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Radionuclide Imaging in Treatment Planning
Published in W. P. M. Mayles, A. E. Nahum, J.-C. Rosenwald, Handbook of Radiotherapy Physics, 2021
Hypoxia PET imaging has been used in external-beam radiotherapy to develop the concept of the hypoxia GTV (GTVh) to improve treatment outcomes in hypoxic cells that require a higher dose to be killed (Lee et al. 2008). Low contrast in 18F-fluoromisonidazole (FMISO) imaging and the variability of intra-tumour metabolism hinder the use of static PET imaging for the differentiation of tumour phenotypes and guiding dose escalation. For FMISO studies, compartmental modelling shows promise for assessing kinetic parameters and mapping regions of normoxic, hypoxic and necrotic cells. K1 describes the rate of perfusion and k3 the trapping rate constant related to the presence of hypoxia (Wang et al. 2009). In a more recent trial, the concept of dose de-escalation was investigated for human papillomavirus (HPV)-positive oropharyngeal carcinomas. FMISO dynamic imaging demonstrated that for half of the enrolled patients, hypoxia was resolved after 1 week of treatment, enabling a lymph node dose reduction of 10 Gy (Lee et al. 2016).
Non-FDG radionuclide imaging and targeted therapies
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
Luigi Aloj, Ferdia A Gallagher
There are several PET probes for probing hypoxia, including: [18F]-fluoromisonidazole (FMISO); [18F]-fluoroazomycinarabinoside (FAZA); and diacetyl-bis(N4-methylthiosemicarbazone) (ATSM) (6). 18F-FMISO is a nitroimidazole, which passively diffuses through the cell membrane and is reduced inside the cell by nitroreductase; in the presence of oxygenation, the tracer diffuses back out into the extracellular environment. However, in the absence of oxygen it binds covalently to intracellular molecules and becomes trapped inside the cell (7). Hypoxia with 18F-FMISO has been investigated in a variety of solid tumours including gliomas, head and neck cancer, lung and breast tumours, and renal cancer. It has been used to differentiate high-grade from lower-grade gliomas (8) and has been shown to be a prognostic biomarker in high-grade gliomas (9). Hypoxia imaging with 18F-FMISO has also been used to direct intensity-modulated radiotherapy (IMRT), given the importance of free oxygen radicals for the effectiveness of radiotherapy (10). 18F-FAZA is a second-generation 2-nitroimidazole compound which has shown promising results for imaging hypoxic tumours. For example, it has been a predictor of response to therapy in a number of models and has been shown to have particularly high uptake in gliomas (11).
Recent Advances in Technology
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
Fluorinated nitromidazole compounds, including 1-[2-nitro-1-imidazolyl-3[18-F]fluoro-2-propanol [[18 F]FMISO], have been used for imaging hypoxia in H&N SqCC*. Copper isotopes of varying half-life, including 60 Cu, 61 Cu, 62 Cu and 62 Cu labelled to copper-diacetyl-bis(N4-methylthiosemicabazone) [Cu-ATSM] and copper-pyruvaldehyde-bis(N4-methylthiosemicarbazone [Cu-PTSM] have also been studied. There is as yet no one clear front runner. [18 F]FMISO is the most commonly used and best validated tracer and most studies have shown correlation between hypoxia and [18 F]FMISO uptake.91 But it is only slowly cleared from the blood compartment and the radiotracer passively diffuses into the cell which takes a relatively long time. This means that for imaging to be effective it has to be done between 2 to 3 hours post-injection.92 There are as yet inadequate data to recommend the other tracers as superior.
Hypoxic stress visualized in the cervical spinal cord of ALS patients
Published in Neurological Research, 2021
Toru Yamashita, Tetsuhiro Hatakeyama, Kota Sato, Yusuke Fukui, Nozomi Hishikawa, Mami Takemoto, Yasuyuki Ohta, Yoshihiro Nishiyama, Nobuyuki Kawai, Takashi Tamiya, Koji Abe
In the present study, we focused on hypoxic stress imaging of the cervical spinal cord in ALS patients. We then set regions of interest (ROIs) in the lateral segments of the spinal cord at three different levels (C1, C5, and T1), as previously reported [6]. The SUVmean value of 18F-FMISO uptake within each ROI was evaluated by imaging software (EV insite; PSP Corp., Tokyo, Japan). Since we expected strong asymmetries to indicate pathologic conditions of the spinal cord in ALS patients, homologous regions in the opposite spinal cord were evaluated separately. Statistical analyses were performed using a statistical software package (SPSS 22.0.0.0; IBM, Armonk, USA). Values are expressed as the mean ± SD. In the comparison of FMISO uptake potential, statistical analyses were performed using non-repeated measures ANOVA and the SNK test. Bivariate correlations between FMISO uptake potentials and the change rate of the ALS FRS-R score were examined using a single regression analysis. In all statistical analyses, significance was set to p< 0.05.
Anti-tumor effect of local injectable hydrogel-loaded endostatin alone and in combination with radiotherapy for lung cancer
Published in Drug Delivery, 2021
Na Wang, Qin Gao, Juan Tang, YiQing Jiang, LiShi Yang, XiangXiang Shi, Yue Chen, Yan Zhang, ShaoZhi Fu, Sheng Lin
Hypoxia in tumors was evaluated by measuring18FMISO uptake (Tang et al., 2019) through micro PET/CT scans one day following treatment using Inveon micro PET/CT (Siemens, Munich, Germany). The mice were injected with 50–80 mCi 18FMISO into their tail veins. After 90 min of 18FMISO administration, the mice were gas anesthetized with Isoflurane and then placed in a central PET ring field; PET/CT images were obtained using the following parameters: 80 kV, 500 mA, slice thickness 1.5 mm, and 10 min per bed position. The image plane with the largest tumor appearance was selected for analysis, and the region of interest (ROI) was manually drawn across the entire tumor. Tracer uptake values of the tumors were measured in attenuation-corrected lateral chromatographic sections by calculating standard uptake values (SUVs) measured by ROI.
Non-linear conversion of HX4 uptake for automatic segmentation of hypoxic volumes and dose prescription
Published in Acta Oncologica, 2018
Ana Ureba, Emely Lindblom, Alexandru Dasu, Johan Uhrdin, Aniek J. G. Even, Wouter van Elmpt, Philippe Lambin, Peter Wersäll, Iuliana Toma-Dasu
Several PET tracers are currently available for imaging tumour hypoxia, the most used one in the clinic being 18F-FMISO [5]. Alternatives to 18F-FMISO have however been tested, including 18F-HX4 [6], which was proposed to overcome the slow clearance kinetics of 18F-FMISO and was investigated both in preclinical and clinical studies [6–11]. Both these tracers belong to the nitromidazole family, and therefore it is expected that they have similar mechanisms for binding to hypoxic cells. Nevertheless, the relationship between the relative uptake of each tracer and the oxygen partial pressure depends on the chemical composition of the tracer and the biochemical processes through which they bind to the hypoxic cells. This relationship has been the concern for studies investigating the opportunity of targeting hypoxia based on imaging with hypoxic tracers. The relationship for FMISO and FETA has been investigated a few years back [12], but several other tracers have since appeared. A recent study has investigated the general shape of the relationship for F-HX4, but without determining the parameters of the relationship [13].