Correlation between remnant thyroid gland I-131 uptake and serum thyroglobulin levels: can we rely on I-131 whole body scans?

BACKGROUND: I-131 treatment (RAI) decision relies heavily on serum thyroglobulin (Tg) levels, as higher Tg levels are assumed to be correlated with higher I-131 uptake. Tg elevation, negative iodine scintigraphy (TENIS) definition is becoming more clinically relevant as alternative treatment methods are available. This study examined the correlation between Tg levels with I-131 uptake in remnant thyroid gland to evaluate the reliability of serum Tg levels in predicting I-131 uptake. METHODS: From March 2012 to July 2019, 281 papillary thyroid cancer patients treated with 150 mCi RAI were retrospectively enrolled. Early (2nd day) and Delayed (7th day) post-RAI whole-body scan (WBS) neck counts were correlated with clinical and pathologic findings. Patients with normal neck ultrasound and undetectable level of serum Tg (< 0.2 ng/mL) and thyroglobulin antibody (TgAb) (< 10 IU/mL) were defined as ablation success within 2 years after I-131 ablation. RESULTS: Thyroid gland weight, tumor size and thyroiditis were independent factors of preoperative serum Tg levels. Serum off-Tg levels correlated with Early and Delayed WBS neck counts, and thyroiditis pathology contributed to lower neck counts in both Early and Delayed WBSs. In multivariable analysis, Delayed WBS neck count, serum off-Tg and off-TgAb were significant factors for predicting ablation success. CONCLUSION: I-131 uptake and retention in remnant thyroid gland correlates with serum off-Tg levels, thyroiditis, and ablation success in thyroid cancer patients receiving high-dose I-131 therapy. Semi-quantitative I-131 analysis with Early and Delayed WBSs provides additional information in evaluating ablation success, with the potential application for metastasis treatment response evaluation.

Significant Impact of Coffee Consumption on MR-Based Measures of Cardiac Function in a Population-Based Cohort Study without Manifest Cardiovascular Disease.

Subclinical effects of coffee consumption (CC) with regard to metabolic, cardiac, and neurological complications were evaluated using a whole-body magnetic resonance imaging (MRI) protocol. A blended approach was used to estimate habitual CC in a population-based study cohort without a history of cardiovascular disease. Associations of CC with MRI markers of gray matter volume, white matter hyperintensities, cerebral microhemorrhages, total and visceral adipose tissue (VAT), hepatic proton density fat fraction, early/late diastolic filling rate, end-diastolic/-systolic and stroke volume, ejection fraction, peak ejection rate, and myocardial mass were evaluated by linear regression. In our analysis with 132 women and 168 men, CC was positively associated with MR-based cardiac function parameters including late diastolic filling rate, stroke volume (p < 0.01 each), and ejection fraction (p < 0.05) when adjusting for age, sex, smoking, hypertension, diabetes, Low-density lipoprotein (LDL), triglycerides, cholesterol, and alcohol consumption. CC was inversely associated with VAT independent of demographic variables and cardiovascular risk factors (p < 0.05), but this association did not remain significant after additional adjustment for alcohol consumption. CC was not significantly associated with potential neurodegeneration. We found a significant positive and independent association between CC and MRI-based systolic and diastolic cardiac function. CC was also inversely associated with VAT but not independent of alcohol consumption.

Diagnostic Yield of Body CT and Whole-Body FDG PET/CT for Initial Systemic Staging in Patients With Suspected Primary CNS Lymphoma: A Systematic Review and Meta-Analysis.

BACKGROUND. Several guidelines recommend body imaging for the initial work-up of patients with suspected primary CNS lymphoma, to exclude subclinical systemic involvement. However, to our knowledge, the diagnostic yield of body CT (contrast-enhanced CT of the chest, abdomen, and pelvis) and whole-body FDG PET/CT for the evaluation of subclinical systemic lymphoma has not yet been systematically evaluated. OBJECTIVE. The purpose of this study was to investigate and compare the diagnostic yield of body CT and whole-body FDG PET/CT in detecting subclinical systemic lymphoma in patients with suspected primary CNS lymphoma. EVIDENCE ACQUISITION. A systematic search of the MEDLINE and EMBASE databases through July 5, 2020, was conducted to identify studies evaluating the diagnostic yield of body CT or whole-body FDG PET/CT in detecting subclinical systemic lymphoma in patients with suspected primary CNS lymphoma. Pooled estimates of the diagnostic yield of both imaging modalities were calculated using the DerSimonian and Laird random-effects model. The false referral rate and the rate of incidental secondary malignancy were also pooled. EVIDENCE SYNTHESIS. Nine original articles on studies evaluating a total of 1040 patients were included. In detecting subclinical systemic lymphoma, the pooled diagnostic yields of body CT and whole-body FDG PET/CT were 2.5% (95% CI, 1.5-3.9%) and 4.9% (95% CI, 2.8-8.5%), respectively. In the subgroup analysis, the diagnostic yield of whole-body FDG PET/CT was significantly higher than that of body CT (p = .03). Four studies reported changes in the management plan: the R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) regimen with or without radiation therapy was added if extracranial lymphoma involvement was detected by body CT or whole-body FDG PET/CT. The pooled false referral rate of whole-body FDG PET/CT was 5.3% (95% CI, 2.2-12.0%). The pooled rate of incidental secondary malignancy detected on whole-body FDG PET/CT was 3.1% (95% CI, 1.7-5.6%). CONCLUSION. Body imaging should be used in the initial workup of patients with suspected primary CNS lymphoma, to exclude systemic involvement. Whole-body FDG PET/CT may be a better alternative to body CT. CLINICAL IMPACT. Our results support current National Comprehensive Cancer Network guidelines for the use of body imaging to exclude subclinical systemic involvement in patients with suspected primary CNS lymphoma.

Whole-Body Imaging of Multiple Myeloma: Diagnostic Criteria.

Multiple myeloma (MM) is a clonal plasma cell proliferative disorder characterized by primary infiltration of bone marrow and excessive production of abnormal immunoglobulin. This disease is the second most common hematologic malignancy (after lymphoma), and its spectrum of characteristic features are widely known by the acronym CRAB (hypercalcemia, renal impairment, anemia, and bone lesions). Traditionally, the diagnosis and treatment of MM have been triggered by clear end-organ damage. However, owing to recently introduced treatment options that can extend patient survival and the increasing recognition of biomarkers that can be used to identify patients at high risk of progression to active disease, the diagnostic criteria have been revised. Bone disease is one of the most prominent features of MM, and imaging has an important role in diagnosis and follow-up, with each whole-body imaging modality having different indications in distinct disease situations. Skeletal survey has been the standard imaging procedure used during the past decade, but it should no longer be used unless it is the only option. Whole-body low-dose CT is a reasonable and cost-effective initial imaging approach. Whole-body MRI is the most sensitive technique for detecting bone involvement and assessing painful complications. PET/CT is the best tool for evaluating treatment response. The importance of radiologists has increased in this scenario. Therefore, to properly assist hematologists and improve the care of patients with MM, it is essential that radiologists know the updated diagnostic criteria for MM, indications for and limitations of each imaging option, and recommendations for follow-up. Online supplemental material is available for this article. ©RSNA, 2019.

Clinical outcomes of patients with T4 or N1b well-differentiated thyroid cancer after different strategies of adjuvant radioiodine therapy.

We aimed to determine whether recombinant human thyrotropin (rhTSH) plus 3.7 GBq could replace thyroid hormone withdrawal (THW) plus 5.55 GBq for adjuvant radioactive iodine (RAI) therapy in differentiated thyroid cancer (DTC) patients with T4 or N1b disease. This study was a retrospective study comparing ablation success rate, response to initial therapy, and recurrence-free survival (RFS) of patients with rhTSH plus 3.7 GBq versus those with THW plus 5.55 GBq in 253 DTC patients with T4 or N1b disease. There were no differences in the TSH-stimulated thyroglobulin level, rate of incomplete response after initial treatment, or the RFS between the two treatment strategies. However, thyroid bed uptake on follow-up diagnostic RAI whole-body scanning (WBS) was more frequently observed in the group treated with rhTSH plus 3.7 GBq than in the group with THW plus 5.55 GBq. Adjuvant RAI therapy with rhTSH plus 3.7 GBq had comparable results in the absence of persistent tumor, compared with that with THW plus 5.55 GBq. Although thyroid bed uptake was more frequently observed, rhTSH plus 3.7 GBq may be used instead of THW plus 5.55 GBq for adjuvant RAI therapy in patients with T4 or N1b disease.

Preclinical Study of Biofunctional Polymer-Coated Upconversion Nanoparticles.

Upconversion nanoparticles (UCNPs) are new-generation photoluminescent nanomaterials gaining considerable recognition in the life sciences due to their unique optical properties that allow high-contrast imaging in cells and tissues. Upconversion nanoparticle applications in optical diagnosis, bioassays, therapeutics, photodynamic therapy, drug delivery, and light-controlled release of drugs are promising, demanding a comprehensive systematic study of their pharmacological properties. We report on production of biofunctional UCNP-based nanocomplexes suitable for optical microscopy and imaging of HER2-positive cells and tumors, as well as on the comprehensive evaluation of their pharmacokinetics, pharmacodynamics, and toxicological properties using cells and laboratory animals. The nanocomplexes represent a UCNP core/shell structure of the NaYF4:Yb, Er, Tm/NaYF4 composition coated with an amphiphilic alternating copolymer of maleic anhydride with 1-octadecene (PMAO) and conjugated to the Designed Ankyrin Repeat Protein (DARPin 9_29) with high affinity to the HER2 receptor. We demonstrated the specific binding of UCNP-PMAO-DARPin to HER2-positive cancer cells in cultures and xenograft animal models allowing the tumor visualization for at least 24 h. An exhaustive study of the general and specific toxicity of UCNP-PMAO-DARPin including the evaluation of their allergenic, immunotoxic, and reprotoxic properties was carried out. The obtained experimental body of evidence leads to a conclusion that UCNP-PMAO and UCNP-PMAO-DARPin are functional, noncytotoxic, biocompatible, and safe for imaging applications in cells, small animals, and prospective clinical applications of image-guided surgery.

Panoptic imaging of transparent mice reveals whole-body neuronal projections and skull-meninges connections.

Analysis of entire transparent rodent bodies after clearing could provide holistic biological information in health and disease, but reliable imaging and quantification of fluorescent protein signals deep inside the tissues has remained a challenge. Here, we developed vDISCO, a pressure-driven, nanobody-based whole-body immunolabeling technology to enhance the signal of fluorescent proteins by up to two orders of magnitude. This allowed us to image and quantify subcellular details through bones, skin and highly autofluorescent tissues of intact transparent mice. For the first time, we visualized whole-body neuronal projections in adult mice. We assessed CNS trauma effects in the whole body and found degeneration of peripheral nerve terminals in the torso. Furthermore, vDISCO revealed short vascular connections between skull marrow and brain meninges, which were filled with immune cells upon stroke. Thus, our new approach enables unbiased comprehensive studies of the interactions between the nervous system and the rest of the body.

Predicting 131I-avidity of metastases from differentiated thyroid cancer using 18F-FDG PET/CT in postoperative patients with elevated thyroglobulin.

The quantitative relationship between iodine and glucose metabolism in metastases from differentiated thyroid cancer (DTC) remains unknown. Aim of the prospective study was to establish the value of 18F-FDG PET/CT in predicting 131I-avidity of metastases from DTC before the first radioiodine therapy. A total of 121 postoperative DTC patients with elevated stimulated serum thyroglobulin (ssTg) who underwent 131I adjuvant therapy or therapy after 18F-FDG PET/CT scan were enrolled. The Receiver operating characteristic curve was established to create an optimal cut-off point and evaluate the value of SUVmax for predicting 131I-avidity. In our study, the median SUVmax in 131I-nonavid metastatic target lesions was also significantly higher than that in 131I-avid metastatic target lesions (5.37 vs. 3.30; P = 0.000). At a cut-off value of 4.0 in SUVmax, the area under curve was 0.62 with the sensitivity, specificity, positive predictive value and negative predictive value of 75.3%, 56.7%, 76.1%, and 54.8%, respectively. These results suggest that 18F-FDG PET/CT may be of great value in identifying metastases in postoperative DTC patients with elevated ssTg before 131I administration, leading to an improved management of disease. 18F-FDG positive metastatic DTC with SUVmax of greater than 4.0 possesses higher probability of non-avidity to radioiodine.

Reduction of 18F-FDG Dose in Clinical PET/MR Imaging by Using Silicon Photomultiplier Detectors.

Purpose To determine the level of clinically acceptable reduction in injected fluorine 18 (18F) fluorodeoxyglucose (FDG) dose in time-of-flight (TOF)-positron emission tomography(PET)/magnetic resonance (MR) imaging by using silicon photomultiplier (SiPM) detectors compared with TOF-PET/computed tomography (CT) using Lu1.8Y0.2SiO5(Ce), or LYSO, detectors in patients with different body mass indexes (BMIs). Materials and Methods Patients were enrolled in this study as part of a larger prospective study with a different purpose than evaluated in this study (NCT02316431). All patients gave written informed consent prior to inclusion into the study. In this study, 74 patients with different malignant diseases underwent sequential whole-body TOF-PET/CT and TOF-PET/MR imaging. PET images with simulated reduction of injected 18F-FDG doses were generated by unlisting the list-mode data from PET/MR imaging. Two readers rated the image quality of whole-body data sets, as well as the image quality in each body compartment, and evaluated the conspicuity of malignant lesions. Results The image quality with 70% or 60% of the injected dose of 18F-FDG at PET/MR imaging was comparable to that at PET/CT. With 50% of the injected dose, comparable image quality was maintained among patients with a BMI of less than 25 kg/m2. PET images without TOF reconstruction showed higher artifact scores and deteriorated sharpness than those with TOF reconstruction. Conclusion Sixty percent of the usually injected 18F-FDG dose (reduction of up to 40%) in patients with a BMI of more than 25 kg/m2 results in clinically adequate PET image quality in TOF-PET/MR imaging performed by using SiPM detectors. Additionally, in patients with a BMI of less than 25 kg/m2, 50% of the injected dose may safely be used. © RSNA, 2017 Online supplemental material is available for this article.

Whole-Body Profiling of Cancer Metastasis with Single-Cell Resolution.

Stochastic and proliferative events initiated from a single cell can disrupt homeostatic balance and lead to fatal disease processes such as cancer metastasis. To overcome metastasis, it is necessary to detect and quantify sparsely distributed metastatic cells throughout the body at early stages. Here, we demonstrate that clear, unobstructed brain/body imaging cocktails and computational analysis (CUBIC)-based cancer (CUBIC-cancer) analysis with a refractive index (RI)-optimized protocol enables comprehensive cancer cell profiling of the whole body and organs. We applied CUBIC-cancer analysis to 13 mouse models using nine cancer cell lines and spatiotemporal quantification of metastatic cancer progression at single-cell resolution. CUBIC-cancer analysis suggests that the epithelial-mesenchymal transition promotes not only extravasation but also cell survival at metastatic sites. CUBIC-cancer analysis is also applicable to pharmacotherapeutic profiling of anti-tumor drugs. CUBIC-cancer analysis is compatible with in vivo bioluminescence imaging and 2D histology. We suggest that a scalable analytical pipeline with these three modalities may contribute to addressing currently incurable metastatic diseases.

A concept for holistic whole body MRI data analysis, Imiomics.

PURPOSE: To present and evaluate a whole-body image analysis concept, Imiomics (imaging-omics) and an image registration method that enables Imiomics analyses by deforming all image data to a common coordinate system, so that the information in each voxel can be compared between persons or within a person over time and integrated with non-imaging data. METHODS: The presented image registration method utilizes relative elasticity constraints of different tissue obtained from whole-body water-fat MRI. The registration method is evaluated by inverse consistency and Dice coefficients and the Imiomics concept is evaluated by example analyses of importance for metabolic research using non-imaging parameters where we know what to expect. The example analyses include whole body imaging atlas creation, anomaly detection, and cross-sectional and longitudinal analysis. RESULTS: The image registration method evaluation on 128 subjects shows low inverse consistency errors and high Dice coefficients. Also, the statistical atlas with fat content intensity values shows low standard deviation values, indicating successful deformations to the common coordinate system. The example analyses show expected associations and correlations which agree with explicit measurements, and thereby illustrate the usefulness of the proposed Imiomics concept. CONCLUSIONS: The registration method is well-suited for Imiomics analyses, which enable analyses of relationships to non-imaging data, e.g. clinical data, in new types of holistic targeted and untargeted big-data analysis.

Preclinical acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of [(18)F]fluorocholine in mice.

[(18)F]Fluorocholine ([(18)F]FCH) has been proven to be effective in prostate cancer. Since [(18)F]FCH is classified as a new radiopharmaceutical in Brazil, preclinical safety and efficacy data are required to support clinical trials and to obtain its approval. The aim of this work was to perform acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of [(18)F]FCH. The results could support its use in nuclear medicine as an important piece of work for regulatory in Brazil.

Comparable Ablation Efficiency of 30 and 100 mCi of I-131 for Low to Intermediate Risk Thyroid Cancers Using Triple Negative Criteria.

BACKGROUND: There is controversy about ablation efficacy of low or high doses of radioiodine-131 (RAI) in patients with differentiated thyroid cancers (DTC). The purpose of this prospective study was to determine efficacy of 30 mCi and 100 mCi of RAI to achieve successful ablation in patients with low to intermediate risk DTC. MATERIALS AND METHODS: This prospective cross sectional study was conducted from April 2013 to November 2015. Inclusion criteria were patients of either gender, 18 years or older, having low to intermediate risk papillary and follicular thyroid cancers with T1-3, N0/N1/Nx but no evidence of distant metastasis.Thirty-nine patients were administered 30 mCi of RAI while 61 patients were given 100 mCi. Informed consent was acquired from all patients and counseling was done by nuclear physicians regarding benefits and possible side effects of RAI. After an average of 6 months (range 6-16 months; 2-3 weeks after thyroxin withdrawal), these patients were followed up for stimulated TSH, thyroglobulin (sTg) and thyroglobulin antibodies, ultrasound neck (U/S) and a diagnostic whole body iodine scan (WBIS) for ablation outcome. Successful ablation was concluded with stimulated Tg< 2ng/ml with negative antibodies, negative U/S and a negative diagnostic WBIS (triple negative criteria). ROC curve analysis was used to find diagnostic strength of baseline sTg to predict successful ablation. RESULTS: Successful ablation based upon triple negative criteria was 56% in the low dose and 57% in the high dose group (non-significant difference). Based on a single criterion (follow-up sTg<2 ng/ml), values were 82% and 77% (again non-significant). The ROC curve revealed that a baseline sTg level ≤ 7.4 ng/ml had the highest diagnostic strength to predict successful ablation in all patients. CONCLUSIONS: We conclude that 30 mCi of RAI has similar ablation success to 100 mCi dose in patients with low to intermediate risk DTC. A baseline sTg ≤ 7.4 ng/ml is a strong predictor of successful ablation in all patients. Low dose RAI is safer, more cost effective and more convenient for patients and healthcare providers.

Antenatal and postnatal radiologic diagnosis of holocarboxylase synthetase deficiency: a systematic review.

BACKGROUND: Holocarboxylase synthetase deficiency results in impaired activation of enzymes implicated in glucose, fatty acid and amino acid metabolism. Antenatal imaging and postnatal imaging are useful in making the diagnosis. Untreated holocarboxylase synthetase deficiency is fatal, while antenatal and postnatal biotin supplementation is associated with good clinical outcomes. Although biochemical assays are required for definitive diagnosis, certain radiologic features assist in the diagnosis of holocarboxylase synthetase deficiency. OBJECTIVE: To review evidence regarding radiologic diagnostic features of holocarboxylase synthetase deficiency in the antenatal and postnatal period. MATERIALS AND METHODS: A systematic review of all published cases of holocarboxylase synthetase deficiency identified by a search of Pubmed, Scopus and Web of Science. RESULTS: A total of 75 patients with holocarboxylase synthetase deficiency were identified from the systematic review, which screened 687 manuscripts. Most patients with imaging (19/22, 86%) had abnormal findings, the most common being subependymal cysts, ventriculomegaly and intraventricular hemorrhage. CONCLUSION: Although the radiologic features of subependymal cysts, ventriculomegaly, intraventricular hemorrhage and intrauterine growth restriction may be found in the setting of other pathologies, these findings should prompt consideration of holocarboxylase synthetase deficiency in at-risk children.

Core-Shell MnSe@Bi2 Se3 Fabricated via a Cation Exchange Method as Novel Nanotheranostics for Multimodal Imaging and Synergistic Thermoradiotherapy.

MnSe@Bi2 Se3 core-shell nanostructures with highly integrated imaging and therapy functions are fabricated by a simple cation exchange method. Using those nanoparticles as a theranostic agent, a promise concept is further demonstrated to enhance conventional radiotherapy by: i) using X-ray absorbing agents to locally concentrate radiation energy and ii) employing near-infrared-light-triggered photothermal therapy to overcome hypoxia-associated radioresistance.

Seeing the forest and trees: whole-body and whole-brain imaging for circadian biology.

Recent advances in methods for making mammalian organs translucent have made possible whole-body fluorescent imaging with single-cell resolution. Because organ-clearing methods can be used to image the heterogeneous nature of cell populations, they are powerful tools to investigate the hierarchical organization of the cellular circadian clock, and how the clock synchronizes a variety of physiological activities. In particular, methods compatible with genetically encoded fluorescent reporters have the potential to detect circadian activity in different brain regions and the circadian-phase distribution across the whole body. In this review, we summarize the current methods and strategy for making organs translucent (removal of lipids, decolourization of haemoglobin and adjusting the refractive index of the specimen). We then discuss possible applications to circadian biology. For example, the coupling of circadian rhythms among different brain regions, brain activity in sleep-wake cycles and the role of migrating cells such as immune cells and cancer cells in chronopharmacology.

Clinical application of ultrasound for preparation of (99m)Tc-sestamibi complex.

OBJECTIVE: The main aim of this investigation is the clinical application of ultrasound irradiation technique as an alternative method to reconstitute sestamibi kits in comparison of water boiling bath method. METHODS: The 740-3700 MBq (20-100 mCi) (99m)Tc-MIBI (sestamibi) complex samples were prepared due to ultrasound irradiation technique or boiled water bath method as a standard method. Twenty patients (8 men and 12 women; age range 30-72, median 52.45 years) have been referred to Golestan hospital for myocardial perfusion imaging (MPI). The subjects have been divided randomly into group A (3 men, 7 women, age range 36-67, median 51.7 years) and group B (5 men, 5 women, age range 30-72, median 50.3 years), respectively. The (99m)Tc-MIBI radiopharmaceuticals have been prepared by Ultrasound irradiation technique administrated to group A and (99m)Tc-MIBI complex samples due to the boiled water bath technique administrated to the other group. For all patients, the 2-day stress/rest MPI protocol was performed. RESULTS: The radio-HPLC and TLC studies have indicated that the (99m)Tc-MIBI complex samples with good yields could be prepared successfully due to new developed technique. The scintigraphy imaging studies have demonstrated that the (99m)Tc-sestamibi prepared due to the above-mentioned modalities shows very identical biodistribution in the heart, thyroid, lung, liver, gallbladder, kidneys, stomach, large intestine and bladder of the subjects. Any unexpected accumulation of radiotracer samples have not been observed in our approach. CONCLUSIONS: The ultrasound irradiation technique is convenient and sufficient method to prepare (99m)Tc-sestamibi. It can be recommended as an alternative method to reconstitute sestamibi kits particularly in emergency situations to reduce potentially medical risk by avoiding any delay in acute therapy for myocardial infarction.

Expressive body movement responses to music are coherent, consistent, and low dimensional.

Embodied music cognition stresses the role of the human body as mediator for the encoding and decoding of musical expression. In this paper, we set up a low dimensional functional model that accounts for 70% of the variability in the expressive body movement responses to music. With the functional principal component analysis, we modeled individual body movements as a linear combination of a group average and a number of eigenfunctions. The group average and the eigenfunctions are common to all subjects and make up what we call the commonalities. An individual performance is then characterized by a set of scores (the individualities), one score per eigenfunction. The model is based on experimental data which finds high levels of coherence/consistency between participants when grouped according to musical education. This shows an ontogenetic effect. Participants without formal musical education focus on the torso for the expression of basic musical structure (tempo). Musically trained participants decode additional structural elements in the music and focus on body parts having more degrees of freedom (such as the hands). Our results confirm earlier studies that different body parts move differently along with the music.

A case of post-mogamulizumab relapse of acute-type adult T-cell leukemia/lymphoma successfully treated with mogamulizumab and etoposide.

A 70-year-old man presented to us with the chief complaints of a generalized rash and a mass in the right clavicular region that he first noticed in the year 2012. Biopsy of the mass led to the diagnosis of cutaneous nodular mass-type adult T-cell leukemia/lymphoma (ATLL) in March 2013. Phototherapy was started, and the symptoms improved temporarily. However, in late June 2013, the serum lactate dehydrogenase (LDH) level increased to 358 IU/L, which was 1.6 times higher than the upper limit of the reference range; based on the findings, transformation of the disease to the acute type was diagnosed. The patient was treated with 6 courses of CHOP therapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone), which resulted in complete remission (CR). However, the rash recurred in late October 2013, and treatment with mogamulizumab was initiated. A total of 8 courses of mogamulizumab were administered, which resulted in CR. The rash and cutaneous nodular masses recurred again in January 2014, and a total of 8 courses of mogamulizumab were administered again starting in February 2014. However, the patient's symptoms began to worsen gradually. Phototherapy was also initiated, but had to be discontinued due to the development of photosensitivity. Treatment with the combination of mogamulizumab and etoposide (25 mg/day for 21 days) was started in May 2014. The nodular mass rapidly decreased in size. The rash or cutaneous nodular mass had not recurred as of August 2014. Thus, combined therapy with mogamulizumab plus etoposide is considered to be effective for resolution of the cutaneous nodular masses in patients with ATLL.

Iodinated oil-loaded, fluorescent mesoporous silica-coated iron oxide nanoparticles for magnetic resonance imaging/computed tomography/fluorescence trimodal imaging.

In this study, a novel magnetic resonance imaging (MRI)/computed tomography (CT)/fluorescence trifunctional probe was prepared by loading iodinated oil into fluorescent mesoporous silica-coated superparamagnetic iron oxide nanoparticles (i-fmSiO4@SPIONs). Fluorescent mesoporous silica-coated superparamagnetic iron oxide nanoparticles (fmSiO4@SPIONs) were prepared by growing fluorescent dye-doped silica onto superparamagnetic iron oxide nanoparticles (SPIONs) directed by a cetyltrimethylammonium bromide template. As prepared, fmSiO4@SPIONs had a uniform size, a large surface area, and a large pore volume, which demonstrated high efficiency for iodinated oil loading. Iodinated oil loading did not change the sizes of fmSiO4@SPIONs, but they reduced the MRI T2 relaxivity (r2) markedly. I-fmSiO4@SPIONs were stable in their physical condition and did not demonstrate cytotoxic effects under the conditions investigated. In vitro studies indicated that the contrast enhancement of MRI and CT, and the fluorescence signal intensity of i-fmSiO4@SPION aqueous suspensions and macrophages, were intensified with increased i-fmSiO4@SPION concentrations in suspension and cell culture media. Moreover, for the in vivo study, the accumulation of i-fmSiO4@SPIONs in the liver could also be detected by MRI, CT, and fluorescence imaging. Our study demonstrated that i-fmSiO4@SPIONs had great potential for MRI/CT/fluorescence trimodal imaging.