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Molecular Imaging

Masaru Ishihara, Masahisa Onoguchi, Takayuki Shibutani
The aim of this study was to assess the washout rate (WOR) for thallium-201-chloride single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) using cadmium zinc telluride detectors for SPECT (CZT SPECT) versus conventional Anger-type SPECT (conventional SPECT). A total of 52 Japanese patients were examined using CZT SPECT and conventional SPECT, and the global WORs were compared. Additionally, the MPI WORs were compared for patients with a normal MPI versus those in whom MPI reflected the patients' multivessel disease (MVD) MPI...
January 2018: Molecular Imaging
Kambiz Rahbar, Ali Afshar-Oromieh, Hossein Jadvar, Hojjat Ahmadzadehfar
Prostate-specific membrane antigen (PSMA) is a promising target for imaging diagnostics and targeted radionuclide therapy (theranostics) of prostate cancer and its metastases. There is increasing evidence of encouraging response rates and a low toxicity profile of radioligand therapy (RLT) of metastatic castration-resistant prostate cancer using 177 Lu-labeled PSMA ligands. In this article, we review the current status of diagnostics and therapy using radiolabeled PSMA ligands. We also suggest protocols for patient selection criteria and conduct of PSMA-based RLT...
January 2018: Molecular Imaging
Yongfeng Zhao, Bo Pang, Lisa Detering, Hannah Luehmann, Miaoxin Yang, Kvar Black, Deborah Sultan, Younan Xia, Yongjian Liu
PURPOSE: Melanoma is a lethal skin cancer with unmet clinical needs for targeted imaging and therapy. Nanoscale materials conjugated with targeting components have shown great potential to improve tumor delivery efficiency while minimizing undesirable side effects in vivo. Herein, we proposed to develop targeted nanoparticles for melanoma theranostics. METHOD: In this work, gold nanocages (AuNCs) were conjugated with α-melanocyte-stimulating hormone (α-MSH) peptide and radiolabeled with 64 Cu for melanocortin 1 receptor-(MC1R) targeted positron emission tomography (PET) in a mouse B16/F10 melanoma model...
January 2018: Molecular Imaging
Govindarajan Srimathveeravalli, Dalya Abdel-Atti, Carlos Pérez-Medina, Haruyuki Takaki, Stephen B Solomon, Willem J M Mulder, Thomas Reiner
Reversible electroporation (RE) can facilitate nanoparticle delivery to tumors through direct transfection and from changes in vascular permeability. We investigated a radiolabeled liposomal nanoparticle (89 Zr-NRep) for monitoring RE-mediated liposomal doxorubicin (DOX) delivery in mouse tumors. Intravenously delivered 89 Zr-NRep allowed positron emission tomography imaging of electroporation-mediated nanoparticle uptake. The relative order of 89 Zr-NRep injection and electroporation did not result in significantly different overall tumor uptake, suggesting direct transfection and vascular permeability can independently mediate deposition of 89 Zr-NRep in tumors...
January 2018: Molecular Imaging
Adriana V F Massicano, Bernadette V Marquez-Nostra, Suzanne E Lapi
Since its discovery, the human epidermal growth factor 2 (HER2) has been extensively studied. Presently, there are 2 standard diagnostic techniques to assess HER2 status in biopsies: immunohistochemistry and fluorescence in situ hybridization. While these techniques have played an important role in the treatment of patients with HER2-positive cancer, they both require invasive biopsies for analysis. Moreover, the expression of HER2 is heterogeneous in breast cancer and can change over the course of the disease...
January 2018: Molecular Imaging
Andrew W Stephens, Norman Koglin, Ludger M Dinkelborg
Thrombus formation can lead to heart attacks, stroke and pulmonary embolism, which are major causes of mortality. Current standard diagnostic imaging methods detect anatomic abnormalities such as vascular flow impairment but have limitations. By using a targeted molecular imaging approach critical components of a pathology can be selectively visualized and exploited for an improved diagnosis and patient management. The GPIIb/IIIa receptor is abundantly and specifically exposed on activated platelets and is the key receptor in thrombus formation...
January 2018: Molecular Imaging
Su Xu, Wenjun Zhu, Yamin Wan, JiaBei Wang, Xi Chen, Liya Pi, Mary Kay Lobo, Bin Ren, Zhekang Ying, Michael Morris, Qi Cao
Minimal hepatic encephalopathy (MHE) is highly prevalent, observed in up to 80% of patients with liver dysfunction. Minimal hepatic encephalopathy is defined as hepatic encephalopathy with cognitive deficits and no grossly evident neurologic abnormalities. Clinical management may be delayed due to the lack of in vivo quantitative methods needed to reveal changes in brain neurobiochemical biomarkers. To gain insight into the development of alcoholic liver disease-induced neurological dysfunction (NDF), a mouse model of late-stage alcoholic liver fibrosis (LALF) was used to investigate changes in neurochemical levels in the thalamus and hippocampus that relate to behavioral changes...
January 2018: Molecular Imaging
Stephen M Chrzanowski, Ravneet S Vohra, Brittany A Lee-McMullen, Abhinandan Batra, Ray A Spradlin, Jazmine Morales, Sean Forbes, Krista Vandenborne, Elisabeth R Barton, Glenn A Walter
Assessment of muscle pathology is a key outcome measure to measure the success of clinical trials studying muscular dystrophies; however, few robust minimally invasive measures exist. Indocyanine green (ICG)-enhanced near-infrared (NIR) optical imaging offers an objective, minimally invasive, and longitudinal modality that can quantify pathology within muscle by imaging uptake of ICG into the damaged muscles. Dystrophic mice lacking dystrophin (mdx) or gamma-sarcoglycan (Sgcg-/- ) were compared to control mice by NIR optical imaging and magnetic resonance imaging (MRI)...
January 2017: Molecular Imaging
Bok-Nam Park, Su Jin Lee, Jung Hyun Roh, Kyung-Han Lee, Young-Sil An, Joon-Kee Yoon
INTRODUCTION: The potential of a radioiodine-labeled, anti-adenosine triphosphate synthase monoclonal antibody (ATPS mAb) as a theragnostic agent for simultaneous cancer imaging and treatment was evaluated. METHODS: Adenosine triphosphate synthase monoclonal antibody was labeled with radioiodine, then radiotracer uptake was measured in 6 different cancer cell lines. In vivo biodistribution was evaluated 24 and 48 hours after intravenous injection of125 I-ATPS mAb into MKN-45 tumor-bearing mice (n = 3)...
January 2017: Molecular Imaging
Chengcheng Zhang, Kuo-Shyan Lin, François Bénard
Melanoma is a deadly disease at late metastatic stage, and early diagnosis and accurate staging remain the key aspects for managing melanoma. The melanocortin 1 receptor (MC1 R) is overexpressed in primary and metastatic melanomas, and its endogenous ligand, the α-melanocyte-stimulating hormone (αMSH), has been extensively studied for the development of MC1 R-targeted molecular imaging and therapy of melanoma. Natural αMSH is not well suited for this purpose due to low stability in vivo. Unnatural amino acid substitutions substantially stabilized the peptide, while cyclization via lactam bridge and metal coordination further improved binding affinity and stability...
January 2017: Molecular Imaging
Spencer C Behr, Brett J Mollard, Jaewon Yang, Robert R Flavell, Randall A Hawkins, Youngho Seo
Recent technical advances in positron emission tomography/magnetic resonance imaging (PET/MRI) technology allow much improved time-of-flight (TOF) and regularized iterative PET reconstruction regularized iterative reconstruction (RIR) algorithms. We evaluated the effect of TOF and RIR on standardized uptake values (maximum and peak SUV [SUVmax and SUVpeak ]) and their metabolic tumor volume dependencies and visual image quality for18 F-fluorocholine PET/MRI in patients with newly diagnosed prostate cancer. Fourteen patients were administered with 3 MBq/kg of18 F-fluorocholine and scanned dynamically for 30 minutes...
January 2017: Molecular Imaging
Yingying Sun, Xilin Sun, Baozhong Shen
The important role of insulin-like growth factor 1 receptor (IGF-1R) in malignant tumors has been well established. Increased IGF-1R activity promotes cancer cell proliferation, migration, and invasion and is associated with tumor metastasis, treatment resistance, poor prognosis, and shortened survival in patients with cancer. However, while IGF-1R has become a promising target for cancer therapy, IGF-1R-targeted therapy is ineffective in unselected patients. It is therefore essential to evaluate IGF-1R expression before treatment in order to identify responsive patients, monitor therapy efficacy, and estimate prognosis...
January 2017: Molecular Imaging
Eleni Gourni, Luigi Del Pozzo, Mark Bartholomä, Yvonne Kiefer, Philipp T Meyer, Helmut R Maecke, Jason P Holland
Radiotracers incorporating the urea-based Glu-NH-C(O)-NH-Lys group have gained prominence due to their role in targeting prostate-specific membrane antigen (PSMA)-a clinical biomarker of prostate cancer. Here, the synthesis, radiolabeling, and in vitro and in vivo characterization of two68 Ga-radiolabeled Glu-NH-C(O)-NH-Lys radiotracers conjugated to the desferrioxamine B (DFO) chelate were evaluated. Two linker groups based on amide bond and thiourea coupling chemistries were employed to develop68 Ga-DFO-Nsucc-PSMA (68 Ga-4) and68 Ga-DFO- pNCS-Bn-PSMA (68 Ga-7), respectively...
January 2017: Molecular Imaging
Nana L Christensen, Steen Jakobsen, Anna C Schacht, Ole L Munk, Aage K O Alstrup, Lars P Tolbod, Hendrik J Harms, Søren Nielsen, Lars C Gormsen
INTRODUCTION: Despite the decades long use of [(11)C]palmitate positron emission tomography (PET)/computed tomography in basic metabolism studies, only personal communications regarding dosimetry and biodistribution data have been published. METHODS: Dosimetry and biodistribution studies were performed in 2 pigs and 2 healthy volunteers by whole-body [(11)C]palmitate PET scans. Metabolite studies were performed in 40 participants (healthy and with type 2 diabetes) under basal and hyperinsulinemic conditions...
January 2017: Molecular Imaging
T Lee Collier, Kevin P Maresca, Marc D Normandin, Paul Richardson, Timothy J McCarthy, Steven H Liang, Rikki N Waterhouse, Neil Vasdev
The Massachusetts General Hospital Radiochemistry Program, in collaboration with Pfizer, has developed unique 11 C and 18 F-labeling strategies to synthesize isotopologs of lorlatinib (PF-06463922) which is undergoing phase III clinical trial investigations for treatment of non-small-cell lung cancers with specific molecular alterations. A major goal in cancer therapeutics is to measure the concentrations of this drug in the brain metastases of patients with lung cancer, and penetration of the blood-brain barrier is important for optimal therapeutic outcomes...
January 2017: Molecular Imaging
Richard Laforest, Farrokh Dehdashti, Yongjian Liu, Jennifer Frye, Sarah Frye, Hannah Luehmann, Deborah Sultan, Joseph S Shan, Bruce D Freimark, Barry A Siegel
PURPOSE: PGN650 is a F(ab')2 antibody fragment that targets phosphatidylserine (PS), a marker normally absent that becomes exposed on tumor cells and tumor vasculature in response to oxidative stress and increases in response to therapy. PGN650 was labeled with124 I to create a positron emission tomography (PET) agent as an in vivo biomarker for tumor microenvironment and response to therapy. In this phase 0 study, we evaluated the pharmacokinetics, safety, radiation dosimetry, and tumor targeting of this tracer in a cohort of patients with cancer...
January 2017: Molecular Imaging
Taiki Magome, Jerry Froelich, Shernan G Holtan, Yutaka Takahashi, Michael R Verneris, Keenan Brown, Kathryn Dusenbery, Jeffrey Wong, Susanta K Hui
This report describes a multimodal whole-body 3'-deoxy-3'[(18)F]-fluorothymidine positron emission tomography (FLT-PET) and dual-energy computed tomography (DECT) method to identify leukemia distribution within the bone marrow environment (BME) and to develop disease- and/or BME-specific radiation strategies. A control participant and a newly diagnosed patient with acute myeloid leukemia prior to induction chemotherapy were scanned with FLT-PET and DECT. The red marrow (RM) and yellow marrow (YM) of the BME were segmented from DECT using a basis material decomposition method...
January 2017: Molecular Imaging
Shu-Fei Lin, Frederic Bois, Daniel Holden, Nabeel Nabulsi, Richard Pracitto, Hong Gao, Michael Kapinos, Jo-Ku Teng, Anupama Shirali, Jim Ropchan, Richard E Carson, Charles S Elmore, Neil Vasdev, Yiyun Huang
The myriad physiological functions of γ-amino butyric acid (GABA) are mediated by the GABA-benzodiazepine receptor complex comprising of the GABAA , GABAB , and GABAC groups. The various GABAA subunits with region-specific distributions in the brain subserve different functional and physiological roles. For example, the sedative and anticonvulsive effects of classical benzodiazepines are attributed to the α1 subunit, and the α2 and α3 subunits mediate the anxiolytic effect. To optimize pharmacotherapies with improved efficacy and devoid of undesirable side effects for the treatment of anxiety disorders, subtype-selective imaging radiotracers are required to assess target engagement at GABA sites and determine the dose-receptor occupancy relationships...
January 2017: Molecular Imaging
Heike E Daldrup-Link
This invited commentary discusses a recent article by Mohanty et al in Molecular Cancer Therapeutics about significant therapeutic efficacies of novel theranostic nanoparticles (TNPs) for the treatment of human brain cancers in mouse models. The TNPs were cleaved by enzymes in the tumor tissue, matrix metalloproteinase (MMP-14), which lead to release of a highly potent therapeutic drug, azademethylcolchicine. Data showed that the TNPs caused selective toxic effects in MMP-14-expressing glioblastoma and not normal brain...
January 2017: Molecular Imaging
Brian P Rempel, Eric W Price, Christopher P Phenix
Hydrolytic enzymes are a large class of biological catalysts that play a vital role in a plethora of critical biochemical processes required to maintain human health. However, the expression and/or activity of these important enzymes can change in many different diseases and therefore represent exciting targets for the development of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) radiotracers. This review focuses on recently reported radiolabeled substrates, reversible inhibitors, and irreversible inhibitors investigated as PET and SPECT tracers for imaging hydrolytic enzymes...
January 2017: Molecular Imaging
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