Specific biomarkers of receptors, pathways of inhibition and targeted therapies: clinical applications

Waerzeggers, Yannic; Ullrich, Roland T.; Monfared, Parisa; Viel, Thomas; Weckesser, Matthias; Stummer, Walter; Schober, O.; Winkeler, Alexandra

doi:10.1259/bjr/76389842

Cited by 4 publications

(2 citation statements)

References 127 publications

(147 reference statements)

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“…Downstream signaling components, such as hypoxia inducible factor-1 (HIF-1), have also been targeted with radiotracers and imaged using PET [23]. Radiotracers that target signalling components such as these may have clinical application in the stratification of patients and the assessment of the treatment response [24,25].…”

Section: The Pre-clinical and Clinical Value Of Pet Or Spect Imagingmentioning

confidence: 99%

PET and SPECT Imaging for the Acceleration of Anti-Cancer Drug Development

Hillyar¹,

Knight²,

Vallis³

et al. 2015

CDT

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Lead-compound optimization is an iterative process in the cancer drug development pipeline, in which small molecule inhibitors or biological compounds that are selected for their ability to bind specific targets are synthesised, tested and optimised. This process can be accelerated significantly using molecular imaging with nuclear medicine techniques, which aim to monitor the biodistribution and pharmacokinetics of radiolabelled versions of compounds. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) can be used to quantify fourdimensional (temporal and spatial) clinically relevant information, to demonstrate tumor uptake of, and monitor the response to treatment with lead-compounds. This review discusses the pre-clinical and clinical value of the information provided by nuclear medicine imaging compared to the histological analysis of biopsied tissue samples. Also, the role of nuclear medicine imaging is discussed with regard to the assessment of the treatment response, radiotracer biodistribution, tumor accumulation, toxicity, and pharmacokinetic parameters, with mention of microdosing studies, pre-targeting strategies, and pharmacokinetic modelling.

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Section: The Pre-clinical and Clinical Value Of Pet Or Spect Imagingmentioning

confidence: 99%

PET and SPECT Imaging for the Acceleration of Anti-Cancer Drug Development

Hillyar¹,

Knight²,

Vallis³

et al. 2015

CDT

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show abstract

“…In addition to the Omics techniques that are becoming an integral part of standard tests for patient care, molecular imaging technologies are also used to provide in vivo evaluation of diagnosis, disease progression, and targeted therapy . The value of molecular imaging technologies for guiding therapeutic intervention is currently under evaluation in numerous clinical trials for a broad range of diseases . In other applications, therapeutic ligands are made visible by a variety of imaging technologies in order to verify and quantify therapeutic interventions.…”

Section: Introductionmentioning

confidence: 99%

Feasibility study of a point‐of‐care positron emission tomography system with interactive imaging capability

Jiang

Komarov

et al. 2019

Medical Physics

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Purpose: We investigated the feasibility of a novel positron emission tomography (PET) system that provides near real-time feedback to an operator who can interactively scan a patient to optimize image quality. The system should be compact and mobile to support point-of-care (POC) molecular imaging applications. In this study, we present the key technologies required and discuss the potential benefits of such new capability. Methods: The core of this novel PET technology includes trackable PET detectors and a fully threedimensional, fast image reconstruction engine implemented on multiple graphics processing units (GPUs) to support dynamically changing geometry by calculating the system matrix on-the-fly using a tube-of-response approach. With near real-time image reconstruction capability, a POC-PET system may comprise a maneuverable front PET detector and a second detector panel which can be stationary or moved synchronously with the front detector such that both panels face the region-of-interest (ROI) with the detector trajectory contoured around a patient's body. We built a proof-of-concept prototype using two planar detectors each consisting of a photomultiplier tube (PMT) optically coupled to an array of 48 9 48 lutetium-yttrium oxyorthosilicate (LYSO) crystals (1.0 9 1.0 9 10.0 mm 3 each). Only 38 9 38 crystals in each arrays can be clearly re-solved and used for coincidence detection. One detector was mounted to a robotic arm which can position it at arbitrary locations, and the other detector was mounted on a rotational stage. A cylindrical phantom (102 mm in diameter, 150 mm long) with nine spherical lesions (8:1 tumor-to-background activity concentration ratio) was imaged from 27 sampling angles. List-mode events were reconstructed to form images without or with time-of-flight (TOF) information. We conducted two Monte Carlo simulations using two POC-PET systems. The first one uses the same phantom and detector setup as our experiment, with the detector coincidence re-solving time (CRT) ranging from 100 to 700 ps full-width-at-half-maximum (FWHM). The second study simulates a body-size phantom (316 9 228 9 160 mm 3 ) imaged by a larger POC-PET system that has 4 9 6 modules (32 9 32 LYSO crystals/module, four in axial and six in transaxial directions) in the front panel and 3 9 8 modules (16 9 16 LYSO crystals/module, three in axial and eight in transaxial directions) in the back panel. We also evaluated an interactive scanning strategy by progressively increasing the number of data sets used for image reconstruction. The updated images were analyzed based on the number of data sets and the detector CRT. Results: The proof-of-concept prototype re-solves most of the spherical lesions despite a limited number of coincidence events and incomplete sampling. TOF information reduces artifacts in the reconstructed images. Systems with better timing resolution exhibit improved image quality and reduced artifacts. We observed a reconstruction speed of 0.96 9 10 6 events/s/iteration for 600 9 600 9 224 voxel rect...

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RNAi-mediated SYT14 knockdown inhibits the growth of human glioma cell line U87MG

Sheng

Jiang

et al. 2018

Brain Research Bulletin

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Specific biomarkers of receptors, pathways of inhibition and targeted therapies: clinical applications

Cited by 4 publications

References 127 publications

PET and SPECT Imaging for the Acceleration of Anti-Cancer Drug Development

PET and SPECT Imaging for the Acceleration of Anti-Cancer Drug Development

Feasibility study of a point‐of‐care positron emission tomography system with interactive imaging capability

RNAi-mediated SYT14 knockdown inhibits the growth of human glioma cell line U87MG

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