1.
Neuroinflammation and immunoregulation in glioblastoma and brain metastases: Recent developments in imaging approaches.
Roesler, R, Dini, SA, Isolan, GR
Clinical and experimental immunology. 2021;(3):314-324
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Abstract
Brain tumors and brain metastases induce changes in brain tissue remodeling that lead to immunosuppression and trigger an inflammatory response within the tumor microenvironment. These immune and inflammatory changes can influence invasion and metastasis. Other neuroinflammatory and necrotic lesions may occur in patients with brain cancer or brain metastases as sequelae from treatment with radiotherapy. Glioblastoma (GBM) is the most aggressive primary malignant brain cancer in adults. Imaging methods such as positron emission tomography (PET) and different magnetic resonance imaging (MRI) techniques are highly valuable for the diagnosis and therapeutic evaluation of GBM and other malignant brain tumors. However, differentiating between tumor tissue and inflamed brain tissue with imaging protocols remains a challenge. Here, we review recent advances in imaging methods that have helped to improve the specificity of primary tumor diagnosis versus evaluation of inflamed and necrotic brain lesions. We also comment on advances in differentiating metastasis from neuroinflammation processes. Recent advances include the radiosynthesis of 18 F-FIMP, an L-type amino acid transporter 1 (LAT1)-specific PET probe that allows clearer differentiation between tumor tissue and inflammation compared to previous probes, and the combination of different advanced imaging protocols with the inclusion of radiomics and machine learning algorithms.
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Value of 18F-FDG-PET to predict PD-L1 expression and outcomes of PD-1 inhibition therapy in human cancers.
Kaira, K, Kuji, I, Kagamu, H
Cancer imaging : the official publication of the International Cancer Imaging Society. 2021;(1):11
Abstract
Anti-programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) antibodies are administered in varied human cancer types. The expression of PD-L1 within tumor cells has been identified as a predictive marker, although assessing its expression has benefitted only patients with non-small cell lung cancer (NSCLC) or head and neck cancer. Whereas, more than 75% of the patients with NSCLC showing partial response to PD-1 blockade therapy experienced long-term survival for more than 5-years Thus, identifying the responders to PD-1 blockade at early phase after its initiation is of clinical importance. The 2-deoxy-2-[fluorine-18] fluoro-D-glucose (18F-FDG) on positron emission tomography (PET) can evaluate any tumor shrinkage by assessing the metabolic tumor volume at an earlier phase than conventional modalities such as computed tomography (CT). While several reports describe the correlation of PD-L1 expression with 18F-FDG uptake rate in the tumor cells, it remains to be delineated whether this rate determined by the glucose metabolism and hypoxia is associated with the status of immune microenvironment, including the expression of PD-L1. Moreover, details of the relationship between expression of PD-L1 and 18F-FDG uptake is still unclear. Therefore, we reviewed the clinical significance of 18F-FDG uptake on PET as a predictor of the efficacy of PD-1 blockade therapy, by correlating with the expression of PD-L1, in patients with several neoplasms.
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Current Landscape and Emerging Fields of PET Imaging in Patients with Brain Tumors.
Werner, JM, Lohmann, P, Fink, GR, Langen, KJ, Galldiks, N
Molecules (Basel, Switzerland). 2020;(6)
Abstract
The number of positron-emission tomography (PET) tracers used to evaluate patients with brain tumors has increased substantially over the last years. For the management of patients with brain tumors, the most important indications are the delineation of tumor extent (e.g., for planning of resection or radiotherapy), the assessment of treatment response to systemic treatment options such as alkylating chemotherapy, and the differentiation of treatment-related changes (e.g., pseudoprogression or radiation necrosis) from tumor progression. Furthermore, newer PET imaging approaches aim to address the need for noninvasive assessment of tumoral immune cell infiltration and response to immunotherapies (e.g., T-cell imaging). This review summarizes the clinical value of the landscape of tracers that have been used in recent years for the above-mentioned indications and also provides an overview of promising newer tracers for this group of patients.
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Differentiation of benign and malignant lymph nodes in pediatric patients on ferumoxytol-enhanced PET/MRI.
Muehe, AM, Siedek, F, Theruvath, AJ, Seekins, J, Spunt, SL, Pribnow, A, Hazard, FK, Liang, T, Daldrup-Link, H
Theranostics. 2020;(8):3612-3621
Abstract
The composition of lymph nodes in pediatric patients is different from that in adults. Most notably, normal lymph nodes in children contain less macrophages. Therefore, previously described biodistributions of iron oxide nanoparticles in benign and malignant lymph nodes of adult patients may not apply to children. The purpose of our study was to evaluate if the iron supplement ferumoxytol improves the differentiation of benign and malignant lymph nodes in pediatric cancer patients on 18F-FDG PET/MRI. Methods: We conducted a prospective clinical trial from May 2015 to December 2018 to investigate the value of ferumoxytol nanoparticles for staging of children with cancer with 18F-FDG PET/MRI. Ferumoxytol is an FDA-approved iron supplement for the treatment of anemia and has been used "off-label" as an MRI contrast agent in this study. Forty-two children (7-18 years, 29 male, 13 female) received a 18F-FDG PET/MRI at 2 (n=20) or 24 hours (h) (n=22) after intravenous injection of ferumoxytol (dose 5 mg Fe/kg). The morphology of benign and malignant lymph nodes on ferumoxytol-enhanced T2-FSE sequences at 2 and 24 h were compared using a linear regression analysis. In addition, ADCmean-values, SUV-ratio (SUVmax lesion/SUVmean liver) and R2*-relaxation rate of benign and malignant lymph nodes were compared with a Mann-Whitney-U test. The accuracy of different criteria was assessed with a receiver operating characteristics (ROC) curve. Follow-up imaging for at least 6 months served as the standard of reference. Results: We examined a total of 613 lymph nodes, of which 464 (75.7%) were benign and 149 (24.3%) were malignant. On ferumoxytol-enhanced T2-FSE images, benign lymph nodes showed a hypointense hilum and hyperintense parenchyma, while malignant lymph nodes showed no discernible hilum. This pattern was not significantly different at 2 h and 24 h postcontrast (p=0.82). Benign and malignant lymph nodes showed significantly different ferumoxytol enhancement patterns, ADCmean values of 1578 and 852 x10-6 mm2/s, mean SUV-ratios of 0.5 and 2.8, and mean R2*-relaxation rate of 127.8 and 84.4 Hertz (Hz), respectively (all p<0.001). The accuracy of ADCmean, SUV-ratio and pattern (area under the curve (AUC): 0.99; 0.98; 0.97, respectively) was not significantly different (p=0.07). Compared to these three parameters, the accuracy of R2* was significantly lower (AUC: 0.93; p=0.001). Conclusion: Lymph nodes in children show different ferumoxytol-enhancement patterns on MRI than previously reported for adult patients. We found high accuracy (>90%) of ADCmean, SUV-ratio, pattern, and R2* measurements for the characterization of benign and malignant lymph nodes in children. Ferumoxytol nanoparticle accumulation at the hilum can be used to diagnose a benign lymph node. In the future, the delivery of clinically applicable nanoparticles to the hilum of benign lymph nodes could be harnessed to deliver theranostic drugs for immune cell priming.