Dataset Information

Dynamic 18F-FDG PET Lymphography for In Vivo Identification of Lymph Node Metastases in Murine Melanoma.

ABSTRACT: Positron lymphography using 18F-FDG followed by Cerenkov-guided resection of lymph nodes in healthy mice has previously been introduced by our group. Our aim in this study was to further assess the technique's potential beyond merely localizing sentinel lymph nodes. We now aimed to evaluate the potential of positron lymphography to characterize the nodes with respect to their tumor status in order to identify metastatic lymph nodes. We explored whether metastatic nodes could be distinguished from normal nodes via dynamic 18F-FDG lymphography, to then be resected under Cerenkov imaging guidance. Methods: A murine melanoma cell line highly metastatic to lymph nodes (B16F10) was implanted subcutaneously on the dorsal hind paw of C57 mice while the tumor-free contralateral leg served as an intraindividual control. A model of reactive lymph nodes after concanavalin A challenge served as an additional control to provide nonmalignant inflammatory lymphadenopathy. Dynamic PET/CT imaging was performed immediately after injection of 18F-FDG around the tumor or intracutaneously in the contralateral footpad. Furthermore, PET/CT and Cerenkov studies were performed repeatedly over time to follow the course of metastatic spread. In selected mice, popliteal lymph nodes underwent Cerenkov luminescence imaging. Hematoxylin and eosin staining was done to verify the presence of lymphatic melanoma infiltration. Results: Positron lymphography using 18F-FDG was successfully performed on tumor-bearing and non-tumor-bearing mice, as well as on controls bearing sites of inflammation; the results clearly identified the sentinel lymph node basin and delineated the lymphatic drainage. Significantly prolonged retention of activity was evident in metastatic nodes as compared with controls without tumor. On the basis of these results, the contrast in detection and identification of metastatic lymph nodes was distinct and could be used for guided lymph node resection, such as by using Cerenkov luminescence imaging. However, retention after 18F-FDG lymphography was also seen in acute inflammatory lymphadenopathy. Conclusion: In a tumor model, significantly longer retention of the radiotracer during 18F-FDG lymphography was seen in metastatic than nonmetastatic lymph nodes, allowing for differentiation between the two and for selective resection of tumor-bearing nodes using Cerenkov imaging. Inflammation can be better differentiated in a subacute state.

SUBMITTER: Lockau H

PROVIDER: S-EPMC5807531 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Dynamic <sup>18</sup>F-FDG PET Lymphography for In Vivo Identification of Lymph Node Metastases in Murine Melanoma.

Lockau Hannah H Neuschmelting Volker V Ogirala Anuja A Vilaseca Antoni A Grimm Jan J

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20170914 2

Positron lymphography using <sup>18</sup>F-FDG followed by Cerenkov-guided resection of lymph nodes in healthy mice has previously been introduced by our group. Our aim in this study was to further assess the technique's potential beyond merely localizing sentinel lymph nodes. We now aimed to evaluate the potential of positron lymphography to characterize the nodes with respect to their tumor status in order to identify metastatic lymph nodes. We explored whether metastatic nodes could be distin ...[more]

PMID: 28912145

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Project description:The lymphatic system plays a critical role in the maintenance of healthy tissues. Its function is an important indicator of the presence and extent of disease. In oncology, metastatic spread to local lymph nodes (LNs) is a strong predictor of poor outcome. Clinical methods for the visualization of LNs involve regional injection and tracking of (99m)Tc-sulfur colloid ((99m)Tc-SC) along with absorbent dyes. Intraoperatively, these techniques suffer from the requirement of administration of multiple contrast media ((99m)Tc-SC and isosulfan blue), unwieldy ?-probes, and a short effective surgical window for dyes. Preclinically, imaging of transport through the lymphatics is further hindered by the resolution of lymphoscintigraphy and SPECT. We investigated multimodal imaging in animal models using intradermal administration of (18)F-FDG for combined diagnostic and intraoperative use. PET visualizes LNs with high sensitivity and resolution and low background. Cerenkov radiation (CR) from (18)F-FDG was evaluated to optically guide surgical resection of LNs.Imaging of (18)F-FDG uptake used PET and sensitive luminescent imaging equipment (for CR). Dynamic PET was performed in both sexes and multiple strains (NCr Nude, C57BL/6, and Nu/Nu) of mice. Biodistribution confirmed the uptake of (18)F-FDG and was compared with that of (99m)Tc-SC. Verification of uptake and the ability to use (18)F-FDG CR to guide nodal removal were confirmed histologically.Intradermal injection of (18)F-FDG clearly revealed lymphatic vessels and LNs by PET. Dynamic imaging revealed rapid and sustained labeling of these structures. Biodistribution of the radiotracer confirmed the active transport of radioglucose in the lymphatics to the local LNs and over time into the general circulation. (18)F-FDG also enabled visualization of LNs through CR, even before surgically revealing the site, and guided LN resection.Intradermal (18)F-FDG can enhance the preclinical investigation of the lymphatics through dynamic, high-resolution, and quantitative tomographic imaging. Clinically, combined PET/Cerenkov imaging has significant potential as a single-dose, dual-modality tracer for diagnostics (PET/CT) and guided resection of LNs (Cerenkov optical).

Project description:ObjectivesTo compare the diagnostic accuracy of preoperative 18F-FDG PET/CT and MRI tumor markers for prediction of lymph node metastases (LNM) and aggressive disease in endometrial cancer (EC).MethodsPreoperative whole-body 18F-FDG PET/CT and pelvic MRI were performed in 215 consecutive patients with histologically confirmed EC. PET/CT-based tumor standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), and PET-positive lymph nodes (LNs) (SUVmax > 2.5) were analyzed together with the MRI-based tumor volume (VMRI), mean apparent diffusion coefficient (ADCmean), and MRI-positive LN (maximum short-axis diameter ≥ 10 mm). Imaging parameters were explored in relation to surgicopathological stage and tumor grade. Receiver operating characteristic (ROC) curves were generated yielding optimal cutoff values for imaging parameters, and regression analyses were used to assess their diagnostic performance for prediction of LNM and progression-free survival.ResultsFor prediction of LNM, MTV yielded the largest area under the ROC curve (AUC) (AUC = 0.80), whereas VMRI had lower AUC (AUC = 0.72) (p = 0.03). Furthermore, MTV > 27 ml yielded significantly higher specificity (74%, p < 0.001) and accuracy (75%, p < 0.001) and also higher odds ratio (12.2) for predicting LNM, compared with VMRI > 10 ml (58%, 62%, and 9.7, respectively). MTV > 27 ml also tended to yield higher sensitivity than PET-positive LN (81% vs 50%, p = 0.13). Both VMRI > 10 ml and MTV > 27 ml were significantly associated with reduced progression-free survival.ConclusionsTumor markers from 18F-FDG PET/CT outperform MRI markers for the prediction of LNM. MTV > 27 ml yields a high diagnostic performance for predicting aggressive disease and represents a promising supplement to conventional PET/CT reading in EC.Key points• Metabolic tumor volume (MTV) outperforms other 18F-FDG PET/CT and MRI markers for preoperative prediction of lymph node metastases (LNM) in endometrial cancer patients. • Using cutoff values for tumor volume for prediction of LNM, MTV > 27 ml yielded higher specificity and accuracy than VMRI> 10 ml. • MTV represents a promising supplement to conventional PET/CT reading for predicting aggressive disease in EC.

Project description:ObjectiveTo compare the apparent diffusion coefficient (ADC) in lymph node metastases of non-small cell lung cancer (NSCLC) patients with standardized uptake values (SUV) derived from combined 18F-fluoro-deoxy-glucose-positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI).Material and methods38 patients with histopathologically proven NSCLC (mean age 60.1 ± 9.5 y) received whole-body PET/CT (Siemens mCT™) 60 min after injection of a mean dose of 280 ± 50 MBq 18F-FDG and subsequent PET/MRI (mean time after tracer injection: 139 ± 26 min, Siemens Biograph mMR). During PET acquisition, simultaneous diffusion-weighted imaging (DWI, b values: 0, 500, 1000 s/mm²) was performed. A maximum of 10 lymph nodes per patient suspicious for malignancy were analyzed. Regions of interest (ROI) were drawn covering the entire lymph node on the attenuation-corrected PET-image and the monoexponential ADC-map. According to histopathology or radiological follow-up, lymph nodes were classified as benign or malignant. Pearson's correlation coefficients were calculated for all lymph node metastases correlating SUVmax and SUVmean with ADCmean.ResultsA total of 146 suspicious lymph nodes were found in 25 patients. One hundred lymph nodes were eligible for final analysis. Ninety-one lymph nodes were classified as malignant and 9 as benign according to the reference standard. In malignant lesions, mean SUVmax was 9.1 ± 3.8 and mean SUVmean was 6.0 ± 2.5 while mean ADCmean was 877.0 ± 128.6 x10(-5) mm²/s in PET/MRI. For all malignant lymph nodes, a weak, inverse correlation between SUVmax and ADCmean as well as SUVmean and ADCmean (r = -0.30, p<0.05 and r = -0.36, p<0.05) existed.ConclusionThe present data show a weak inverse correlation between increased glucose-metabolism and cellularity in lymph node metastases of NSCLC patients. 18F-FDG-PET and DWI thus may offer complementary information for the evaluation of treatment response in lymph node metastases of NSCLC.

Project description:ObjectivesThe accurate assessment of lymph node metastases (LNMs) and the preoperative nodal (N) stage are critical for the precise treatment of patients with gastric cancer (GC). The diagnostic performance, however, of current imaging procedures used for this assessment is sub-optimal. Our aim was to investigate the value of preoperative 18F-FDG PET/CT radiomic features to predict LNMs and the N stage.MethodsWe retrospectively collected clinical and 18F-FDG PET/CT imaging data of 185 patients with GC who underwent total or partial radical gastrectomy. Patients were allocated to training and validation sets using the stratified method at a fixed ratio (8:2). There were 2,100 radiomic features extracted from the 18F-FDG PET/CT scans. After selecting radiomic features by the random forest, relevancy-based, and sequential forward selection methods, the BalancedBagging ensemble classifier was established for the preoperative prediction of LNMs, and the OneVsRest classifier for the N stage. The performance of the models was primarily evaluated by the AUC and accuracy, and validated by the independent validation methods. Analysis of the feature importance and the correlation were also conducted. We also compared the predictive performance of our radiomic models to that with the contrast-enhanced CT (CECT) and 18F-FDG PET/CT.ResultsThere were 185 patients-127 men, 58 women, with the median age of 62, and an age range of 22-86 years. One CT feature and one PET feature were selected to predict LNMs and achieved the best performance (AUC: 82.2%, accuracy: 85.2%). This radiomic model also detected some LNMs that were missed in CECT (19.6%) and 18F-FDG PET/CT (35.7%). For predicting the N stage, four CT features and one PET feature were selected (AUC: 73.7%, accuracy: 62.3%). Of note, a proportion of patients in the validation set whose LNMs were incorrectly staged by CECT (57.4%) and 18F-FDG PET/CT (55%) were diagnosed correctly by our radiomic model.ConclusionWe developed and validated two machine learning models based on the preoperative 18F-FDG PET/CT images that have a predictive value for LNMs and the N stage in GC. These predictive models show a promise to offer a potentially useful adjunct to current staging approaches for patients with GC.

Dataset Information

Dynamic 18F-FDG PET Lymphography for In Vivo Identification of Lymph Node Metastases in Murine Melanoma.

Publications

Dynamic <sup>18</sup>F-FDG PET Lymphography for In Vivo Identification of Lymph Node Metastases in Murine Melanoma.

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