Dataset Information

Targeted PET imaging strategy to differentiate malignant from inflamed lymph nodes in diffuse large B-cell lymphoma.

ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults. DLBCL exhibits highly aggressive and systemic progression into multiple tissues in patients, particularly in lymph nodes. Whole-body 18F-fluodeoxyglucose positron emission tomography ([18F]FDG-PET) imaging has an essential role in diagnosing DLBCL in the clinic; however, [18F]FDG-PET often faces difficulty in differentiating malignant tissues from certain nonmalignant tissues with high glucose uptake. We have developed a PET imaging strategy for DLBCL that targets poly[ADP ribose] polymerase 1 (PARP1), the expression of which has been found to be much higher in DLBCL than in healthy tissues. In a syngeneic DLBCL mouse model, this PARP1-targeted PET imaging approach allowed us to discriminate between malignant and inflamed lymph nodes, whereas [18F]FDG-PET failed to do so. Our PARP1-targeted PET imaging approach may be an attractive addition to the current PET imaging strategy to differentiate inflammation from malignancy in DLBCL.

SUBMITTER: Tang J

PROVIDER: S-EPMC5594659 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Targeted PET imaging strategy to differentiate malignant from inflamed lymph nodes in diffuse large B-cell lymphoma.

Tang Jun J Salloum Darin D Carney Brandon B Brand Christian C Kossatz Susanne S Sadique Ahmad A Lewis Jason S JS Weber Wolfgang A WA Wendel Hans-Guido HG Reiner Thomas T

Proceedings of the National Academy of Sciences of the United States of America 20170821 36

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults. DLBCL exhibits highly aggressive and systemic progression into multiple tissues in patients, particularly in lymph nodes. Whole-body 18F-fluodeoxyglucose positron emission tomography ([18F]FDG-PET) imaging has an essential role in diagnosing DLBCL in the clinic; however, [18F]FDG-PET often faces difficulty in differentiating malignant tissues from certain nonmalignant tissues with high g ...[more]

PMID: 28827325

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Project description: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.

Dataset Information

Targeted PET imaging strategy to differentiate malignant from inflamed lymph nodes in diffuse large B-cell lymphoma.

Publications

Targeted PET imaging strategy to differentiate malignant from inflamed lymph nodes in diffuse large B-cell lymphoma.

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