scholarly journals Longitudinal PET Imaging to Monitor Treatment Efficacy by Liposomal Irinotecan in Orthotopic Patient-Derived Pancreatic Tumor Models of High and Low Hypoxia

2019 ◽  
Vol 22 (3) ◽  
pp. 653-664
Author(s):  
Manuela Ventura ◽  
Nicholas Bernards ◽  
Raquel De Souza ◽  
Inga B. Fricke ◽  
Bart S. Hendriks ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Treatment Efficacy ◽  
Tumor Volume ◽  
Tumor Hypoxia ◽  
Tumor Model ◽  
Volume Control ◽  
Pancreatic Tumors ◽  
Tumor Models ◽  
Positron Emission ◽  
Liposomal Irinotecan

Abstract Purpose Hypoxia is linked to aggressiveness, resistance to therapy, and poor prognosis of pancreatic tumors. Liposomal irinotecan (nal-IRI, ONIVYDE®) has shown potential in reducing hypoxia in the HT29 colorectal cancer model, and here, we investigate its therapeutic activity and ability to modulate hypoxia in patient-derived orthotopic tumor models of pancreatic cancer. Procedures Mice were randomized into nal-IRI treated and untreated controls. Magnetic resonance imaging was used for monitoring treatment efficacy, positron emission tomography (PET) imaging with F-18-labelled fluoroazomycinarabinoside ([18F]FAZA) for tumor hypoxia quantification, and F-18-labelled fluorothymidine ([18F]FLT) for tumor cell proliferation. Results The highly hypoxic OCIP51 tumors showed significant response following nal-IRI treatment compared with the less hypoxic OCIP19 tumors. [18F]FAZA-PET detected significant hypoxia reduction in treated OCIP51 tumors, 8 days before significant changes in tumor volume. OCIP19 tumors also responded to therapy, although tumor volume control was not accompanied by any reduction in [18F]FAZA uptake. In both models, no differences were observable in [18F]FLT uptake in treated tumors compared with control mice. Conclusions Hypoxia modulation may play a role in nal-IRI’s mechanism of action. Nal-IRI demonstrated greater anti-tumor activity in the more aggressive and hypoxic tumor model. Furthermore, hypoxia imaging provided early prediction of treatment response.

scholarly journals Early Detection of Response to Radiotherapy Treatment with 11C-Acetate PET Imaging

2021 ◽  
pp. 1-3
Author(s):  
M'hamed Bentourkia ◽  
Redha alla Abdo ◽  
Chang Shu Wang ◽  
Eric Lavallee ◽  
Francois Lessard ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Pet Imaging ◽  
Tumor Volume ◽  
Compartment Model ◽  
Tumor Perfusion ◽  
Positron Emission ◽  
Early Treatment Response ◽  
Pre Treatment ◽  
Radiotherapy Dose ◽  
Radiotherapy Treatment

11C-Acetate radiotracer with Positron Emission Tomography (PET) imaging is currently used in cardiovascular imaging for perfusion and oxygen consumption measurement. It is also used, among other diseases, for prostate cancer as this radiotracer does not accumulate in the bladder. The present study reports the assessment of the radiotherapy treatment by measuring the tumor perfusion and oxygenation before and at mid-treatment by imaging with dynamic 11C-Acetate in patients with head and neck cancer. A pre-treatment dynamic 11C-Acetate and a clinical static 18F-FDG PET were conducted before initiation of the treatment, and the second 11C-Acetate dynamic scan was performed after four weeks of radiotherapy (i.e., after a dose of 35 Gy for a total of 70 Gy). The two-tissue compartment model was applied to 11C-Acetate images to extract the perfusion and oxygen consumption. The results showed a reduction in tumor volume by more than 50% compared to the initial volume in patient-1. Besides, patient-2 has displayed a more reduced tumor volume after 4 weeks of treatment. The 11C-Acetate rate constant k2 representing oxygen consumption increased after radiotherapy dose in both patients. This increase of k2 could reflect the reoxygenation process inside the tumor, and it can reflect the early treatment response. In conclusion, 11C-Acetate could predict the early changes in the tumor perfusion and the oxidative metabolism to optimally adjust the treatment.

scholarly journals In Vivo Imaging of Hypoxia and Neoangiogenesis in Experimental Syngeneic Hepatocellular Carcinoma Tumor Model Using Positron Emission Tomography

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Adrienn Kis ◽  
Judit P. Szabó ◽  
Noémi Dénes ◽  
Adrienn Vágner ◽  
Gábor Nagy ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Positron Emission Tomography ◽  
Pet Imaging ◽  
Tumor Model ◽  
Temporal Changes ◽  
Receptor Expression ◽  
Emission Tomography ◽  
Positron Emission ◽  
Angiogenic Markers

Introduction. Hypoxia-induced ανβ3 integrin and aminopeptidase N (APN/CD13) receptor expression play an important role in tumor neoangiogenesis. APN/CD13-specific 68Ga-NOTA-c(NGR), ανβ3 integrin-specific 68Ga-NODAGA-[c(RGD)]2, and hypoxia-specific 68Ga-DOTA-nitroimidazole enable the in vivo detection of the neoangiogenic process and the hypoxic regions in the tumor mass using positron emission tomography (PET) imaging. The aim of this study was to evaluate whether 68Ga-NOTA-c(NGR) and 68Ga-DOTA-nitroimidazole allow the in vivo noninvasive detection of the temporal changes of APN/CD13 expression and hypoxia in experimental He/De tumors using positron emission tomography. Materials and Methods. 5×106 hepatocellular carcinoma (He/De) cells were used for the induction of a subcutaneous tumor model in Fischer-344 rats. He/De tumor-bearing animals were anaesthetized, and 90 min after intravenous injection of 10.2±1.1 MBq 68Ga-NOTA-c(NGR) or 68Ga-NODAGA-[c(RGD)]2 (as angiogenesis tracers) or 68Ga-DOTA-nitroimidazole (for hypoxia imaging), whole-body PET/MRI scans were performed. Results. Hypoxic regions and angiogenic markers (αvβ3 integrin and APN/CD13) were determined using 68Ga-NOTA-c(NGR), 68Ga-DOTA-nitroimidazole, and 68Ga-NODAGA-[c(RGD)]2 in subcutaneously growing He/De tumors in rats. 68Ga-NOTA-c(NGR) showed the strong APN/CD13 positivity of He/De tumors in vivo, by which observation was confirmed by western blot analysis. By the qualitative analysis of PET images, heterogenous accumulation was found inside He/De tumors using all radiotracers. Significantly (p≤0.01) higher SUVmean and SUVmax values were found in the radiotracer avid regions of the tumors than those of the nonavid areas using hypoxia and angiogenesis-specific radiopharmaceuticals. Furthermore, a strong correlation was found between the presence of angiogenic markers, the appearance of hypoxic regions, and the tumor volume using noninvasive in vivo PET imaging. Conclusion. 68Ga-DOTA-nitroimidazole and 68Ga-NOTA-c(NGR) are suitable diagnostic radiotracers for the detection of the temporal changes of hypoxic areas and neoangiogenic molecule (CD13) expression, which vary during tumor growth in a hepatocellular carcinoma model.

A quantitative LC–MS/MS approach for monitoring 2′-fluoro-2′-deoxy-D-glucose uptake in tumor tissue

Bioanalysis ◽  
2021 ◽  
Author(s):  
Wenlin Li ◽  
Cathy Zhang ◽  
Nanni Huser ◽  
Chad Ray ◽  
Scott Fountain ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Fdg Pet ◽  
Tumor Model ◽  
Cost Effective ◽  
Mouse Tumor ◽  
Internal Standards ◽  
Positron Emission ◽  
Imaging Results ◽  
Noninvasive Biomarker ◽  
Selection Of

Purpose: Develop a quantitative LC–MS/MS method for FDG, FDG-monophosphate, glucose and glucose-monophosphate in mouse tumor models to assist in validating the use of [18F]FDG-positron emission tomography (PET) imaging for anticancer therapies in a clinical setting. Methodology/results: Analytes were isolated from tumors by protein precipitation and detected on a Sciex API-5500 mass spectrometer. Improved assay robustness and selectivity were achieved through chromatographic separation of FDG-monophosphate from glucose-monophosphate, selection of a unique ion transition and incorporation of stable isotope labeled internal standards. In a mouse JIMT-1 tumor model, FDG-monophosphate levels measured by LC–MS/MS correlated with [18F]FDG-PET imaging results. Conclusion: LC–MS/MS analysis of FDG-monophosphate accumulation in tumors is a cost-effective tool to gauge the translational potential of [18F]FDG-PET imaging as a noninvasive biomarker in clinical studies.

Imaging of hypoxic lesions in patients with gliomas by using positron emission tomography with 1-(2-[18F] fluoro-1-[hydroxymethyl]ethoxy)methyl-2-nitroimidazole, a new 18F-labeled 2-nitroimidazole analog

2010 ◽  
Vol 113 (2) ◽  
pp. 358-368 ◽  
Author(s):  
Ichiyo Shibahara ◽  
Toshihiro Kumabe ◽  
Masayuki Kanamori ◽  
Ryuta Saito ◽  
Yukihiko Sonoda ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Pet Imaging ◽  
Mr Spectroscopy ◽  
Anaplastic Astrocytoma ◽  
Hypoxia Inducible Factor ◽  
Tumor Hypoxia ◽  
Radical Resection ◽  
Diffuse Astrocytoma ◽  
Proton Mr Spectroscopy ◽  
Positron Emission

Object Assessment of hypoxic conditions in brain tumors is important for predicting tumor aggressiveness and treatment response. A new hypoxia imaging agent, 1-(2-[18F]fluoro-1-[hydroxymethyl]ethoxy)methyl-2-nitroimidazole (FRP-170), with higher image contrast and faster clearance than preexisting hypoxia tracers for PET, was used to visualize hypoxic tissues in 8 patients with glioma. Methods The FRP-170 was injected and PET imaging was performed 2 hours later in 8 patients, including 3 with glioblastoma multiforme, 2 with oligodendroglioma, and 1 each with diffuse astrocytoma, anaplastic ganglioglioma, and recurrent anaplastic astrocytoma. All 8 patients also underwent MR imaging, and some patients underwent [11C]methionine or [18F]fluorodeoxyglucose PET, and proton MR spectroscopy for comparison. Tissues obtained at biopsy or radical resection were immunostained with hypoxia-inducible factor–1α (HIF-1α) antibody for the confirmation of hypoxia, except in the patient with recurrent anaplastic astrocytoma who was treated using Gamma Knife surgery. Results The FRP-170 PET images showed marked uptake with upregulation of HIF-1α in the 3 glioblastomas multiforme, and moderate uptake in the recurrent anaplastic astrocytoma and one oligodendroglioma, but no uptake in the other tumors. The FRP-170 PET images showed positive correlation with HIF-1α immunoreactivity and some correlation with FDG PET and MR imaging enhancement, but no correlation with [11C]methionine PET. Imaging with FRP-170 PET seemed to be more sensitive for detecting hypoxia than identifying the lactate peak on proton MR spectroscopy. Conclusions Imaging with FRP-170 PET can visualize hypoxic lesions in patients with glioma, as confirmed by histological examination. This new method can assess tumor hypoxia preoperatively and noninvasively.

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