Hypoxia 18F-FAZA PET/CT imaging in lung cancer and high-grade glioma: open issues in clinical application

Mapelli, Paola; Incerti, Elena; Bettinardi, Valentino; Conte, Gian Marco; Fallanca, Federico; Bailo, Michele; Vuozzo, Marta; Callea, Marcella

doi:10.1007/s40336-017-0240-0

Cited by 10 publications

(5 citation statements)

References 27 publications

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“…In order to reach this goal, MRI and 18F-FAZA PET/CT images were coregistered to identify the areas of both high-perfusion MRI markers and high 18F-FAZA uptake, and therefore guide the bioptic sampling on the most representative tumor region (Figure 1). 15 The treatment of choice in high-grade glioma is represented by radical radiotherapy and concomitant . The brain lesion showed 18F-FAZA uptake with a central photopenic area, possibily due to necrotic tissue, on PET images (e).…”

Section: Resultsmentioning

confidence: 99%

“…MRI and 18F-FAZA PET/CT images were then co-registered and an area of both high-perfusion MRI markers and high 18F-FAZA uptake was selected for biopsy after appropriate image fusion (f) to select the most representative tumor region to be sampled. 15 18F-FAZA: 18F-flouroazomycin arabinoside; CT: computed tomography; MRI: magnetic resonance imaging; PET: positron emission tomography.…”

Section: Resultsmentioning

confidence: 99%

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18F-FAZA PET imaging in tumor hypoxia: A focus on high-grade glioma

Mapelli

2020

Int J Biol Markers

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The presence of hypoxia is a typical feature of solid tumors and has been identified in many neoplasms, favouring the survival of malignant cells in a hostile environment and the expression of an aggressive phenotype. Malignant brain tumors have large proportions of hypoxic tissue, thus contributing to resistance to radiation and chemotherapy. Positron emission tomography (PET) is an attractive technique to gain a non-invasive assessment of tumor hypoxia within the whole tumor, with 18F-fluoromisonidazole (18F-FMISO) and 18F-flouroazomycin arabinoside (18F-FAZA) being the most promising radiotracers. In this short review, we aim to discuss the available clinical studies focused on the use of 18F-FAZA PET/computed tomography in patients affected by high-grade glioma.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

18F-FAZA PET imaging in tumor hypoxia: A focus on high-grade glioma

Mapelli

2020

Int J Biol Markers

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“…Despite these limitations, based on the results of the present study and considering the very well-known heterogeneity characterising HGG at metabolic, molecular and genetic level, a noninvasive method able to provide a whole characterisation of hypoxia intratumor heterogeneity, such as 18 F-FAZA PET/CT, might be strategically essential for diagnostic and therapeutic targeting [31,32]. This is particularly true for radiotherapy treatment, as some studies have already started to suggest the potential relevance of hypoxia imaging in guiding bioptic sampling and radiotherapy treatment [5,6,33].…”

Section: Discussionmentioning

confidence: 99%

“…In order to non-invasively define the tumour regions with a higher degree of hypoxia, the use of reliable imaging modalities is advocate, as this approach might improve the diagnostic work-up by guiding specific bioptic sampling and by supporting radiation treatment planning with the delivery of higher doses on the most hypoxic tumour regions [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

18F-FAZA PET/CT in pretreatment assessment of hypoxic status in high-grade glioma: correlation with hypoxia immunohistochemical biomarkers

Mapelli

Callea²,

Fallanca³

et al. 2021

Nuclear Medicine Communications

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Background To investigate the correlation between 18F-labeled fluoroazomycinarabinoside (18F-FAZA) PET data and hypoxia immunohistochemical markers in patients with high-grade glioma (HGG). Patients and methods Prospective study including 20 patients with brain MRI suggestive for HGG and undergoing 18F-FAZA PET/CT before treatment for hypoxia assessment. For each 18F-FAZA PET scan SUVmax, SUVmean and 18F-FAZA tumour volume (FTV) at 40, 50 and 60% threshold of SUVmax were calculated; hypoxic volume was estimated by applying different thresholds (1.2, 1.3 and 1.4) to tumour/blood ratio. Seventeen patients were analysed. The immunohistochemical analysis assessed the following parameters: hypoxia-inducible factor 1α, carbonic anhydrase IX (CA-IX), glucose transporter-1, tumour vascularity and Ki-67. Results 18F-FAZA PET showed a single lesion in 15/17 patients and multiple lesions in 2/17 patients. Twelve/17 patients had grade IV glioma and 5/17 with grade III glioma. Bioptic and surgical samples have been analysed separately. In the surgical subgroup (n = 7) a positive correlation was observed between CA-IX and SUVmax (P = 0.0002), SUVmean40 (P = 0.0058), SUVmean50 (P = 0.009), SUVmean60 (P = 0.0153), FTV–40–50–60 (P = 0.0424) and hypoxic volume1.2–1.3–1.4 (P = 0.0058). In the bioptic group (n = 10) tumour vascularisation was inversely correlated with SUVmax (P = 0.0094), SUVmean40 (P = 0.0107), SUVmean50 (P = 0.0094) and SUVmean60 (P = 0.0154). Conclusions The correlation of 18F-FAZA PET parameters with CD31 and CA-IX represents a reliable method for assessing tumour hypoxia in HGG. The inverse correlation between tumour vascularisation, SUVmax and SUVmean suggest that highly vascularized tumours might present more oxygen supply than hypoxia.

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“…18 F is one of the most important radionuclides for PET imaging, and it causes low amounts of radiation side effect to the human body because of its suitable half-life ( t 1/2 , 109.7 min). Currently, many 18 F-labeled 2-nitroimidazole derivatives have been prepared for studying hypoxia in tumors. − The representative 18 F-labeled 2-nitroimidazole derivative is [ 18 F]FMISO, which has been used to detect tumor clinically. However, [ 18 F]FMISO is limited by its drawbacks, such as the low ratio between the radioactivity in the hypoxic tissue and in the background tissue, high lipophilicity, long blood retention time, and high radioactivity concentration in the digestive tract; thus, further improvements are required for effective imaging .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Bioevaluation of Novel [¹⁸F]FDG-Conjugated 2-Nitroimidazole Derivatives for Tumor Hypoxia Imaging

et al. 2019

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Hypoxia imaging can guide tumor treatment and monitor changes in hypoxia during treatment. However, there is still no ideal hypoxia imaging agent for clinical applications. In this study, two novel 2-nitromidazole derivatives were synthesized and directly radiolabeled by [18F]FDG in high radiochemical yield and excellent radiochemical purity. Cell experiments, biodistribution, and positron emission tomography (PET) imaging studies were also conducted in mice-bearing S180 or OS732 tumors. [18F]FDG-2NNC2ON [(2R,3S,4R,E)-2-18F-fluoro-3,4,5,6-tetrahydroxyhexanal O-3-(2-(2-nitro-1H-imidazole-1-yl)ethylamino)-2-oxopropyl oxime] and [18F]FDG-2NNC5ON [(2R,3S,4R,E)-2-18F-fluoro-3,4,5,6-tetrahydroxyhexanal-O-3-(5-(2-nitro-1H-imidazole-1-yl)pentylamino)-2-oxopropyl oxime] can be cleared from the blood quickly and specifically target hypoxic tumor cells. The uptake of the probes by hypoxic cells gradually increases with time. After 4 h, the uptake value of [18F]FDG-2NNC2ON in hypoxic cells is 3.2 times higher than that in normoxia cells. In contrast, there is no difference in the uptake of [18F]FDG between hypoxic cells and normoxia cells. Biodistribution resulting from two tumor models indicate that the uptake values of the two radiotracers in the tumor are higher at 1 h than those at 2 and 4 h. At 1 and 2 h, the tumors are clearly observed on the PET images and the imaging features of [18F]FDG-2NNC5ON and [18F]FDG-2NNC2ON are distinct from those of [18F]FDG. Compared with [18F]FDG-2NNC5ON, [18F]FDG-2NNC2ON has a higher proportion of renal excretion, lower digestive tract uptake, and better imaging contrast because of its higher hydrophilicity. At 2 h, [18F]FDG-2NNC2ON shows a good tumor-to-blood (T/B) ratio, tumor-to-muscle ratio based on biodistribution (Bio-T/M ratio), and tumor-to-muscle ratio based on regions of interest on the PET images [region of interest (ROI)-T/M ratio] in the two tumor models (T/B, Bio-T/M, and ROI-T/M ratios are 3.2, 2.6, and 3.9 in the S180 tumor model and are 3.4, 4.2, and 4.6 in the OS732 tumor model, respectively). The imaging features visualized with autoradiography mostly coincided with the positive areas of HIF1α staining by immunofluorescence. Meanwhile, the biodistribution study and PET imaging revealed that the uptake of the radiotracers in the tumor cannot be competed by 5% glucose, confirming that [18F]FDG-2NNC2ON targets the hypoxic regions of the tumors instead of targeting tumors through the glucose metabolism pathway. These results suggest that the new 2-nitroimidazole derivative conjugated with [18F]FDG, [18F]FDG-2NNC2ON, has potential as an imaging agent for hypoxia.

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Hypoxia 18F-FAZA PET/CT imaging in lung cancer and high-grade glioma: open issues in clinical application

Cited by 10 publications

References 27 publications

18F-FAZA PET imaging in tumor hypoxia: A focus on high-grade glioma

18F-FAZA PET imaging in tumor hypoxia: A focus on high-grade glioma

18F-FAZA PET/CT in pretreatment assessment of hypoxic status in high-grade glioma: correlation with hypoxia immunohistochemical biomarkers

Synthesis and Bioevaluation of Novel [¹⁸F]FDG-Conjugated 2-Nitroimidazole Derivatives for Tumor Hypoxia Imaging

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Hypoxia 18F-FAZA PET/CT imaging in lung cancer and high-grade glioma: open issues in clinical application

Cited by 10 publications

References 27 publications

18F-FAZA PET imaging in tumor hypoxia: A focus on high-grade glioma

18F-FAZA PET imaging in tumor hypoxia: A focus on high-grade glioma

18F-FAZA PET/CT in pretreatment assessment of hypoxic status in high-grade glioma: correlation with hypoxia immunohistochemical biomarkers

Synthesis and Bioevaluation of Novel [18F]FDG-Conjugated 2-Nitroimidazole Derivatives for Tumor Hypoxia Imaging

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Synthesis and Bioevaluation of Novel [¹⁸F]FDG-Conjugated 2-Nitroimidazole Derivatives for Tumor Hypoxia Imaging