P2-09-01: First-in-Human Whole-Body HER2−Receptor Mapping Using Affibody Molecular Imaging.

2011 ◽  
Author(s):  
D Sandberg ◽  
A Wennborg ◽  
J Feldwisch ◽  
J Sörensen ◽  
U Garske ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Whole Body ◽  
Her2 Receptor ◽  
Receptor Mapping

scholarly journals Has molecular imaging delivered to drug development?

2017 ◽  
Vol 375 (2107) ◽  
pp. 20170112 ◽  
Author(s):  
Philip S. Murphy ◽  
Neel Patel ◽  
Timothy J. McCarthy
Keyword(s):  
Molecular Imaging ◽  
Drug Development ◽  
Clinical Studies ◽  
Pharmaceutical Research ◽  
Whole Body ◽  
Drug Candidate ◽  
Clinical Drug Development ◽  
Target Binding ◽  
The Brain ◽  
Clinical Drug

Pharmaceutical research and development requires a systematic interrogation of a candidate molecule through clinical studies. To ensure resources are spent on only the most promising molecules, early clinical studies must understand fundamental attributes of the drug candidate, including exposure at the target site, target binding and pharmacological response in disease. Molecular imaging has the potential to quantitatively characterize these properties in small, efficient clinical studies. Specific benefits of molecular imaging in this setting (compared to blood and tissue sampling) include non-invasiveness and the ability to survey the whole body temporally. These methods have been adopted primarily for neuroscience drug development, catalysed by the inability to access the brain compartment by other means. If we believe molecular imaging is a technology platform able to underpin clinical drug development, why is it not adopted further to enable earlier decisions? This article considers current drug development needs, progress towards integration of molecular imaging into studies, current impediments and proposed models to broaden use and increase impact. This article is part of the themed issue ‘Challenges for chemistry in molecular imaging’.

scholarly journals Personalized management of differentiated thyroid cancer in real life – practical guidance from a multidisciplinary panel of experts

Endocrine ◽  
2020 ◽  
Vol 70 (2) ◽  
pp. 280-291
Author(s):  
Alfredo Campennì ◽  
Daniele Barbaro ◽  
Marco Guzzo ◽  
Francesca Capoccetti ◽  
Luca Giovanella
Keyword(s):  
Nuclear Medicine ◽  
Thyroid Cancer ◽  
Clinical Practice ◽  
Molecular Imaging ◽  
Routine Clinical Practice ◽  
Whole Body ◽  
Neck Ultrasound ◽  
Long Term Follow Up

Abstract Purpose The standard of care for differentiated thyroid carcinoma (DTC) includes surgery, risk-adapted postoperative radioiodine therapy (RaIT), individualized thyroid hormone therapy, and follow-up for detection of patients with persistent or recurrent disease. In 2019, the nine Martinique Principles for managing thyroid cancer were developed by the American Thyroid Association, European Association of Nuclear Medicine, Society of Nuclear Medicine and Molecular Imaging, and European Thyroid Association. In this review, we present our clinical practice recommendations with regard to implementing these principles in the diagnosis, treatment, and long-term follow-up of patients with DTC. Methods A multidisciplinary panel of five thyroid cancer experts addressed the implementation of the Martinique Principles in routine clinical practice based on clinical experience and evidence from the literature. Results We provide a suggested approach for the assessment and diagnosis of DTC in routine clinical practice, including the use of neck ultrasound, measurement of serum thyroid-stimulating hormone and calcitonin, fine-needle aspiration, cytology, and molecular imaging. Recommendations for the use of surgery (lobectomy vs. total thyroidectomy) and postoperative RaIT are also provided. Long-term follow-up with neck ultrasound and measurement of serum anti-thyroglobulin antibody and basal/stimulated thyroglobulin is standard, with 123/131I radioiodine diagnostic whole-body scans and 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography suggested in selected patients. Management of metastatic DTC should involve a multidisciplinary team. Conclusions In routine clinical practice, the Martinique Principles should be implemented in order to optimize clinical management/outcomes of patients with DTC.

scholarly journals A whole-body Fast Field-Cycling scanner for clinical molecular imaging studies

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Lionel M. Broche ◽  
P. James Ross ◽  
Gareth R. Davies ◽  
Mary-Joan MacLeod ◽  
David J. Lurie
Keyword(s):  
Molecular Imaging ◽  
Whole Body ◽  
Imaging Studies ◽  
Field Cycling ◽  
Fast Field

Design of Peptide Imaging Agents for Whole-body and Intraoperative Molecular Imaging

2012 ◽  
Vol 19 (20) ◽  
pp. 3255-3265 ◽  
Author(s):  
J. A. Moss ◽  
A. L. Vavere ◽  
A. Azhdarinia
Keyword(s):  
Molecular Imaging ◽  
Whole Body ◽  
Imaging Agents ◽  
Peptide Imaging

scholarly journals High Performance Molecular Imaging with MALDI Trapped Ion Mobility Time-of-Flight (timsTOF) Mass Spectrometry

2019 ◽  
Author(s):  
Jeffrey Spraggins ◽  
Katerina Djambazova ◽  
Emilio Rivera ◽  
Lukasz Migas ◽  
Elizabeth Neumann ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Molecular Imaging ◽  
Spatial Resolution ◽  
Ion Mobility ◽  
Measurement Errors ◽  
High Performance ◽  
High Spatial Resolution ◽  
Biological Tissues ◽  
Whole Body ◽  
Trapped Ion

Imaging mass spectrometry (IMS) enables the spatially targeted molecular assessment of biological tissues at cellular resolutions. New developments and technologies are essential for uncovering the molecular drivers of native physiological function and disease. Instrumentation must maximize spatial resolution, throughput, sensitivity, and specificity, because tissue imaging experiments consist of thousands to millions of pixels. Here, we report the development and application of a matrix-assisted laser desorption/ionization (MALDI) trapped ion mobility spectrometry imaging platform. This prototype MALDI timsTOF instrument is capable of 10 µm spatial resolutions and 20 pixels/s throughput molecular imaging. The MALDI source utilizes a Bruker SmartBeam 3-D laser system that can generate a square burn pattern of <10 x 10 µm at the sample surface. General image performance was assessed using murine kidney and brain tissues and demonstrate that high spatial resolution imaging data can be generated rapidly with mass measurement errors < 5 ppm and ~40,000 resolving power. Initial TIMS-based imaging experiments were performed on whole body mouse pup tissue demonstrating the separation of closely isobaric [PC(32:0)+Na]<sup>+</sup>and [PC(34:3)+H]<sup>+</sup>(3 mDa mass difference) in the gas-phase. We have shown that the MALDI timsTOF platform can maintain reasonable data acquisition rates (>2 pixels/s) while providing the specificity necessary to differentiate components in complex mixtures of lipid adducts. The combination of high spatial resolution and throughput imaging capabilities with high-performance TIMS separations provides a uniquely tunable platform to address many challenges associated with advanced molecular imaging applications.

scholarly journals Early molecular imaging response assessment based on determination of total viable tumor burden in [68Ga]Ga-PSMA-11 PET/CT independently predicts overall survival in [177Lu]Lu-PSMA-617 radioligand therapy

2021 ◽  
Author(s):  
Florian Rosar ◽  
Felix Wenner ◽  
Fadi Khreish ◽  
Sebastian Dewes ◽  
Gudrun Wagenpfeil ◽  
...  
Keyword(s):  
Overall Survival ◽  
Molecular Imaging ◽  
Multivariable Analysis ◽  
Response Assessment ◽  
Tumor Burden ◽  
Whole Body ◽  
Biochemical Response ◽  
Radioligand Therapy ◽  
Pet Ct ◽  
Imaging Response

Abstract Purpose In patients with metastatic castration-resistant prostate cancer (mCRPC) treated with prostate-specific membrane antigen-targeted radioligand therapy (PSMA-RLT), the predictive value of PSMA PET/CT-derived response is still under investigation. Early molecular imaging response based on total viable tumor burden and its association with overall survival (OS) was explored in this study. Methods Sixty-six mCRPC patients who received [177Lu]Lu-PSMA-617 RLT within a prospective patient registry (REALITY Study, NCT04833517) were analyzed. Patients received a [68Ga]Ga-PSMA-11 PET/CT scan before the first and after the second cycle of PSMA-RLT. Total lesion PSMA (TLP) was determined by semiautomatic whole-body tumor segmentation. Molecular imaging response was assessed by change in TLP and modified PERCIST criteria. Biochemical response was assessed using standard serum PSA and PCWG3 criteria. Both response assessment methods and additional baseline parameters were analyzed regarding their association with OS by univariate and multivariable analysis. Results By molecular imaging, 40/66 (60.6%) patients showed partial remission (PR), 19/66 (28.7%) stable disease (SD), and 7/66 (10.6%) progressive disease (PD). Biochemical response assessment revealed PR in 34/66 (51.5%) patients, SD in 20/66 (30.3%), and PD in 12/66 (18.2%). Response assessments were concordant in 49/66 (74.3%) cases. On univariate analysis, both molecular and biochemical response (p = 0.001 and 0.008, respectively) as well as two baseline characteristics (ALP and ECOG) were each significantly associated with OS. The median OS of patients showing molecular PR was 24.6 versus 10.7 months in the remaining patients (with SD or PD). On multivariable analysis molecular imaging response remained an independent predictor of OS (p = 0.002), eliminating biochemical response as insignificant (p = 0.515). Conclusion The new whole-body molecular imaging–derived biomarker, early change of total lesion PSMA (TLP), independently predicts overall survival in [177Lu]Lu-PSMA-617 RLT in mCRPC, outperforming conventional PSA-based response assessment. TLP might be considered a more distinguished and advanced biomarker for monitoring PSMA-RLT over commonly used serum PSA.

scholarly journals Identify. Quantify. Predict. Why Immunologists Should Widely Use Molecular Imaging for Coronavirus Disease 2019

2021 ◽  
Vol 12 ◽  
Author(s):  
Freimut D. Juengling ◽  
Antonio Maldonado ◽  
Frank Wuest ◽  
Thomas H. Schindler
Keyword(s):  
Molecular Imaging ◽  
Current Knowledge ◽  
Imaging Modality ◽  
Acute Infection ◽  
Molecular Probes ◽  
Whole Body ◽  
Prognostic Indicators ◽  
Imaging Biomarkers ◽  
Body Scale

Molecular imaging using PET/CT or PET/MRI has evolved from an experimental imaging modality at its inception in 1972 to an integral component of diagnostic procedures in oncology, and, to lesser extent, in cardiology and neurology, by successfully offering in-vivo imaging and quantitation of key pathophysiological targets or molecular signatures, such as glucose metabolism in cancerous disease. Apart from metabolism probes, novel radiolabeled peptide and antibody PET tracers, including radiolabeled monoclonal antibodies (mAbs) have entered the clinical arena, providing the in-vivo capability to collect target-specific quantitative in-vivo data on cellular and molecular pathomechanisms on a whole-body scale, and eventually, extract imaging biomarkers possibly serving as prognostic indicators. The success of molecular imaging in mapping disease severity on a whole-body scale, and directing targeted therapies in oncology possibly could translate to the management of Coronavirus Disease 2019 (COVID-19), by identifying, localizing, and quantifying involvement of different immune mediated responses to the infection with SARS-COV2 during the course of acute infection and possible, chronic courses with long-term effects on specific organs. The authors summarize current knowledge for medical imaging in COVID-19 in general with a focus on molecular imaging technology and provide a perspective for immunologists interested in molecular imaging research using validated and immediately available molecular probes, as well as possible future targets, highlighting key targets for tailored treatment approaches as brought up by key opinion leaders.

High Performance Molecular Imaging with MALDI Trapped Ion Mobility Time-of-Flight (timsTOF) Mass Spectrometry

2019 ◽  
Author(s):  
Jeffrey Spraggins ◽  
Katerina Djambazova ◽  
Emilio Rivera ◽  
Lukasz Migas ◽  
Elizabeth Neumann ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Molecular Imaging ◽  
Spatial Resolution ◽  
Ion Mobility ◽  
Measurement Errors ◽  
High Performance ◽  
High Spatial Resolution ◽  
Biological Tissues ◽  
Whole Body ◽  
Trapped Ion

Imaging mass spectrometry (IMS) enables the spatially targeted molecular assessment of biological tissues at cellular resolutions. New developments and technologies are essential for uncovering the molecular drivers of native physiological function and disease. Instrumentation must maximize spatial resolution, throughput, sensitivity, and specificity, because tissue imaging experiments consist of thousands to millions of pixels. Here, we report the development and application of a matrix-assisted laser desorption/ionization (MALDI) trapped ion mobility spectrometry imaging platform. This prototype MALDI timsTOF instrument is capable of 10 µm spatial resolutions and 20 pixels/s throughput molecular imaging. The MALDI source utilizes a Bruker SmartBeam 3-D laser system that can generate a square burn pattern of <10 x 10 µm at the sample surface. General image performance was assessed using murine kidney and brain tissues and demonstrate that high spatial resolution imaging data can be generated rapidly with mass measurement errors < 5 ppm and ~40,000 resolving power. Initial TIMS-based imaging experiments were performed on whole body mouse pup tissue demonstrating the separation of closely isobaric [PC(32:0)+Na]<sup>+</sup>and [PC(34:3)+H]<sup>+</sup>(3 mDa mass difference) in the gas-phase. We have shown that the MALDI timsTOF platform can maintain reasonable data acquisition rates (>2 pixels/s) while providing the specificity necessary to differentiate components in complex mixtures of lipid adducts. The combination of high spatial resolution and throughput imaging capabilities with high-performance TIMS separations provides a uniquely tunable platform to address many challenges associated with advanced molecular imaging applications.

Abstract 14935: Targeted Optical Molecular Imaging of Atheroma Calcification Using Novel Aldendronate-based Probe

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Dong Oh Kang ◽  
Yong Geun Lim ◽  
Joon Woo Song ◽  
Ye Hee Park ◽  
Hyun Jung Kim ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
High Resolution ◽  
Murine Model ◽  
Calcium Binding ◽  
Laser Scanning ◽  
Near Infrared ◽  
Imaging System ◽  
Whole Body ◽  
Imaging Results

Background/Objectives: Vascular spotty calcification is an actively regulated biological process resulting in plaque vulnerability. We investigated the feasibility of a novel alendronate-based near-infrared fluorescence (NIRF)-emitting probe to specifically target atherosclerotic calcification in a murine model in vivo using our customized high-resolution multichannel intravital molecular imaging system (IVFM). Methods/Results: We have fabricated a calcium-binding NIRF probe by chemically coupling alendronate, a specific targeting ligand, and NIRF-emitting Cy5.5 to the ends of azide-PEG-NHS ester (Al-Cy5.5). Prepared Al-Cy5.5 has high affinity for calcium phosphate-containing bone minerals. In vitro, Al-Cy5.5 specifically binds to RANKL-induced osteogenic-macrophages as compared to macrophages (p<0.01). On whole body fluorescence imaging to assess time-dependent excretion, NIRF signals remained visible up to 48 hrs. Then, in mice with calcified plaque induced by a combination diet of high-cholesterol and warfarin, Al-Cy5.5 (2.5 mg/kg) was intravenously injected. 48 hrs after administration, murine calcified atheroma was assessed using a customized high-resolution multichannel IVFM, which demonstrated highly enhanced NIRF signals in vivo in the calcified areas of murine carotid plaques (p<0.01, Figure). Ex vivo laser scanning fluorescence microscopic and immune-histological findings from the corresponding sister sections well corroborated the in vivo imaging results, which demonstrated the co-localization of NIRF signals with plaque calcifications (von-Kossa stain). Conclusions: Our novel calcification targeted probe, Al-Cy5.5, was able to selectively target atheroma calcification in vivo in a murine model as assessed by optical IVFM. This novel targetable strategy is expected to provide a promising theranostic basis for calcified high-risk plaques by integration with multimodal customized catheter imaging system.

C Development of Whole Body and Intravascular Near-infrared Optical Molecular Imaging of Markers of Plaque Vulnerablity in Atherosclerosis

Heart ◽  
2014 ◽  
Vol 100 (Suppl 3) ◽  
pp. A128.1-A128
Author(s):  
Ramzi Y Khamis ◽  
Kevin J Woollard ◽  
Gareth D Hyde ◽  
Joseph J Boyle ◽  
Colin Bicknell ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Near Infrared ◽  
Whole Body ◽  
Optical Molecular Imaging
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