Hypoxia PET Imaging with [18F]-HX4—A Promising Next-Generation Tracer

Sanduleanu, Sebastian; Wiel, Alexander M.A. van der; Lieverse, Ritsaert; Marcus, Damiënne; Ibrahim, Abdalla; Primakov, Sergey; Wu, Guangyao; Theys, Jan; Yaromina, Ala; Dubois, Ludwig; Lambin, Philippe

doi:10.3390/cancers12051322

Cited by 41 publications

(26 citation statements)

References 76 publications

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“…In terms of accuracy, PET radiotracers are promising as non-invasive procedures. The [ 18 F]-HX4 tracer seems the most promising in the hypoxia field but the signal-to-noise ratio requires improvement [ 175 ]. Larger cohorts are needed to establish clinical relevance, by confronting various PET-acquired parameters with pathologically-matched hypoxia features and association with prognostics.…”

Section: Available Tools To Detect Hypoxia In Clinical Practicementioning

confidence: 99%

Hypoxia in Lung Cancer Management: A Translational Approach

Ancel

Perotin

Dewolf

et al. 2021

Cancers

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Lung cancer represents the first cause of death by cancer worldwide and remains a challenging public health issue. Hypoxia, as a relevant biomarker, has raised high expectations for clinical practice. Here, we review clinical and pathological features related to hypoxic lung tumours. Secondly, we expound on the main current techniques to evaluate hypoxic status in NSCLC focusing on positive emission tomography. We present existing alternative experimental approaches such as the examination of circulating markers and highlight the interest in non-invasive markers. Finally, we evaluate the relevance of investigating hypoxia in lung cancer management as a companion biomarker at various lung cancer stages. Hypoxia could support the identification of patients with higher risks of NSCLC. Moreover, the presence of hypoxia in treated tumours could help clinicians predict a worse prognosis for patients with resected NSCLC and may help identify patients who would benefit potentially from adjuvant therapies. Globally, the large quantity of translational data incites experimental and clinical studies to implement the characterisation of hypoxia in clinical NSCLC management.

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Section: Available Tools To Detect Hypoxia In Clinical Practicementioning

confidence: 99%

Hypoxia in Lung Cancer Management: A Translational Approach

Ancel

Perotin

Dewolf

et al. 2021

Cancers

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“…[ 18 F]-Flortanidazole ([ 18 F]-HX4) was developed and validated both preclinically and clinically as a third-generation nitroimidazole-based tracer, with an even faster clearance and improved distribution [ 80 ]. Although we could not find any direct comparison of [ 18 F]-HX4 and angiogenesis markers, its improved biodistribution and tumour visualization as demonstrated in several clinical trials make this a strong candidate for future (attempts at) imaging of angiogenesis in hypoxia-rich environments [ 81 , 82 , 83 ].…”

Section: Indirect Targeting Of Angiogenesismentioning

confidence: 99%

“…Although PSMA is not expressed in non-prostate tumours, nor in healthy vasculature, expression does occur in endothelial cells of tumour-associated neovasculature [ 86 ]. Two excellent reviews of PSMA-based imaging in non-prostate imaging have been recently published [ 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 ], but we would like to briefly present the findings regarding angiogenesis here. The functional role of PSMA in angiogenesis is not clear at this moment, nor is PSMA a requirement for tumour-associated neovascularisation—but PSMA expression is associated to tumours that critically depend on angiogenesis.…”

Section: Indirect Targeting Of Angiogenesismentioning

confidence: 99%

Molecular Imaging of Angiogenesis in Oncology: Current Preclinical and Clinical Status

Florea

Mottaghy

Bauwens

2021

IJMS

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Angiogenesis is an active process, regulating new vessel growth, and is crucial for the survival and growth of tumours next to other complex factors in the tumour microenvironment. We present possible molecular imaging approaches for tumour vascularisation and vitality, focusing on radiopharmaceuticals (tracers). Molecular imaging in general has become an integrated part of cancer therapy, by bringing relevant insights on tumour angiogenic status. After a structured PubMed search, the resulting publication list was screened for oncology related publications in animals and humans, disregarding any cardiovascular findings. The tracers identified can be subdivided into direct targeting of angiogenesis (i.e., vascular endothelial growth factor, laminin, and fibronectin) and indirect targeting (i.e., glucose metabolism, hypoxia, and matrix metallo-proteases, PSMA). Presenting pre-clinical and clinical data of most tracers proposed in the literature, the indirect targeting agents are not 1:1 correlated with angiogenesis factors but do have a strong prognostic power in a clinical setting, while direct targeting agents show most potential and specificity for assessing tumour vascularisation and vitality. Within the direct agents, the combination of multiple targeting tracers into one agent (multimers) seems most promising. This review demonstrates the present clinical applicability of indirect agents, but also the need for more extensive research in the field of direct targeting of angiogenesis in oncology. Although there is currently no direct tracer that can be singled out, the RGD tracer family seems to show the highest potential therefore we expect one of them to enter the clinical routine.

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“…Several factors play roles in the radio- and chemoresistance of solid tumors, including hypoxia, DNA-repair deficiencies, and cellular senescence [ 49 ]. Among these features, hypoxia offers the possibility to be analyzed using advanced imaging techniques such as specific hypoxia positron emission tomography (PET) tracers [ 50 ] and diffusion-weighted MRI [ 31 ]. In NSCLC, the noninvasive detection of hypoxia has been demonstrated for a combination of PET/CT and dynamic contrast-enhanced CT [ 51 ].…”

Section: Ai For Biomarker Discovery From Medical Imaging To Biologymentioning

confidence: 99%

Artificial Intelligence Applications to Improve the Treatment of Locally Advanced Non-Small Cell Lung Cancers

Hope

Verduin

Choudhury

et al. 2021

Cancers

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Locally advanced non-small cell lung cancer patients represent around one third of newly diagnosed lung cancer patients. There remains a large unmet need to find treatment strategies that can improve the survival of these patients while minimizing therapeutical side effects. Increasing the availability of patients’ data (imaging, electronic health records, patients’ reported outcomes, and genomics) will enable the application of AI algorithms to improve therapy selections. In this review, we discuss how artificial intelligence (AI) can be integral to improving clinical decision support systems. To realize this, a roadmap for AI must be defined. We define six milestones involving a broad spectrum of stakeholders, from physicians to patients, that we feel are necessary for an optimal transition of AI into the clinic.

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Hypoxia PET Imaging with [18F]-HX4—A Promising Next-Generation Tracer

Cited by 41 publications

References 76 publications

Hypoxia in Lung Cancer Management: A Translational Approach

Hypoxia in Lung Cancer Management: A Translational Approach

Molecular Imaging of Angiogenesis in Oncology: Current Preclinical and Clinical Status

Artificial Intelligence Applications to Improve the Treatment of Locally Advanced Non-Small Cell Lung Cancers

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