaI-Ahx-PSMA 4...
March 10, 2018: Nuclear Medicine and Biology
Lei Jiang, Dongli Song, Hao Chen, Ao Zhang, Huoqiang Wang, Zhen Cheng
Copper(II) ion (Cu2+ ) is the essential element for numerous pathophysiological processes in vivo. Copper transporter 1 (CTR1) is mainly responsible for maintaining Cu2+ accumulation in cells, which has been found to be over-expressed in inflammatory tissues. Therefore, we explored the potential application of 64 CuCl₂ for PET imaging of inflammation through targeting CTR1. The animal models of H₂O₂ induced muscle inflammation and lipopolysaccaharide induced lung inflammation were successfully established, then imaged by small animal PET (PET/CT) post-injection of 64 CuCl₂, and PET images were quantitatively analyzed...
February 24, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Hanna Napieczynska, Armin Kolb, Prateek Katiyar, Matteo Tonietto, Minhaz Ud-Dean, Ramona Stumm, Kristina Herfert, Carsten Calaminus, Bernd J Pichler
The goal of this study was to validate the use of a magnetic resonance-compatible blood sampler (BS) with the detector system based on lutetium oxyorthosilicate scintillator and avalanche photodiodes for small animal positron emission tomography (PET). Methods: Five rats underwent a 60 min 18 F-FDG study. For each animal, the arterial input function (AIF) was derived from the BS recording, from manual blood sampling (MS) and from the PET image. These AIFs were used for kinetic modelling of the striatum using the two tissue irreversible compartment model...
February 23, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Julie Bolcaen, Benedicte Descamps, Tom Boterberg, Christian Vanhove, Ingeborg Goethals
For decades, small animal radiation research was mostly performed using fairly crude experimental setups applying simple single-beam techniques without the ability to target a specific or well-delineated tumor volume. The delivery of radiation was achieved using fixed radiation sources or linear accelerators producing megavoltage (MV) X-rays. These devices are unable to achieve sub-millimeter precision required for small animals. Furthermore, the high doses delivered to healthy surrounding tissue hamper response assessment...
December 28, 2017: Journal of Visualized Experiments: JoVE
Severin Mairinger, Viktoria Zoufal, Thomas Wanek, Alexander Traxl, Thomas Filip, Michael Sauberer, Johann Stanek, Claudia Kuntner, Jens Pahnke, Markus Müller, Oliver Langer
Ko143 is a reference inhibitor of the adenosine triphosphate-binding cassette (ABC) transporter breast cancer resistance protein (humans: ABCG2, rodents: Abcg2) for in vitro and in vivo use. Previous in vitro data indicate that Ko143 binds specifically to ABCG2/Abcg2, suggesting a potential utility of Ko143 as a positron emission tomography (PET) tracer to assess the density (abundance) of ABCG2 in different tissues. In this work we radiolabeled Ko143 with carbon-11 (11 C) and performed small-animal PET experiments with [11 C]Ko143 in wild-type, Abcg2(-/-) , Abcb1a/b(-/-) and Abcb1a/b(-/-) Abcg2(-/-) mice to assess the influence of Abcg2 and Abcb1a/b on tissue distribution and excretion of [11 C]Ko143...
March 30, 2018: European Journal of Pharmaceutical Sciences
Jacobo Cal-Gonzalez, Juan José Vaquero, Joaquín L Herraiz, Mailyn Pérez-Liva, María Luisa Soto-Montenegro, Santiago Peña-Zalbidea, Manuel Desco, José Manuel Udías
PURPOSE: Image quality of positron emission tomography (PET) tracers that emits high-energy positrons, such as Ga-68, Rb-82, or I-124, is significantly affected by positron range (PR) effects. PR effects are especially important in small animal PET studies, since they can limit spatial resolution and quantitative accuracy of the images. Since generators accessibility has made Ga-68 tracers wide available, the aim of this study is to show how the quantitative results of [68 Ga]DOTA-labeled PET/X-ray computed tomography (CT) imaging of neuroendocrine tumors in mice can be improved using positron range correction (PRC)...
January 19, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Ralf S Eschbach, Philipp M Kazmierczak, Maurice M Heimer, Andrei Todica, Heidrun Hirner-Eppeneder, Moritz J Schneider, Georg Keinrath, Olga Solyanik, Jessica Olivier, Wolfgang G Kunz, Maximilian F Reiser, Peter Bartenstein, Jens Ricke, Clemens C Cyran
BACKGROUND: The purpose of the study was to investigate a novel BRAF and CDK 4/6 inhibitor combination therapy in a murine model of BRAF-V600-mutant human melanoma monitored by 18 F-FDG-PET/CT and diffusion-weighted MRI (DW-MRI). METHODS: Human BRAF-V600-mutant melanoma (A375) xenograft-bearing balb/c nude mice (n = 21) were imaged by 18 F-FDG-PET/CT and DW-MRI before (day 0) and after (day 7) a 1-week BRAF and CDK 4/6 inhibitor combination therapy (n = 12; dabrafenib, 20 mg/kg/d; ribociclib, 100 mg/kg/d) or placebo (n = 9)...
January 18, 2018: Cancer Imaging: the Official Publication of the International Cancer Imaging Society
Hiroyuki Kimura, Yu Ogawa, Hiroyuki Fujimoto, Eri Mukai, Hidekazu Kawashima, Kenji Arimitsu, Kentaro Toyoda, Naotaka Fujita, Yusuke Yagi, Keita Hamamatsu, Takaaki Murakami, Atsushi Murakami, Masahiro Ono, Yuji Nakamoto, Kaori Togashi, Nobuya Inagaki, Hideo Saji
β-cell mass (BCM) is known to be decreased in subjects with type-2 diabetes (T2D). Quantitative analysis for BCM would be useful for understanding how T2D progresses and how BCM affects treatment efficacy and for earlier diagnosis of T2D and development of new therapeutic strategies. However, a noninvasive method to measure BCM has not yet been developed. We developed four18 F-labeled exendin(9-39) derivatives for β-cell imaging by PET: [18 F]FB9-Ex(9-39), [18 F]FB12-Ex(9-39), [18 F]FB27-Ex(9-39), and [18 F]FB40-Ex(9-39)...
January 15, 2018: Bioorganic & Medicinal Chemistry
Rudolf Werner, Hiroshi Wakabayashi, Xinyu Chen, Mitsuru Hirano, Tetsuya Shinaji, Constantin Lapa, Steven P Rowe, Mehrbod S Javadi, Takahiro Higuchi
Background: Precise regional quantitative assessment of renal function is limited with conventional99m Tc-labeled renal radiotracers. A recent study reported that the positron emission tomography (PET) radiotracer 2-deoxy-2-18 F-fluorosorbitol (18 F-FDS) has ideal pharmacokinetics for functional renal imaging. Furthermore,18 F-FDS is available via simple reduction from routinely used 2-deoxy-2-18 F-fluoro-D-glucose (18 F-FDG). We aimed to further investigate the potential of18 F-FDS PET as a functional renal imaging agent using rat models of kidney diseases...
December 14, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Zhonghua Kuang, Ziru Sang, Xiaohui Wang, Xin Fu, Ning Ren, Xianming Zhang, Yunfei Zheng, Qian Yang, Zhanli Hu, Junwei Du, Dong Liang, Xin Liu, Hairong Zheng, Yongfeng Yang
PURPOSE: The performance of current small animal PET scanners is mainly limited by the detector performance and depth encoding detectors are required to develop PET scanner to simultaneously achieve high spatial resolution and high sensitivity. Among all depth encoding PET detector approaches, dual-ended readout detector has the advantage to achieve the highest depth of interaction (DOI) resolution and spatial resolution. Silicon photomultiplier (SiPM) is believed to be the photodetector of the future for PET detector due to its excellent properties as compared to the traditional photodetectors such as photomultiplier tube (PMT) and avalanche photodiode (APD)...
February 2018: Medical Physics
Onseok Lee, Jaeyoung Kim, Chilhwan Oh
The purpose of this study was to establish a small-animal model for molecular imaging and to acquire basic data on assessing the efficacy of candidate melanoma drugs using small-animal PET imaging analysis with [18 F]FHBG for herpes simplex virus 1-thymidine kinase (HSV1-tk) gene expression in a melanoma mouse model. The B16 melanoma cell line was transduced with a recombinant lentiviral vector containing the HSV1-tk gene and inoculated into the back skin of C57BL/6J mice. [18 F]FHBG PET imaging showed better contrast for HSV1-tk(+) melanomas compared to brain, heart, gall bladder, intestine and kidney than did [18 F]FDG PET imaging...
February 2018: Experimental Dermatology
Constantin Lapa, Paula Arias-Loza, Nobuyuki Hayakawa, Hiroshi Wakabayashi, Rudolf A Werner, Xinyu Chen, Tetsuya Shinaji, Ken Herrmann, Theo Pelzer, Takahiro Higuchi
Brown adipose tissue (BAT) is an attractive therapeutic target to combat diabetes and obesity due to its ability to increase glucose expenditure. In a genetic rat model (ZDF fa/fa) of type-2 diabetes and obesity, we aimed to investigate glucose utilization of BAT by18 F-FDG PET imaging. Male Zucker diabetic fatty (ZDF) and Male Zucker lean (ZL) control rats were studied at 13 weeks. Three weeks prior to imaging, ZDF rats were randomized into a no-restriction (ZDF-ND) and a mild calorie restriction (ZDF-CR) group...
December 1, 2017: Scientific Reports
Akram Mohammadi, Eiji Yoshida, Fumihiko Nishikido, Munetaka Nitta, Keiji Shimizu, Toshiaki Sakai, Taiga Yamaya
Depth of interaction (DOI) information is indispensable to improving the sensitivity and spatial resolution of positron emission tomography (PET) systems, especially for small field-of-view PET such as small animal PET and human brain PET. We have already developed a series of X'tal cube detectors for isotropic spatial resolution and we obtained the best isotropic resolution of 0.77 mm for detectors with six-sided readout. However, it is still challenging to apply the detector for PET systems due to the high cost of six-sided readout electronics and carrying out segmentation of a monolithic cubic scintillator in three dimensions using the subsurface laser engraving (SSLE) technique...
January 11, 2018: Physics in Medicine and Biology
Nematallah Mansour, Michel Paquette, Samia Ait-Mohand, Véronique Dumulon-Perreault, Brigitte Guérin
INTRODUCTION: Gastrin releasing peptide receptors (GRPRs) are significantly over-expressed on a large proportion of prostate cancers making them prime candidates for receptor-mediated nuclear imaging by PET. Recently, we synthesized a novel bifunctional chelator (BFC) bearing hydroxamic acid arms (DOTHA2 ). Here we investigated the potential of a novel DOTHA2 -conjugated, 64 Cu-radiolabeled GRPR peptide antagonist, [D-Phe6 -Sta13 -Leu14 -NH2 ]bombesin(6-14) (DOTHA2 -PEG-RM26) to visualize prostate tumors by PET imaging...
January 2018: Nuclear Medicine and Biology
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