Resolution of Spatial and Temporal Heterogeneity in Bevacizumab-Treated Breast Tumors by Eigenspectra Multispectral Optoacoustic Tomography

Liapis, Evangelos; Klemm, Uwe; Karlas, Angelos; Reber, Josefine; Ntziachristos, Vasilis

doi:10.1158/0008-5472.can-20-1011

Cited by 17 publications

(23 citation statements)

References 55 publications

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“…Liapis et al. ( 36 ) highlight the importance of data collection immediately following the administration of therapeutic agents. Similarly, Hysi et al.…”

Section: Introductionmentioning

confidence: 99%

“…However, this study did not choose to examine pretreatment conditions (i.e., volume or baseline StO 2 ). A recent study by Liapis et al (36) longitudinally examined tumor hemodynamics in two types of breast cancer xenografts focusing particularly on HbT and StO 2 changes with the administration of bevacizumab, a drug that targets circulating VEGF and prevents it from attaching to its cell membrane receptors. They observed a sharp drop in tumor StO 2 and HbT concentration shortly after initiation of treatment that was then restored back to pretreatment levels.…”

Section: Introductionmentioning

confidence: 99%

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3D Ultrasound-Guided Photoacoustic Imaging to Monitor the Effects of Suboptimal Tyrosine Kinase Inhibitor Therapy in Pancreatic Tumors

et al. 2022

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Pancreatic cancer is a disease with an incredibly poor survival rate. As only about 20% of patients are eligible for surgical resection, neoadjuvant treatments that can relieve symptoms and shrink tumors for surgical resection become critical. Many forms of treatments rely on increased vulnerability of cancerous cells, but tumors or regions within the tumors that may be hypoxic could be drug resistant. Particularly for neoadjuvant therapies such as the tyrosine kinase inhibitors utilized to shrink tumors, it is critical to monitor changes in vascular function and hypoxia to predict treatment efficacy. Current clinical imaging modalities used to obtain structural and functional information regarding hypoxia or oxygen saturation (StO2) do not provide sufficient depth penetration or require the use of exogenous contrast agents. Recently, ultrasound-guided photoacoustic imaging (US-PAI) has garnered significant popularity, as it can noninvasively provide multiparametric information on tumor vasculature and function without the need for contrast agents. Here, we built upon existing literature on US-PAI and demonstrate the importance of changes in StO2 values to predict treatment response, particularly tumor growth rate, when the outcomes are suboptimal. Specifically, we image xenograft mouse models of pancreatic adenocarcinoma treated with suboptimal doses of a tyrosine kinase inhibitor cabozantinib. We utilize the US-PAI data to develop a multivariate regression model that demonstrates that a therapy-induced reduction in tumor growth rate can be predicted with 100% positive predictive power and a moderate (58.33%) negative predictive power when a combination of pretreatment tumor volume and changes in StO2 values pretreatment and immediately posttreatment was employed. Overall, our study indicates that US-PAI has the potential to provide label-free surrogate imaging biomarkers that can predict tumor growth rate in suboptimal therapy.

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“…Liapis et al. ( 36 ) highlight the importance of data collection immediately following the administration of therapeutic agents. Similarly, Hysi et al.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

3D Ultrasound-Guided Photoacoustic Imaging to Monitor the Effects of Suboptimal Tyrosine Kinase Inhibitor Therapy in Pancreatic Tumors

et al. 2022

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“…Some preclinical studies revealed tumor shrinkage after anti-VEGF therapy, others suggesting vascular normalization have been related to increased rates of tumor growth [108]. Data from clinical studies in breast cancer and glioblastoma patients treated with bevacizumab are also contradictory, with some studies reporting increased oxygenation in tumors, and others describing aggravation in intratumoral hypoxia [109]. Besides, the induction of hypoxia by anti-angiogenic agents have been proven to increase numbers of breast cancer stem cells [110].…”

Section: Vessel Normalizationmentioning

confidence: 99%

Targeting hypoxia in the tumor microenvironment: a potential strategy to improve cancer immunotherapy

Wang

Zhao

Zhang

et al. 2021

J Exp Clin Cancer Res

188

137

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With the success of immune checkpoint inhibitors (ICIs), significant progress has been made in the field of cancer immunotherapy. Despite the long-lasting outcomes in responders, the majority of patients with cancer still do not benefit from this revolutionary therapy. Increasing evidence suggests that one of the major barriers limiting the efficacy of immunotherapy seems to coalesce with the hypoxic tumor microenvironment (TME), which is an intrinsic property of all solid tumors. In addition to its impact on shaping tumor invasion and metastasis, the hypoxic TME plays an essential role in inducing immune suppression and resistance though fostering diverse changes in stromal cell biology. Therefore, targeting hypoxia may provide a means to enhance the efficacy of immunotherapy. In this review, the potential impact of hypoxia within the TME, in terms of key immune cell populations, and the contribution to immune suppression are discussed. In addition, we outline how hypoxia can be manipulated to tailor the immune response and provide a promising combinational therapeutic strategy to improve immunotherapy.

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“…Thus, this approach might be exploited in the future to monitor the response of pseudohypoxic PCC cells to anti-angiogenic drugs in vivo. Recent studies have demonstrated the high quality of the vessel resolution by MSOT in breast cancer and its suitability to monitor drug treatment response [ 80 ], thereby suggesting that this modality might be applicable to preclinical PPGL research as well.…”

Section: Introductionmentioning

confidence: 99%

Imaging pheochromocytoma in small animals: preclinical models to improve diagnosis and treatment

et al. 2021

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Pheochromocytomas (PCCs) and paragangliomas (PGLs), together referred to as PPGLs, are rare chromaffin cell-derived tumors. They require timely diagnosis as this is the only way to achieve a cure through surgery and because of the potentially serious cardiovascular complications and sometimes life-threatening comorbidities that can occur if left untreated. The biochemical diagnosis of PPGLs has improved over the last decades, and the knowledge of the underlying genetics has dramatically increased. In addition to conventional anatomical imaging by CT and MRI for PPGL detection, new functional imaging modalities have emerged as very useful for patient surveillance and stratification for therapy. The availability of validated and predictive animal models of cancer is essential for translating molecular, imaging and therapy response findings from the bench to the bedside. This is especially true for rare tumors, such as PPGLs, for which access to large cohorts of patients is limited. There are few animal models of PPGLs that have been instrumental in refining imaging modalities for early tumor detection, as well as in identifying and evaluating novel imaging tracers holding promise for the detection and/or treatment of human PPGLs. The in vivo PPGL models mainly include xenografts/allografts generated by engrafting rat or mouse cell lines, as no representative human cell line is available. In addition, there is a model of endogenous PCCs (i.e., MENX rats) that was characterized in our laboratory. In this review, we will summarize the contribution that various representative models of PPGL have given to the visualization of these tumors in vivo and we present an example of a tracer first evaluated in MENX rats, and then translated to the detection of these tumors in human patients. In addition, we will illustrate briefly the potential of ex vivo biological imaging of intact adrenal glands in MENX rats.

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Resolution of Spatial and Temporal Heterogeneity in Bevacizumab-Treated Breast Tumors by Eigenspectra Multispectral Optoacoustic Tomography

Cited by 17 publications

References 55 publications

3D Ultrasound-Guided Photoacoustic Imaging to Monitor the Effects of Suboptimal Tyrosine Kinase Inhibitor Therapy in Pancreatic Tumors

3D Ultrasound-Guided Photoacoustic Imaging to Monitor the Effects of Suboptimal Tyrosine Kinase Inhibitor Therapy in Pancreatic Tumors

Targeting hypoxia in the tumor microenvironment: a potential strategy to improve cancer immunotherapy

Imaging pheochromocytoma in small animals: preclinical models to improve diagnosis and treatment

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