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ImmunoPET

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https://www.readbyqxmd.com/read/28713886/a-new-tetrapodal-3-hydroxy-4-pyridinone-ligand-for-complexation-of-89-zirconium-for-positron-emission-tomography-pet-imaging
#1
Christian Buchwalder, Cristina Rodríguez-Rodríguez, Paul Schaffer, Stoyan K Karagiozov, Katayoun Saatchi, Urs O Häfeli
Zirconium-89 ((89)Zr) is an ideal radiometal isotope for antibody-based positron emission tomography (immunoPET) as its physical half-life (3.27 days) is a good match with the biological half-life of larger molecular weight targeting molecules, such as antibodies (3-4 days), and its positron emission (BR = 100% EC/β(+), Eβ(+),avg = 395.5 keV) is suited for high resolution PET imaging. Concerns over the in vivo stability of the most commonly used (89)Zr-chelator, desferrioxamine B (DFO), have spurred efforts into the development of alternative (89)Zr-chelators that withstand the release of osteophilic (89)Zr(4+)...
July 17, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28665620/multifunctional-desferrichrome-analogues-as-versatile-89-zr-iv-chelators-for-immunopet-probe-development
#2
Casey J Adams, Justin J Wilson, Eszter Boros
New bifunctional hexa- and octadentate analogues of the hydroxamate-containing siderophore desferrichrome (DFC) have been synthesized and evaluated as (89)Zr-chelating agents for immunoPET applications. The in vitro and in vivo inertness of these new ligands, Orn3-hx (hexadentate) and Orn-4hx derivatives (octadentate), was compared to the gold standard hexadentate, hydroxamate-containing chelator for (89)Zr desferrioxamine (DFO). Density functional theory was employed to model the geometries of the resulting Zr(IV) complexes and to predict their relative stabilities as follows: Zr(Orn4-hx) > Zr(DFC) > Zr(Orn3-hx)...
July 19, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28653240/immunopet-imaging-of-%C3%AE-v%C3%AE-6-expression-using-an-engineered-anti-%C3%AE-v%C3%AE-6-cys-diabody-site-specifically-radiolabeled-with-cu-64-considerations-for-optimal-imaging-with-antibody-fragments
#3
Jason B White, Lina Y Hu, David L Boucher, Julie L Sutcliffe
PURPOSE: Increased expression of the αvβ6 integrin correlates with advanced tumor grade and poor clinical outcome, identifying αvβ6 as a prognostic indicator and an attractive target for molecular imaging. This work investigated the ability of a disulfide-stabilized [(64)Cu]NOTA-αvβ6 cys-diabody to image αvβ6 expression in vivo using a nu/nu mouse model bearing human melanoma xenografts and positron-emission tomography. PROCEDURES: Small-animal positron emission tomography (PET) imaging, quantitative ROI analysis, and ex vivo biodistribution were conducted to ascertain tumor uptake and organ distribution of the [(64)Cu]NOTA-αvβ6 cys-diabody...
June 26, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28596540/preparation-and-in-vivo-characterization-of-51-mncl2-as-pet-tracer-of-ca-2-channel-mediated-transport
#4
Stephen A Graves, Reinier Hernandez, Hector F Valdovinos, Paul A Ellison, Jonathan W Engle, Todd E Barnhart, Weibo Cai, Robert J Nickles
Manganese has long been employed as a T1-shortening agent in magnetic resonance imaging (MRI) applications, but these techniques are limited by the biotoxicity of bulk-manganese. Positron emission tomography (PET) offers superior contrast sensitivity compared with MRI, and recent preclinical PET studies employing (52g)Mn (t1/2: 5.6 d, β(+): 29%) show promise for a variety of applications including cell tracking, neural tract tracing, immunoPET, and functional β-cell mass quantification. The half-life and confounding gamma emissions of (52g)Mn are prohibitive to clinical translation, but the short-lived (51)Mn (t1/2: 46 min, β(+): 97%) represents a viable alternative...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28487384/noninvasive-interrogation-of-dll3-expression-in-metastatic-small-cell-lung-cancer
#5
Sai Kiran Sharma, Jacob Pourat, Dalya Abdel-Atti, Sean D Carlin, Alessandra Piersigilli, Alexander J Bankovich, Eric E Gardner, Omar Hamdy, Kumiko Isse, Sheila Bheddah, Joseph Sandoval, Kristen M Cunanan, Eric B Johansen, Viola Allaj, Vikram Sisodiya, David Liu, Brian M Zeglis, Charles M Rudin, Scott J Dylla, John T Poirier, Jason S Lewis
The Notch ligand DLL3 has emerged as a novel therapeutic target expressed in small cell lung cancer (SCLC) and high-grade neuroendocrine carcinomas. Rovalpituzumab teserine (Rova-T; SC16LD6.5) is a first-in-class DLL3-targeted antibody-drug conjugate with encouraging initial safety and efficacy profiles in SCLC in the clinic. Here we demonstrate that tumor expression of DLL3, although orders of magnitude lower in surface protein expression than typical oncology targets of immunoPET, can serve as an imaging biomarker for SCLC...
May 9, 2017: Cancer Research
https://www.readbyqxmd.com/read/28455978/n-acetylcysteine-breaks-resistance-to-trastuzumab-caused-by-muc4-overexpression-in-human-her2-positive-bc-bearing-nude-mice-monitored-by-89zr-trastuzumab-and-18f-fdg-pet-imaging
#6
Zéna Wimana, Geraldine Gebhart, Thomas Guiot, Bruno Vanderlinden, Denis Larsimont, Gilles Doumont, Gaetan Van Simaeys, Serge Goldman, Patrick Flamen, Ghanem Ghanem
Trastuzumab remains an important drug in the management of human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer (BC). Several studies reported resistance mechanisms to trastuzumab, including impaired HER2-accessibility caused by mucin 4 (MUC4). Previously, we demonstrated an increase of Zirconium-89-radiolabeled-trastuzumab (89Zr-Trastuzumab) accumulation when MUC4-overexpressing BC-cells were challenged with the mucolytic drug N-Acetylcysteine (NAC). Hereby, using the same approach we investigated whether tumor exposure to NAC would also enhance trastuzumab-efficacy...
April 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28443358/cerebral-rituximab-uptake-in-multiple-sclerosis-a-89-zr-immunopet-pilot-study
#7
Marloes Hj Hagens, Joep Killestein, Maqsood M Yaqub, Guus Ams van Dongen, Adriaan A Lammertsma, Frederik Barkhof, Bart Nm van Berckel
Previous studies have demonstrated that the chimeric monoclonal antibody rituximab significantly reduces clinical and radiological disease activity in relapsing-remitting multiple sclerosis as early as 4 weeks after the first administration. The exact mechanisms leading to this rapid effect have not yet been clarified. The aim of this positron emission tomography study was to assess central nervous system penetration as a possible explanation, using zirconium-89-labelled rituximab. No evidence was found for cerebral penetration of [(89)Zr]rituximab...
April 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28388076/immunopet-imaging-of-ctla-4-expression-in-mouse-models-of-non-small-cell-lung-cancer
#8
Emily B Ehlerding, Christopher G England, Rebecca L Majewski, Hector F Valdovinos, Dawei Jiang, Glenn Liu, Douglas G McNeel, Robert J Nickles, Weibo Cai
Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is expressed on the surface of activated T cells and some tumor cells, and is the target of the clinically approved monoclonal antibody ipilimumab. In this study, we investigate specific binding of radiolabeled ipilimumab to CTLA-4 expressed by human non-small cell lung cancer cells in vivo using positron emission tomography (PET). Ipilimumab was radiolabeled with (64)Cu (t1/2 = 12.7 h) through the use of the chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to formulate (64)Cu-DOTA-ipilimumab...
May 1, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28292180/immunopet-and-near-infrared-fluorescence-imaging-of-pancreatic-cancer-with-a-dual-labeled-bispecific-antibody-fragment
#9
Haiming Luo, Christopher G England, Shreya Goel, Stephen A Graves, Fanrong Ai, Bai Liu, Charles P Theuer, Hing C Wong, Robert J Nickles, Weibo Cai
Dual-targeted imaging agents have shown improved targeting efficiencies in comparison to single-targeted entities. The purpose of this study was to quantitatively assess the tumor accumulation of a dual-labeled heterobifunctional imaging agent, targeting two overexpressed biomarkers in pancreatic cancer, using positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging modalities. A bispecific immunoconjugate (heterodimer) of CD105 and tissue factor (TF) Fab' antibody fragments was developed using click chemistry...
May 1, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28265738/radiolabeled-pertuzumab-for-imaging-of-human-epidermal-growth-factor-receptor-2-expression-in-ovarian-cancer
#10
Dawei Jiang, Hyung-Jun Im, Haiyan Sun, Hector F Valdovinos, Christopher G England, Emily B Ehlerding, Robert J Nickles, Dong Soo Lee, Steve Y Cho, Peng Huang, Weibo Cai
PURPOSE: Human epidermal growth factor receptor 2 (HER2) is over-expressed in over 30% of ovarian cancer cases, playing an essential role in tumorigenesis and metastasis. Non-invasive imaging of HER2 is of great interest for physicians as a mean to better detect and monitor the progression of ovarian cancer. In this study, HER2 was assessed as a biomarker for ovarian cancer imaging using (64)Cu-labeled pertuzumab for immunoPET imaging. METHODS: HER2 expression and binding were examined in three ovarian cancer cell lines (SKOV3, OVCAR3, Caov3) using in vitro techniques, including western blot and saturation binding assays...
August 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28247187/development-of-novel-immunopet-tracers-to-image-human-pd-1-checkpoint-expression-on-tumor-infiltrating-lymphocytes-in-a-humanized-mouse-model
#11
Arutselvan Natarajan, Aaron T Mayer, Robert E Reeves, Claude M Nagamine, Sanjiv Sam Gambhir
PURPOSE: It is well known that cancers exploit immune checkpoints (programmed death 1 receptor (PD-1) and its ligand (PD-L1)) to evade anti-tumor immune responses. Although immune checkpoint (IC) blockade is a promising approach, not all patients respond. Hence, imaging of tumor-infiltrating lymphocytes (TILs) is of high specific interest, as they are known to express PD-1 during activation and subsequent exhaustion in the tumor microenvironment and are thought to be potentially predictive of therapeutic responses to IC blockade...
February 28, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/27980047/practical-immuno-pet-radiotracer-design-considerations-for-human-immune-checkpoint-imaging
#12
Aaron T Mayer, Arutselvan Natarajan, Sydney R Gordon, Roy L Maute, Melissa N McCracken, Aaron M Ring, Irving L Weissman, Sanjiv S Gambhir
Immune checkpoint blockade has emerged as a promising cancer treatment paradigm. Unfortunately, there are still a large number of patients and malignancies that do not respond to therapy. A major barrier to validating biomarkers for the prediction and monitoring of responders to clinical checkpoint blockade has been the lack of imaging tools to accurately assess dynamic immune checkpoint expression. Here, we sought to optimize noninvasive immuno-PET imaging of human programmed death-ligand 1 (PD-L1) expression, in a preclinical model, using a small high-affinity engineered protein scaffold (HAC-PD1)...
April 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27966069/immunopet-imaging-of-murine-cd4-t-cells-using-anti-cd4-cys-diabody-effects-of-protein-dose-on-t-cell-function-and-imaging
#13
Amanda C Freise, Kirstin A Zettlitz, Felix B Salazar, Xiang Lu, Richard Tavaré, Anna M Wu
PURPOSE: Molecular imaging of CD4(+) T cells throughout the body has implications for monitoring autoimmune disease and immunotherapy of cancer. Given the key role of these cells in regulating immunity, it is important to develop a biologically inert probe. GK1.5 cys-diabody (cDb), a previously developed anti-mouse CD4 antibody fragment, was tested at different doses to assess its effects on positron emission tomography (PET) imaging and CD4(+) T cell viability, proliferation, CD4 expression, and function...
August 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/27844106/lymphoma-current-status-of-clinical-and-preclinical-imaging-with-radiolabeled-antibodies
#14
REVIEW
Christopher G England, Lixin Rui, Weibo Cai
Lymphoma is a complex disease that arises from cells of the immune system with an intricate pathology. While lymphoma may be classified as Hodgkin or non-Hodgkin, each type of tumor is genetically and phenotypically different and highly invasive tissue biopsies are the only method to investigate these differences. Noninvasive imaging strategies, such as immunoPET, can provide a vital insight into disease staging, monitoring treatment response in patients, and dose planning in radioimmunotherapy. ImmunoPET imaging with radiolabeled antibody-based tracers may also assist physicians in optimizing treatment strategies and enhancing patient stratification...
March 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27760836/preclinical-efficacy-of-an-antibody-drug-conjugate-targeting-mesothelin-correlates-with-quantitative-89zr-immunopet
#15
Anton G T Terwisscha van Scheltinga, Annie Ogasawara, Glenn Pacheco, Alexander N Vanderbilt, Jeff N Tinianow, Nidhi Gupta, Dongwei Li, Ron Firestein, Jan Marik, Suzie J Scales, Simon-Peter Williams
Antibody-drug conjugates (ADC) use monoclonal antibodies (mAb) as vehicles to deliver potent cytotoxic drugs selectively to tumor cells expressing the target. Molecular imaging with zirconium-89 ((89)Zr)-labeled mAbs recapitulates similar targeting biology and might help predict the efficacy of these ADCs. An anti-mesothelin antibody (AMA, MMOT0530A) was used to make comparisons between its efficacy as an ADC and its tumor uptake as measured by (89)Zr immunoPET imaging. Mesothelin-targeted tumor growth inhibition by monomethyl auristatin E (MMAE), ADC AMA-MMAE (DMOT4039A), was measured in mice bearing xenografts of ovarian cancer OVCAR-3×2...
January 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27570560/cd146-targeted-immunopet-and-nirf-imaging-of-hepatocellular-carcinoma-with-a-dual-labeled-monoclonal-antibody
#16
Reinier Hernandez, Haiyan Sun, Christopher G England, Hector F Valdovinos, Emily B Ehlerding, Todd E Barnhart, Yunan Yang, Weibo Cai
Overexpression of CD146 has been correlated with aggressiveness, recurrence rate, and poor overall survival in hepatocellular carcinoma (HCC) patients. In this study, we set out to develop a CD146-targeting probe for high-contrast noninvasive in vivo positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging of HCCs. YY146, an anti-CD146 monoclonal antibody, was employed as a targeting molecule to which we conjugated the zwitterionic near-infrared fluorescence (NIRF) dye ZW800-1 and the chelator deferoxamine (Df)...
2016: Theranostics
https://www.readbyqxmd.com/read/27539021/immunopet-to-help-stratify-patients-for-targeted-therapies-and-to-improve-drug-development
#17
EDITORIAL
Françoise Kraeber-Bodere, Clément Bailly, Michel Chérel, Jean-François Chatal
No abstract text is available yet for this article.
November 2016: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27462980/targeting-mt1-mmp-as-an-immunopet-based-strategy-for-imaging-gliomas
#18
A G de Lucas, A J Schuhmacher, M Oteo, E Romero, J A Cámara, A de Martino, A G Arroyo, M Á Morcillo, M Squatrito, J L Martinez-Torrecuadrada, F Mulero
BACKGROUND: A critical challenge in the management of Glioblastoma Multiforme (GBM) tumors is the accurate diagnosis and assessment of tumor progression in a noninvasive manner. We have identified Membrane-type 1 matrix metalloproteinase (MT1-MMP) as an attractive biomarker for GBM imaging since this protein is actively involved in tumor growth and progression, correlates with tumor grade and is closely associated with poor prognosis in GBM patients. Here, we report the development of an immunoPET tracer for effective detection of MT1-MMP in GBM models...
2016: PloS One
https://www.readbyqxmd.com/read/27446497/high-resolution-pet-imaging-with-therapeutic-antibody-based-pd-1-pd-l1-checkpoint-tracers
#19
Michael Hettich, Friederike Braun, Mark D Bartholomä, Reinhold Schirmbeck, Gabriele Niedermann
Checkpoint-blocking antibodies like those targeting the PD-1/PD-L1 pathway have revolutionized oncology. We developed radiotracers based on therapeutic checkpoint-blocking antibodies permitting sensitive and high-resolution PET imaging of both PD-1 and PD-L1 in immunocompetent mice. ImmunoPET of naive mice revealed similar overall expression patterns for PD-1 and PD-L1 in secondary lymphoid organs (spleen and lymph nodes). Interestingly, PD-L1 was also detected in brown adipose tissue (BAT), confirming the notion that BAT is immunologically relevant...
2016: Theranostics
https://www.readbyqxmd.com/read/27342417/immunopet-for-assessing-the-differential-uptake-of-a-cd146-specific-monoclonal-antibody-in-lung-cancer
#20
Haiyan Sun, Christopher G England, Reinier Hernandez, Stephen A Graves, Rebecca L Majewski, Anyanee Kamkaew, Dawei Jiang, Todd E Barnhart, Yunan Yang, Weibo Cai
PURPOSE: Overexpression of CD146 in solid tumors has been linked to disease progression, invasion, and metastasis. We describe the generation of a (64)Cu-labeled CD146-specific antibody and its use for quantitative immunoPET imaging of CD146 expression in six lung cancer models. METHODS: The anti-CD146 antibody (YY146) was conjugated to 1,4,7-triazacyclononane-triacetic acid (NOTA) and radiolabeled with (64)Cu. CD146 expression was evaluated in six human lung cancer cell lines (A549, NCI-H358, NCI-H522, HCC4006, H23, and NCI-H460) by flow cytometry and quantitative western blot studies...
November 2016: European Journal of Nuclear Medicine and Molecular Imaging
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