Imaging for Response Assessment in Cancer Clinical Trials

Sorace, Anna G.; Elkassem, Asser Abou; Galgano, Samuel J.; Lapi, Suzanne E.; Larimer, Benjamin M.; Partridge, Savannah C.; Quarles, C. Chad; Reeves, Kirsten M.; Napier, Tiara; Song, Patrick N.; Yankeelov, Thomas E.; Woodard, Stefanie; Smith, Andrew D.

doi:10.1053/j.semnuclmed.2020.05.001

Cited by 25 publications

(20 citation statements)

References 128 publications

(160 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As the agreement among different hypoxia-related tracers for PET imaging, or agreement with regional [ 18 F]FDG uptake in NSCLC is modest (220)(221)(222)(223)(224), it remains critical to obtain tissue validation or solid clinical endpoints (225) when incorporating hypoxia tracers in NSCLC studies. However, the most extensively tested hypoxia-related imaging tracer for response prediction in the clinical setting is [ 18 F]FMISO.…”

Section: Hypoxia Imaging To Monitor Response To Immune Checkpoint Inhibitionmentioning

confidence: 99%

Imaging the Rewired Metabolism in Lung Cancer in Relation to Immune Therapy

et al. 2022

View full text Add to dashboard Cite

Metabolic reprogramming is recognized as one of the hallmarks of cancer. Alterations in the micro-environmental metabolic characteristics are recognized as important tools for cancer cells to interact with the resident and infiltrating T-cells within this tumor microenvironment. Cancer-induced metabolic changes in the micro-environment also affect treatment outcomes. In particular, immune therapy efficacy might be blunted because of somatic mutation-driven metabolic determinants of lung cancer such as acidity and oxygenation status. Based on these observations, new onco-immunological treatment strategies increasingly include drugs that interfere with metabolic pathways that consequently affect the composition of the lung cancer tumor microenvironment (TME). Positron emission tomography (PET) imaging has developed a wide array of tracers targeting metabolic pathways, originally intended to improve cancer detection and staging. Paralleling the developments in understanding metabolic reprogramming in cancer cells, as well as its effects on stromal, immune, and endothelial cells, a wave of studies with additional imaging tracers has been published. These tracers are yet underexploited in the perspective of immune therapy. In this review, we provide an overview of currently available PET tracers for clinical studies and discuss their potential roles in the development of effective immune therapeutic strategies, with a focus on lung cancer. We report on ongoing efforts that include PET/CT to understand the outcomes of interactions between cancer cells and T-cells in the lung cancer microenvironment, and we identify areas of research which are yet unchartered. Thereby, we aim to provide a starting point for molecular imaging driven studies to understand and exploit metabolic features of lung cancer to optimize immune therapy.

show abstract

Section: Hypoxia Imaging To Monitor Response To Immune Checkpoint Inhibitionmentioning

confidence: 99%

Imaging the Rewired Metabolism in Lung Cancer in Relation to Immune Therapy

et al. 2022

View full text Add to dashboard Cite

show abstract

“…[ 18 F]-FMISO is a well-known hypoxia marker that has been shown to be useful as a prognostic marker, in glioma but also in other tumours [ 71 , 72 ], with an uptake mechanism proven to be hypoxia-dependent and glutathione conjugation [ 73 ]. Due to suboptimal pharmacokinetics, 18 F-FMISO is not ideal for imaging hypoxia however, and alternative tracers are being investigated.…”

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

View full text Add to dashboard Cite

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.

show abstract

“…Molecular imaging techniques such as positron emission tomography (PET) provide the ability to noninvasively visualize and quantify biomarkers associated with the interactions that occur between tumor cells and the immune system. Numerous PET agents that target either immune cell lineage markers or functional proteins associated with immune function have been explored [11]. These approaches provide non-invasive quantification of the presence and phenotype of specific immune cell populations but lack the ability to directly measure immunosuppressive physical characteristics of the tumor.…”

Section: Introductionmentioning

confidence: 99%

“…The PET imaging agent, fluoromisonidazole ( 18 F-FMISO), quantitatively measures hypoxia levels intratumorally, as it is retained by irreversible binding to the thiol-rich metabolic proteins at rates that are inversely proportional to oxygen concentration [12]. 18 F-FMISO has been extensively used in clinical trials in glioblastoma, but its widespread incorporation has been hindered by a lack of sensitivity to measure less hypoxic regions of tumors [11]. However, this characteristic may be beneficial for immunotherapy, where severe hypoxia is more likely to be associated with a suppressive immune microenvironment.…”

Section: Introductionmentioning

confidence: 99%

18F-FMISO PET Imaging Identifies Hypoxia and Immunosuppressive Tumor Microenvironments and Guides Targeted Evofosfamide Therapy in Tumors Refractory to PD-1 and CTLA-4 Inhibition

Reeves

Song

Angermeier

et al. 2021

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

Hypoxia is a well-known component of many tumors and acts in an immunosuppressive manner through multiple distinct pathways. 18 F-FMISO PET imaging has been demonstrated to accurately quantify hypoxia in a clinical setting, although it has not been investigated for immunotherapy. Our work demonstrates that effective immunotherapy prevents tumor hypoxia and that uptake of 18 F-FMISO was predictive of subsequent changes in anatomical tumor size. We further demonstrate that PET imaging of hypoxia is correlated with phenotypic characteristics of inflammation through transcriptomics, immune cell spatial correlation, and direct measurement of secreted inflammatory proteins. The upregulation of damage associated molecular pattern signaling in responding tumors warranted investigation of the addition of the hypoxia targeted pro-drug to non-responding tumors in order to enhance checkpoint blockade efficacy. The addition of evofosfamide improved tumor oxygenation and response, providing rationale for immediate clinical investigation of both 18 F-FMISO PET imaging and combination evofosfamide therapy for improved cancer immunotherapy.Research.

show abstract

Imaging for Response Assessment in Cancer Clinical Trials

Cited by 25 publications

References 128 publications

Imaging the Rewired Metabolism in Lung Cancer in Relation to Immune Therapy

Imaging the Rewired Metabolism in Lung Cancer in Relation to Immune Therapy

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

18F-FMISO PET Imaging Identifies Hypoxia and Immunosuppressive Tumor Microenvironments and Guides Targeted Evofosfamide Therapy in Tumors Refractory to PD-1 and CTLA-4 Inhibition

Contact Info

Product

Resources

About