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Functional imaging and emerging techniques in MRI
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
Roberto García-Figueiras, Anwar Padhani, Sandra Baleato-González
Tumour hypoxia leads to treatment resistance and enhanced tumour progression and has an impact on patient prognosis and survival in cancer. Hypoxia changes gene expression patterns, leading to more aggressive tumour behaviour and causing resistance to radiation and chemotherapy (100). Blood oxygenation level-dependent (BOLD)-MRI may provide a non-invasive means of assessing in vivo tumour oxygenation based on endogenous deoxyhaemoglobin as a contrast agent (101).
Introduction to Bioresponsive Polymers
Published in Deepa H. Patel, Bioresponsive Polymers, 2020
Deepa H. Patel, Drashti Pathak, Neelang Trivedi
Various diseases such as cancer, cardiomyopathy, ischemia, rheumatoid arthritis, and vascular diseases are normally associated with hypoxia [90]. Tumor hypoxia is usually measured as a negative prognostic as of its essential role in tumor progression and therapy resistance, and has been widely exploited for manufacturing diagnostic agents and therapeutics [91]. Nitroaromatic derivatives that can be converted to hydrophilic-aminoimidazoles under hypoxic circumstances with a relatively high sensitivity are amongst the most extensively exploited functional motifs for hypoxia imaging and the design of bioreductive prodrugs. Likewise, azobenzene (AZO), alternative firm, hypoxia-sensitive motif formerly used as an imaging probe, has been fused in the form of a bioreductive linker for targeted siRNA delivery [92]. In recent times, investigators also used the knowledge of engineering smart delivery systems comprising oxygen-sensitive groups as alternatives for hypoxia-sensitive small molecules to increase the sensitivity and specificity for in vivo imaging [93, 94]. For instance, ultrasensitive detection of cancer cells, a water-soluble macromolecular imaging probe with hypoxia-sensitivity and near-infrared (NIR) emission was manufactured by conjugating a phosphorescent iridium (iii) complex to a hydrophilic polymer, poly(N-vinylpyrrolidone) (PVP) [94]. Related methods might be of interest for improving imaging for the diagnosis and real-time observings of other hypoxia-associated diseases, such as stroke and ischemia [95, 96].
Molecular Imaging in Individualized Cancer Management
Published in Brian Leyland-Jones, Pharmacogenetics of Breast Cancer, 2020
David M. Schuster, Diego R. Martin
Tumor hypoxia may result in resistance to therapy. [18F]Fluoromisonidazole-3-fluoro-1-(2'-nitro-l'-imidazolyl)-2-propanol ([18F]MISO) and Cu-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) radiotracers for PET and blood oxygen level-dependent (BOLD) MRI are some of the techniques being utilized for in vivo imaging but require further study (80,81).
Is hepatocellular carcinoma complicated with portal vein tumor thrombosis potentially curable by radiotherapy in the form of stereotactic body radiation therapy?
Published in International Journal of Radiation Biology, 2022
Astha Srivastava, Haresh Kunhi Parambath, Anjali V. Ramdulari, Harsh Saxena, Rishabh Kumar, Suyash Pandey, Subhash Gupta, Babban Jee
It has been shown that tumor hypoxia reduces the effectiveness of radiation therapy. There are two types of hypoxia: acute and chronic (Brinkman et al. 2012). Radiation fractionation, which allows the surviving cells to be reoxygenated between fractions, can counteract transient hypoxia during radiation therapy. Hypoxic cells may occasionally prove to be critical targets for radiosensitizers during SBRT because the benefits of fractionation for reoxygenation are believed to be maximized after about seven fractionations. Tumor hypoxia can significantly impact the course of cancer, either directly by allowing tumor cells to spread or indirectly by stimulating angiogenesis and thereby causing tumor regrowth. Tumor multiplication and regrowth after treatment are dependent on specific cell populations within tumors. There is evidence that cells in hypoxic tumor sites, those with increased DNA repair, and those in quiescence are resistant to radiotherapy (Brinkman et al. 2012; Popp et al. 2016), SBRT resistance may develop as a result of these factors.
Hypoxia-activated prodrug derivatives of anti-cancer drugs: a patent review 2006 – 2021
Published in Expert Opinion on Therapeutic Patents, 2022
Emilie Anduran, Ludwig J Dubois, Philippe Lambin, Jean-Yves Winum
This review mainly focuses on related key patents from 2006 to 2021 of hypoxia-activated prodrug of anticancer agents. Tumor hypoxia poses a formidable challenge to therapeutic intervention. In recent years, several patent applications have been filed, showing that pharmaceutical companies and academic groups, essentially from China, were and are still very active in this field (Table 1). In the large number of HAP compounds described, the nitro (hetero)aromatic triggers are always considered as the best structural feature to achieve bioreductive properties. The majority of reported HAP compounds demonstrated better pharmacological properties compared to the parent anti-cancer compounds. Several in vitro and in vivo studies indicate hypoxia selectivity and therapeutic efficacy. To the best of our knowledge, except for the case of evofosfamide and tarloxotinib bromide, none of these HAP derivatives are currently in clinical trials, and it remains to be shown if these compounds are safe and effective. Companion diagnostics remain important for proper patient selection and to provide evidence of drug efficacy at early time points utilizing window-of-opportunity trials. In essence, the number of patent applications in the field of HAP emphasizes the hope that the exploitation of tumor hypoxia is still a promising area.
Perfusion CT radiomics as potential prognostic biomarker in head and neck squamous cell carcinoma
Published in Acta Oncologica, 2019
M. Bogowicz, S. Tanadini-Lang, P. Veit-Haibach, M. Pruschy, S. Bender, A. Sharma, M. Hüllner, G. Studer, S. Stieb, H. Hemmatazad, S. Glatz, M. Guckenberger, O. Riesterer
Head and neck cancer (HNC) is a biologically heterogenous disease, and therefore, prognostic biomarkers are warranted to individually tailor treatment. One of the most robust prognostic factors in HNC, besides human papilloma virus (HPV)-mediated carcinogenesis, is tumor hypoxia [1–7]. Therefore, a noninvasive determination of hypoxia is of special interest. Positron emission tomography (PET) imaging has been used in clinical studies for the noninvasive pretreatment evaluation of tumor hypoxia. Clinical studies have shown that the uptake of PET hypoxia tracers (18F-FMISO and 18F-FAZA) correlates with disease-free survival [8,9]. However, the availability of advanced PET tracers is limited in many centers. An alternative imaging technique for assessing tumor angiogenesis is computed tomography perfusion (CTP). It was shown to correlate to microvessel density in prostate and colorectal cancer [10,11]. There are three main perfusion parameters: blood flow (BF), blood volume (BV) and mean transit time (MTT) [12]. The CTP parameters were observed to correlate with RECIST criteria in head and neck cancer [13]. Another group failed to show a link between perfusion and tumor response, but investigated only a small cohort of 15 patients [14].