Intrathecal [64Cu]Cu-albumin PET reveals age-related decline of lymphatic drainage of cerebrospinal fluid.

Age-related cognitive decline is associated with dysfunctional lymphatic drainage of cerebrospinal fluid (CSF) through meningeal lymphatic vessels. In this study, intrathecal [64Cu]Cu-albumin positron emission tomography (PET) was applied in mice to evaluate lymphatic drainage of CSF and its variation with age. [64Cu]Cu-albumin PET was performed at multiple time points after intrathecal injection of [64Cu]Cu-albumin at an infusion rate of 700 nl/min in adult and aged mice (15-25 months old). CSF clearance and paravertebral lymph nodes were quantified after injection and during the stationary phase. Stationary phase of the next day followed the initial perturbed state by injection of 6 ul (1/7 of total CSF volume) and CSF clearance half-time from the subarachnoid space was 93.4 ± 19.7 and 123.3 ± 15.6 min in adult and aged mice (p = 0.01), respectively. While the % injected dose of CSF space were higher, the activity of the paravertebral lymph nodes were lower in the aged mice on the next day. [64Cu]Cu-albumin PET enabled us to quantify CSF-lymphatic drainage across all levels of brain spinal cords and to visualize and quantify lymph node activity due to CSF drainage. [64Cu]Cu-albumin PET revealed the age-related decrease of the lymphatic drainage of CSF due to this decreased drainage from the subarachnoid space, especially during the stationary phase, in aged mice.

Prognostic impact of an integrative analysis of [18F]FDG PET parameters and infiltrating immune cell scores in lung adenocarcinoma.

BACKGROUND: High levels of 18F-fluorodeoxyglucose (18F-FDG) tumor uptake are associated with worse prognosis in patients with non-small cell lung cancer (NSCLC). Meanwhile, high levels of immune cell infiltration in primary tumor have been linked to better prognosis in NSCLC. We conducted this study for precisely stratified prognosis of the lung adenocarcinoma patients using the integration of 18F-FDG positron emission tomography (PET) parameters and infiltrating immune cell scores as assessed by a genomic analysis. RESULTS: Using an RNA sequencing dataset, the patients were divided into three subtype groups. Additionally, 24 different immune cell scores and cytolytic scores (CYT) were obtained. In 18F-FDG PET scans, PET parameters of the primary tumors were obtained. An ANOVA test, a Chi-square test and a correlation analysis were also conducted. A Kaplan-Meier survival analysis with the log-rank test and multivariable Cox regression test was performed to evaluate prognostic values of the parameters. The terminal respiratory unit (TRU) group demonstrated lower 18F-FDG PET parameters, more females, and lower stages than the other groups. Meanwhile, the proximal inflammatory (PI) group showed a significantly higher CYT score compared to the other groups (P = .001). Also, CYT showed a positive correlation with tumor-to-liver maximum standardized uptake value ratio (TLR) in the PI group (P = .027). A high TLR (P = .01) score of 18F-FDG PET parameters and a high T follicular helper cell (TFH) score (P = .005) of immune cell scores were associated with prognosis with opposite tendencies. Furthermore, TLR and TFH were predictive of overall survival even after adjusting for clinicopathologic features and others (P = .024 and .047). CONCLUSIONS: A high TLR score was found to be associated with worse prognosis, while high CD8 T cell and TFH scores predicted better prognosis in lung adenocarcinoma. Furthermore, TLR and TFH can be used to predict prognosis independently in patients with lung adenocarcinoma.

[ 64Cu]Cu-Albumin Clearance Imaging to Evaluate Lymphatic Efflux of Cerebrospinal Space Fluid in Mouse Model.

Purpose: Clearance of brain waste in the cerebrospinal fluid (CSF) through the meningeal lymphatic vessels (mLV) has been evaluated mostly through the fluorescent imaging which has inherent limitations in the context of animal physiology and clinical translatability. The study aimed to establish molecular imaging for the evaluation of mLV clearance function. Methods: Radionuclide imaging after intrathecal (IT) injection was acquired in C57BL/6 mice of 2-9 months. The distribution of [99mTc]Tc-diethylenetriamine pentaacetate (DTPA) and [64Cu]Cu-human serum albumin (HSA) was comparatively evaluated. Evans Blue and [64Cu]Cu-HSA were used to evaluate the distribution of tracer under various speed and volume conditions. Results: [99mTc]Tc-DTPA is not a suitable tracer for evaluation of CSF clearance via mLV as no cervical lymph node uptake was observed while it was cleared from the body. A total volume of 3 to 9 µL at an infusion rate of 300 to 500 nL/min was not sufficient for the tracer to reach the cranial subarachnoid space and clear throughout the mLV. As a result, whole-body positron emission tomography imaging using [64Cu]Cu-HSA at 700 nL/min, to deliver 6 µL of injected volume, was set for characterization of the CSF to mLV clearance. Through this protocol, the mean terminal CSF clearance half-life was measured to be 123.6 min (range 117.0-135.0) in normal mice. Conclusions: We established molecular imaging to evaluate CSF drainage through mLV using [64Cu]Cu-HSA. This imaging method is expected to be extended in animal models of dysfunctional meningeal lymphatic clearance and translational research for disease-modifying therapeutic approaches. Supplementary Information: The online version contains supplementary material available at 10.1007/s13139-022-00746-6.

Brain Glymphatic/Lymphatic Imaging by MRI and PET.

Since glymphatic was proposed and meningeal lymphatic was discovered, MRI and even PET were introduced to investigate brain parenchymal interstitial fluid (ISF), cerebrospinal fluid (CSF), and lymphatic outflow in rodents and humans. Previous findings by ex vivo fluorescent microscopic, and in vivo two-photon imaging in rodents were reproduced using intrathecal contrast (gadobutrol and the similar)-enhanced MRI in rodents and further in humans. On dynamic MRI of meningeal lymphatics, in contrast to rodents, humans use mainly dorsal meningeal lymphatic pathways of ISF-CSF-lymphatic efflux. In mice, ISF-CSF exchange was examined thoroughly using an intra-cistern injection of fluorescent tracers during sleep, aging, and neurodegeneration yielding many details. CSF to lymphatic efflux is across arachnoid barrier cells over the dorsal dura in rodents and in humans. Meningeal lymphatic efflux to cervical lymph nodes and systemic circulation is also well-delineated especially in humans onintrathecal contrast MRI. Sleep- or anesthesia-related changes of glymphatic-lymphatic flow and the coupling of ISF-CSF-lymphatic drainage are major confounders ininterpreting brain glymphatic/lymphatic outflow in rodents. PET imaging in humans should be interpreted based on human anatomy and physiology, different in some aspects, using MRI recently. Based on the summary in this review, we propose non-invasive and longer-term intrathecal SPECT/PET or MRI studies to unravel the roles of brain glymphatic/lymphatic in diseases.

Theranostics in Bangladesh: Current Status, Challenges, and Future Perspective.

BACKGROUND AND CURRENT STATUS OF THERANOSTICS: Therapeutic nuclear medicine (NM) in Bangladesh began in the early 1980s with the application of radioactive iodine for treatment of thyroid cancer and primary hyperthyroidism. Since then, NM practice has remarkably developed in the country with the advancement of instrumentation, radiopharmacy, and information technology. The government took the initiative to establish four PET-CT centers at different NM centers, including one at the National Institute of Nuclear Medicine and Allied Sciences (NINMAS). A further development is the installation of a cyclotron center (18-MeV cyclotron) at NINMAS by the government's fund. Currently, NM is providing good health services to oncology patients throughout the country. More than 20 NM centers are functioning in different parts of the country, and therapeutic NM has an important place. However, conventional radioactive iodine still remains the major theranostic application. CHALLENGES AND FUTURE PERSPECTIVE: The expansion and development of therapeutic NM for other cancers have been limited due to a number of challenging factors. A brief overview of the history and current status of NM in Bangladesh is presented here with an examination of factors that pose as obstacles to the introduction and development of new therapeutic technologies. Finally, future perspectives are discussed with ways to mitigate existing problems and challenges.

Plasmablastic lymphoma exclusively involving bones mimicking osteosarcoma in an immunocompetent patient: A case report.

BACKGROUND: It has been known that plasmablastic lymphoma (PBL) is a neoplasm of immunocompromised patients occurring in soft tissue of oral cavity or in the vicinity whereas bone is an unlikely site to harbor PBL. However, its occurrence is increasingly being reported in immunocompetent individuals in either osseous or extra-oral sites. To our best knowledge, F-18 FDG PET/CT findings of PBL involving bones in an immunocompetent patient have not been reported, yet . CASE SUMMARY: We report a case of PBL involving multiple bones in an immunocompetent patient. Features of different imaging modalities including F-18 Fluoro-deoxy glucose (FDG) positron emission tomography/computed tomography (PET/CT) were correlated well as findings of osteosarcoma in mandible with metastatic lesions. However, the histopathology and immunohistochemistry (IHC) of bone tissues from 2 separate biopsy sites revealed features of PBL. CONCLUSION: awareness to F-18 FDG PET/CT findings of PBL involving bones in an immunocompetent patient may prevent misdiagnosis.

Prognostic Implications of the SUVmax of Primary Tumors and Metastatic Lymph Node Measured by 18F-FDG PET in Patients With Uterine Cervical Cancer: A Meta-analysis.

PURPOSE: We conducted a meta-analysis to evaluate the prognostic value of the SUVmax measured in pretreatment primary lesions and metastatic lymph nodes (LNs) on 18F-FDG PET scans in patients with uterine cervical cancer. METHODS: A systematic search of EMBASE and MEDLINE was performed using the keywords "positron emission tomography (PET)," "uterine cervical cancer," and "prognosis." Event-free survival and overall survival were evaluated as outcomes. The impact of SUVmax on survival was measured by the effect size of the hazard ratio (HR). RESULTS: Fourteen eligible studies including 1150 patients were analyzed. Patients with a high primary SUVmax showed a worse prognosis, with an HR of 2.66 (95% confidence interval [CI], 1.90-3.74; P < 0.00001) for adverse events and an HR of 2.45 (95% CI, 1.74-3.45; P < 0.00001) for death. Patients with high SUVmax in metastatic pelvic LN (PLN) showed a worse prognosis, with an HR of 2.92 (95% CI, 1.94-4.39; P < 0.00001) for adverse events and an HR of 2.66 (95% CI, 1.60-4.43; P = 0.0002) for SUVmax in PLN for death. In addition, high SUVmax in metastatic para-aortic LN was associated with a worse prognosis, with an HR of 4.41 (95% CI, 2.32-8.38; P < 0.00001) for death. CONCLUSIONS: Patients with uterine cervical cancer and a high SUVmax primary lesion, PLN, or para-aortic LN are at higher risk of adverse events or death.