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.

Physeal Abnormalities in Children With High-risk Neuroblastoma Intensively Treated With/Without 13-Cis-Retinoic Acid.

BACKGROUND: This study aimed to investigate the presence of physeal abnormality and its effect on growth in children with high-risk neuroblastoma treated by intensive multimodal treatment with/without 13-cis-retinoic acid (13-CRA). METHODS: Fifteen patients diagnosed with high-risk neuroblastomas at the age of 1 to 10 years, who received treatment such as high-dose chemotherapy and autologous stem cell transplantation with/without 13-CRA, and with complete data during their >2-year follow-up were retrospectively reviewed. The physeal abnormalities were investigated by whole-body magnetic resonance imaging, serially performed every 3 to 6 months. The patients' height growth was also investigated and compared with that of age-and-sex-matched patients with brain tumors who also underwent high-dose chemotherapy and autologous stem cell transplantation. RESULTS: Six of 15 patients presented multifocal physeal abnormalities during follow-up, and all lesions occurred in patients with 13-CRA use. The lesions in 3 patients completely resolved spontaneously without any adverse effect on growth, but some lesions in the other 3 patients progressed to disturb the bony growth. Height growth of matched patients with brain tumors were not significantly different, and none of the matched controls showed definite bony deformity during the follow-up. CONCLUSIONS: Some children who were treated for high-risk neuroblastomas experienced multifocal physeal insults, probably due to the use of 13-CRA. Most lesions resolved spontaneously, but some led to bony deformity. If the lesions are not followed by premature physeal closure, there seems to be no further adverse effect of 13-CRA on leg length growth. Routine periodic screening for physeal status is needed for the patients with high-risk neuroblastomas using 13-CRA. LEVEL OF EVIDENCE: Level IV-prognostic study.

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.

Posttraumatic Scab on 131I Whole-Body Scan-A False-Positive Finding.

ABSTRACT: 131I scan plays a crucial role in the management of patients with differentiated thyroid cancer for the evaluation of remnant thyroid tissue, residual/recurrent metastatic disease, posttherapy tracer distribution, and response assessment to high-dose 131I therapy. Different causes secondary to physiological, pathological, and anatomical variations have been described for false-positive findings in the whole-body planar images. This case report of a patient of differentiated thyroid cancer with undocumented trauma to the left knee region a day before receiving the high-dose radioiodine therapy showed an interesting image finding of tracer uptake at unusual site in the posttherapy whole-body 131I scan.

The relationship between the quantitative evaluation of thyroid bed uptake and the disappearance of accumulation in adjuvant radioactive iodine therapy for differentiated thyroid cancer.

OBJECTIVE: Iodine-131 (I-131) radioactive iodine therapy (RAI) after total thyroidectomy is the standard treatment for patients with differentiated thyroid cancer (DTC). We investigated the relationship between the quantitative parameters of the iodine uptake and the disappearance of the accumulation in the thyroid bed in adjuvant therapy using a 1.11 GBq or 3.70 GBq dose of I-131. METHODS: We retrospectively analyzed the cases of 40 patients with DTC who were treated with RAI at our institution between April 2017 and August 2019. The patients were treated with the I-131 dose of 1.11 GBq (n = 25) or 3.70 GBq (n = 15) after total thyroidectomy. The I-131 whole-body scan and hybrid single-photon emission computed tomography/X-ray computed tomography (SPECT/CT) were performed 3 days after RAI. Using image analysis software, we measured the standardized uptake value (SUV) and absolute radioactivity concentration (kBq/ml) on the target lesions with the highest uptake in the thyroid bed. RESULTS: The median period from RAI to the evaluation of the absence of uptake of the thyroid bed was 6.75 months. After RAI, uptake of the thyroid bed disappeared in 26 of the 40 patients. The disappearance rate was significantly higher in the 3.70 GBq group than in the 1.11 GBq group (86.7% vs. 52.0%, respectively; p = 0.029). However, there were no significant differences in the values of kBq/ml or SUV between the 1.11 GBq group and 3.70 GBq group. On the other hand, the group in which the uptake disappeared after RAI showed significantly higher kBq/ml max and kBq/ml mean values than the group in which the uptake did not disappear after RAI (p = 0.028, p = 0.032, respectively). The SUVmax and SUVmean also tended to be higher in the disappeared-uptake group than the not-disappeared-uptake group, but the differences were not significant (p = 0.166, p = 0.176, respectively). CONCLUSIONS: The quantitative evaluation might be useful as one of the predictive indicators of the disappearance of the accumulation of radioactive iodine in the thyroid bed.

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.

68Ga-DOTATATE and 123I-mIBG as imaging biomarkers of disease localisation in metastatic neuroblastoma: implications for molecular radiotherapy.

PURPOSE: Iodine-131-labelled meta-iodobenzylguanidine (I-mIBG) and lutetium-177-labelled DOTATATE (Lu-DOTATATE) are used for molecular radiotherapy of metastatic neuroblastoma. These are taken up by the noradrenaline transporter (NAT) and the somatostatin receptor subtype 2 (SSTR-2), respectively. Scintigraphy of iodine-123-labelled meta-iodobenzylguanidine (I-mIBG) and gallium-68 DOTATATE (Ga-DOTATATE) PET are used to select patients for therapy. These demonstrate the extent and location of tumour, and avidity of uptake by cells expressing NAT and SSTR-2, respectively. This study compared the similarities and differences in the anatomical distribution of these two imaging biomarkers in an unselected series of patients with metastatic neuroblastoma undergoing assessment for molecular radiotherapy. METHODS: Paired whole-body planar I-mIBG views and Ga-DOTATATE maximum intensity projection PET scans of metastatic neuroblastoma patients were visually compared. The disease extent was assessed by a semiquantitative scoring method. RESULTS: Paired scans from 42 patients were reviewed. Ga-DOTATATE scans were positive in all patients, I-mIBG scans were negative in two. In two patients, there was a mismatch, with some lesions identified only on the I-mIBG scan, and others visible only on the Ga-DOTATATE scan. CONCLUSION: Ga-DOTATATE and I-mIBG scans yield complementary information. For a more comprehensive assessment, consideration could be given to the use of both I-mIBG and Ga-DOTATATE imaging scans. Because of the heterogeneity of distribution of molecular targets revealed by these techniques, a combination of both I-mIBG and Lu-DOTATATE molecular radiotherapy may possibly be more effective than either alone.

Bismuth chelate as a contrast agent for X-ray computed tomography.

BACKGROUNDS: Due to the unexpected side effects of the iodinated contrast agents, novel contrast agents for X-ray computed tomography (CT) imaging are urgently needed. Nanoparticles made by heavy metal elements are often employed, such as gold and bismuth. These nanoparticles have the advantages of long in vivo circulation time and tumor targeted ability. However, due to the long residence time in vivo, these nanoparticles may bring unexpected toxicity and, the preparation methods of these nanoparticles are complicated and time-consuming. METHODS: In this investigation, a small molecular bismuth chelate using diethylenetriaminepentaacetic acid (DPTA) as the chelating agent was proposed to be an ideal CT contrast agent. RESULTS: The preparation method is easy and cost-effective. Moreover, the bismuth agent show better CT imaging for kidney than iohexol in the aspect of improved CT values. Up to 500 µM, the bismuth agent show negligible toxicity to L02 cells and negligible hemolysis. And, the bismuth agent did not induce detectable morphology changes to the main organs of the mice after intravenously repeated administration at a high dose of 250 mg/kg. The pharmacokinetics of the bismuth agent follows the first-order elimination kinetics and, it has a short half-life time of 0.602 h. The rapid clearance from the body promised its excellent biocompatibility. CONCLUSIONS: This bismuth agent may serve as a potential candidate for developing novel contrast agent for CT imaging in clinical applications.

Randomised comparison of 1.1 GBq and 3.7 GBq radioiodine to ablate the thyroid in the treatment of low-risk thyroid cancer: a 13-year follow-up.

Purpose: The optimal activity of radioiodine (I-131) administered for ablation therapy in papillary and follicular thyroid cancer after thyroidectomy remains unknown in a long-term (> 10 year) follow-up. Some, shorter follow-up studies suggest that activities 1.1 GBq and 3.7 GBq are equally effective. We evaluated the long-term outcomes after radioiodine treatment to extend current knowledge about the optimal ablative dose of I-131.Methods: One hundred and sixty consecutive adult patients (129 females, 31 males; mean age 46 ± 14 y, range 18-89 y) diagnosed with histologically confirmed differentiated thyroid cancer, were randomised in a prospective, phase III, open-label, single-centre study, to receive either 1.1 GBq or 3.7 GBq of I-131 after thyroidectomy. At randomisation, patients were stratified according to the histologically verified cervical lymph node status and were prepared for ablation using thyroid hormone withdrawal. No uptake in the whole-body scan with I-131 and serum thyroglobulin concentration less than 1 ng/mL at 4-8 months after treatment was considered successful ablation.Results: Median follow-up time was 13.0 years (mean 11.0 ± 4.8 y; range 0.3-17.1 y). Altogether 81 patients received 1.1 GBq with successful ablation in 45 (56%) patients. In the original study, thirty-six patients (44%) needed one or more extra administrations to replete the ablation. Of these, 4 (8.9%) and 5 (14%) patients relapsed during the follow-up, respectively. Of the 79 patients treated with 3.7 GBq 45 (57%) had successful ablation after one administration of radioiodine and 34 (43%) needed several treatments. Of these, 2 (4.4%) and 9 (26.5%) patients relapsed, respectively. The groups did not differ in the proportion of patients relapsing (p = .591).Conclusion: During follow-up of median 13 years, 3.7 GBq is not superior to 1.1 GBq in the radioiodine treatment after thyroidectomy in papillary and follicular thyroid cancer.

Unexpected radioactive iodine accumulation on whole-body scan after I-131 ablation therapy for differentiated thyroid cancer.

We retrospectively evaluated the frequency of unexpected accumulation of radioactive iodine on the post-therapy whole-body scan (Rx-WBS) after radioactive iodine (RAI) ablation therapy in patients with differentiated thyroid cancer (DTC). We searched our institutional database for Rx-WBSs of DTC patients who underwent RAI ablation or adjuvant therapy between 2012 and 2019. Patients with distant metastasis diagnosed by CT or PET/CT before therapy, and those had previously received RAI therapy were excluded. In total, 293 patients (201 female and 92 male, median age 54 years) were selected. Two nuclear medicine physicians interpreted the Rx-WBS images by determining the visual intensity of radioiodine uptake by the thyroid bed, cervical and mediastinal lymph nodes, lungs, and bone. Clinical features of the patients with and without the metastatic accumulation were compared by chi-square test and median test. Logistic regression analyses were performed to compare the association between the presence of metastatic accumulation and these clinical factors. Eighty-four of 293 patients (28.7%) showed metastatic accumulation. Patients with metastatic RAI accumulation showed a significantly higher frequency of pathological N1 (pN1) and serum thyroglobulin (Tg) > 1.5 ng/ml under TSH stimulation (p = 0.035 and p = 0.031, respectively). Logistic regression analysis indicated that a serum Tg > 1.5 ng/ml was significantly correlated with the presence of metastatic accumulation (odds ratio = 1.985; p = 0.033). In conclusion, Patients with Tg > 1.5 ng/ml were more likely to show metastatic accumulation. In addition, the presence of lymph node metastasis at the initial thyroid surgery was also associated with this unexpected metastatic accumulation.

EDTA-Modified 17ß-Estradiol-Laden Upconversion Nanocomposite for Bone-Targeted Hormone Replacement Therapy for Osteoporosis.

Hormone therapy (HT) is one of the most effective treatments for osteoporosis. However, the nonselective accumulation of hormone in organs such as breast, heart and uterus other than bones causes serious side effects, which impedes the application of HT. Hence, it is critically important to develop a HT strategy with reduced non-specific enrichment of hormone drugs in non-target tissues and enhanced bone-targeting ability. Methods: Herein, a 17ß-estradiol (E2)-laden mesoporous silica-coated upconversion nanoparticle with a surface modification of ethylenediaminetetraacetic acid (EDTA) (NaLuF4:Yb,Tm@NaLuF4@mSiO2-EDTA-E2, E2-csUCNP@MSN-EDTA) is developed for bone-targeted osteoporosis hormone therapy. EDTA was attached onto the surface of E2 upconversion nanocomposite to enhance its affinity and efficiency targeting bone tissue and cells to optimize hormone replacement therapy for osteoporosis. We characterized the size, cytotoxicity, loading and release efficiency, in situ and ex vivo imaging. Further, in vitro and in vivo osteogenic ability was tested using preosteoblast and ovariectomy mouse model of osteoporosis. Results: The upconversion core of E2-csUCNP@MSN-EDTA nanoparticle serves as an excellent imaging agent for tracking the loaded hormone drug in vivo. The mesoporous silica layer has a high loading efficiency for E2 and provides a relatively long-lasting drug release within 50 h. EDTA anchored on the silica layer endows the nanocomposite with a bone targeting property. The nanocomposite effectively reverses estrogen deficiency-induced osteoporosis and reduces the damage of hormone to the uterus. The bone mineral density in the nanocomposite treatment group is nearly twice that of the ovariectomized (OVX) group. Compared with the E2 group, the uterine weight and luminal epithelial height were significantly lower in the nanocomposite treatment group. Conclusion: This work demonstrated that E2-csUCNP@MSN-EDTA alleviates the side effect of hormone therapy while maintaining its therapeutic efficacy, which has great potential for developing the next generation of methods for osteoporosis treatment.

Potential impacts of a novel integrated extracorporeal-CPR workflow using an interventional radiology and immediate whole-body computed tomography system in the emergency department.

Extracorporeal cardiopulmonary resuscitation (ECPR) can be associated with increased survival and neurologic benefits in selected patients with out-of-hospital cardiac arrest (OHCA). However, there remains insufficient evidence to recommend the routine use of ECPR for patients with OHCA. A novel integrated trauma workflow concept that utilizes a sliding computed tomography (CT) scanner and interventional radiology (IR) system, named a hybrid emergency room system (HERS), allowing emergency therapeutic interventions and CT examination without relocating trauma patients, has recently evolved in Japan. HERS can drastically shorten the ECPR implementation time and more quickly facilitate definitive interventions than the conventional advanced cardiovascular life support workflow. Herein, we discuss our novel workflow concept using HERS on ECPR for patients with OHCA.

Comparison of post-therapeutic sequential 131I whole-body scans in the detection of metastatic thyroid cancer.

BACKGROUND: The aim was to compare the detect ability of three sequential 131I whole-body scans (tri-WBS) on the second, third, and fourth day after 131I therapy for metastatic thyroid cancer. METHODS: Differentiated thyroid cancer patients who received oral high-dose 131I therapy underwent routinely tri-WBS on the second, third, and fourth day after total or near-total thyroidectomy in Zhongshan Hospital, Fudan University. We enrolled 137 patients with 261 tri-WBSs in this study between January 2015 and November 2017. The inclusion criteria was that at least one metastasis was found in the tri-WBS. We classified radioactive uptake of metastatic lesions by visual assessment into three grades: grade 0 = no uptake, grade 1= suspicious uptake, and grade 2 = definite uptake. The fourth day 131I WBS images were also compared with concurrent pre-therapeutic 99mTc-pertechnetate WBS images when available. We also analyzed the serum Tg levels of probably statistical difference in the patients with only lymph node, lung, bone, and multiple metastases when they underwent the first radioiodine ablation. RESULTS: A total of 722 metastatic accumulations were identified in the final decisions, including 293 lymph node metastases, 261 nodular pulmonary metastases, 49 diffuse bilateral pulmonary metastases, 106 bone metastases, and 13 other metastases. The differences of intensity of uptake in sequential three day images were significant in visualization of lymph node metastasis (χ2=124.432, P<0.001), nodular pulmonary metastasis (χ2=160.334, P<0.001), diffuse bilateral pulmonary metastasis (χ2=41.710, P<0.001), and bone metastasis (χ2=22.118, P<0.001) in our study. Compared to the second day scans, the fourth day scans detected 87 (29.70%) more metastatic lymph nodes, 111 (42.53%) more nodular pulmonary metastases, 26 (53.06%) more diffuse bilateral pulmonary metastases and 17 (16.95%) more bone metastases. The differences of intensity of uptake between 99mTc-pertechnetate WBS and the fourth day 131I WBS were significant in visualization of lymph node metastasis (χ2=172.624, P<0.001), nodular pulmonary metastasis (χ2=111.004, P<0.001), diffuse bilateral pulmonary metastasis (χ2=17.400, P<0.001) and bone metastasis (χ2=46.298, P<0.001). The means of RTg in the patients with only lymph node, lung, bone metastasis, and multiple metastases were 47.20, 76.58, 89.00, and 91.56, respectively. The differences of serum Tg levels in the patients with only lymph node, lung, bone metastasis, and multiple metastases were significant (χ2=35.850, P<0.001). CONCLUSIONS: The detect ability of tri-WBS was significantly different even for consecutive three-day images on the second, third, and fourth day after 131I therapy for metastatic thyroid cancer. There was a linear trend of increasing 131I uptake from the second to fourth day 131I WBS. The pre-therapy 99mTc-pertechnetate WBS demonstrated a poor ability to detect metastatic thyroid cancer compared to 131I WBS. There was an increasing trend of the means of RTg in patients with more extensive metastases.

Low SAR 31 P (multi-echo) spectroscopic imaging using an integrated whole-body transmit coil at 7T.

Phosphorus (31 P) MRSI provides opportunities to monitor potential biomarkers. However, current applications of 31 P MRS are generally restricted to relatively small volumes as small coils are used. Conventional surface coils require high energy adiabatic RF pulses to achieve flip angle homogeneity, leading to high specific absorption rates (SARs), and occupy space within the MRI bore. A birdcage coil behind the bore cover can potentially reduce the SAR constraints massively by use of conventional amplitude modulated pulses without sacrificing patient space. Here, we demonstrate that the integrated 31 P birdcage coil setup with a high power RF amplifier at 7 T allows for low flip angle excitations with short repetition time (TR ) for fast 3D chemical shift imaging (CSI) and 3D T1 -weighted CSI as well as high flip angle multi-refocusing pulses, enabling multi-echo CSI that can measure metabolite T2 , over a large field of view in the body. B1+ calibration showed a variation of only 30% in maximum B1 in four volunteers. High signal-to-noise ratio (SNR) MRSI was obtained in the gluteal muscle using two fast in vivo 3D spectroscopic imaging protocols, with low and high flip angles, and with multi-echo MRSI without exceeding SAR levels. In addition, full liver MRSI was achieved within SAR constraints. The integrated 31 P body coil allowed for fast spectroscopic imaging and successful implementation of the multi-echo method in the body at 7 T. Moreover, no additional enclosing hardware was needed for 31 P excitation, paving the way to include larger subjects and more space for receiver arrays. The increase in possible number of RF excitations per scan time, due to the improved B1+ homogeneity and low SAR, allows SNR to be exchanged for spatial resolution in CSI and/or T1 weighting by simply manipulating TR and/or flip angle to detect and quantify ratios from different molecular species.

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.

pH/redox dual-stimuli-responsive cross-linked polyphosphazene nanoparticles for multimodal imaging-guided chemo-photodynamic therapy.

Multifunctional nanodrugs with the integration of precise diagnostic and effective therapeutic functions have shown great promise in improving the efficacy of cancer therapy. We report herein a simple and effective approach to directly assemble an anticancer drug (curcumin), a photodynamic agent (Ce6) and tumor environment-sensitive molecules into cross-linked polyphosphazene and coat on superparamagnetic Fe3O4 nanoclusters to form discrete nanoparticles (termed as FHCPCe NPs). FHCPCe NPs have high physiological stability and good biocompatibility, and can enhance accumulation in tumor tissue via the enhanced permeability and retention effect. Meanwhile, the FHCPCe NPs exhibit an effective performance of dual-modality magnetic resonance imaging (MRI) due to the Fe3O4 cores and fluorescence imaging (FL) in the xenografted HeLa tumor because of the fluorescence of Ce6. Importantly, under the conditions of supernormal glutathione levels and acidic microenvironment in tumor tissue, curcumin and Ce6 can be effectively released by the degradation of FHCPCe NPs. Therefore, excellent anti-tumor effects both in vitro and in vivo have been achieved by synergistic chemotherapy/photodynamic therapy (CT/PDT) using multifunctional NPs. Our study highlights the promise of developing multifunctional nanomaterials for accurate multimodal imaging-guided highly sensitive therapy of cancer.

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.

Correlation of fluorine 18-labeled sodium fluoride uptake and arterial calcification on whole-body PET/CT in cancer patients.

BACKGROUND: Fluorine-18-labeled sodium fluoride (F-NaF) uptake measured with PET in the vessel walls can indicate active microcalcification, a potential biomarker of higher-risk plaques, which are not indicated by macrocalcification measured with computed tomography (CT). The aim of this study was to determine the extent to which F-NaF uptake is correlated with calcification at arterial plaques in cancer patients undergoing whole-body PET/CT imaging. PATIENTS AND METHODS: Image data from 179 patients who underwent F-NaF PET/CT were evaluated retrospectively. Plaques were categorized into four groups by calcium score (CS) on CT: CS1 (≥1000); CS2 (400-999); CS3 (100-399), and CS4 (<100) and into three groups by F-NaF target-to-background ratio (TBR) on PET: TBRlow (≤1.0), TBRmedium (1.0-1.5), and TBRhigh (>1.5). Correlations between F-NaF uptake and CS were evaluated. RESULTS: Plaques with F-NaF uptake or arterial calcification were observed in 122 (76%) of the 179 patients. We found a weak but statistically significant positive correlation between CS and F-NaF uptake. The TBR in CS1 plaques was higher than those in CS3 and CS4 plaques, and the TBR in CS2 plaques was higher than that in CS3 plaques (P<0.05). Compared with patients whose plaques were with F-NaF uptake (TBR>1.5) or arterial calcification (CS>0), patients without plaques of F-NaF uptake or calcification were significantly younger (P=0.00) or with significantly more women (P=0.02). CONCLUSION: Our finding of a weak but significant positive correlation between F-NaF uptake and arterial calcification suggests that F-NaF PET/CT could provide complementary information of active microcalcification for atherosclerosis evaluation in cancer patients.