Early Structural, Biochemical, and Metabolic Responses to Anlotinib in Patients With Progressive Radioactive Iodine Refractory Differentiated Thyroid Cancer.

OBJECTIVE: We aimed to assess the early efficacy of anlotinib in patients with progressive radioactive iodine refractory differentiated thyroid cancer at the structural, biochemical, and metabolic levels. METHODS: Ten eligible patients were prospectively enrolled to receive anlotinib. Their responses were assessed at 6 weeks. Apart from the structural response according to Response Evaluation Criteria in Solid Tumors version 1.1, the biochemical response was assessed by serum thyroglobulin (Tg), and the metabolic response was assessed by 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) according to the European Organization for Research and Treatment of Cancer criteria. A safety profile was recorded. RESULTS: Structurally controlled disease (20% partial response + 80% stable disease) was observed in all patients. The median longest diameter of target lesions shrank from 20.8 mm (IQR, 14.9-27.5) to 17.0 mm (IQR, 14.1-23.7) (P < .001), and the average shrinkage rate was -15.1 ± 14.1%. Sharp serum Tg reduction by 72.8 ± 16.4% was observed in 8 measurable patients. The 18F-FDG PET/CT-mapped glucose metabolic response was not quite comparable to the structural response, with 90% of the patients having controlled disease (30% partial metabolic response + 60% stable metabolic disease), whereas 10% presented progressive metabolic disease. The most common treatment-emergent adverse events (AEs) were hypertension (100%) and proteinuria (70%). Most AEs were grade 1 or 2, whereas grade 3 AEs occurred only in hypertension. CONCLUSION: Anlotinib is generally well tolerated and can bring early disease control within the initial 6 weeks of treatment. The sharp biochemical response suggests Tg to be an early sensitive biomarker to anlotinib, whereas the heterogeneous metabolic response might play a complementary role.

Preoperative 11 C-Methionine PET-MRI in Pediatric Infratentorial Tumors.

PURPOSE: MRI is the main imaging modality for pediatric brain tumors, but amino acid PET can provide additional information. Simultaneous PET-MRI acquisition allows to fully assess the tumor and lower the radiation exposure. Although symptomatic posterior fossa tumors are typically resected, the patient management is evolving and will benefit from an improved preoperative tumor characterization. We aimed to explore, in children with newly diagnosed posterior fossa tumor, the complementarity of the information provided by amino acid PET and MRI parameters and the correlation to histopathological results. PATIENTS AND METHODS: Children with a newly diagnosed posterior fossa tumor prospectively underwent a preoperative 11 C-methionine (MET) PET-MRI. Images were assessed visually and semiquantitatively. Using correlation, minimum apparent diffusion coefficient (ADC min ) and contrast enhancement were compared with MET SUV max . The diameter of the enhancing lesions was compared with metabolic tumoral volume. Lesions were classified according to the 2021 World Health Organization (WHO) classification. RESULTS: Ten children were included 4 pilocytic astrocytomas, 2 medulloblastomas, 1 ganglioglioma, 1 central nervous system embryonal tumor, and 1 schwannoma. All lesions showed visually increased MET uptake. A negative moderate correlation was found between ADC min and SUV max values ( r = -0.39). Mean SUV max was 3.8 (range, 3.3-4.2) in WHO grade 4 versus 2.5 (range, 1.7-3.0) in WHO grade 1 lesions. A positive moderate correlation was found between metabolic tumoral volume and diameter values ( r = 0.34). There was no correlation between SUV max and contrast enhancement intensity ( r = -0.15). CONCLUSIONS: Preoperative 11 C-MET PET and MRI could provide complementary information to characterize pediatric infratentorial tumors.

Nuclear Medicine and Molecular Imaging Applications in Gynecologic Malignancies: A Comprehensive Review.

Gynecologic malignancies, consisting of endometrial, cervical, ovarian, vulvar, and vaginal cancers, pose significant diagnostic and management challenges due to their complex anatomic location and potential for rapid progression. These tumors cause substantial morbidity and mortality, often because of their delayed diagnosis and treatment. An estimated 19% of newly diagnosed cancers among women are gynecologic in origin. In recent years, there has been growing evidence supporting the integration of nuclear medicine imaging modalities in the diagnostic work-up and management of gynecologic cancers. The sensitivity of fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) combined with the anatomical specificity of computed tomography (CT) and magnetic resonance imaging (MRI) allows for the hybrid evaluation of metabolic activity and structural abnormalities that has become an indispensable tool in oncologic imaging. Lymphoscintigraphy, using technetium 99m (99mTc) based radiotracers along with single photon emission computed tomography/ computed tomography (SPECT/CT), holds a vital role in the identification of sentinel lymph nodes to minimize the surgical morbidity from extensive lymph node dissections. While not yet standard for gynecologic malignancies, promising therapeutic nuclear medicine agents serve as specialized treatment options for patients with advanced or recurrent disease. This article aims to provide a comprehensive review on the nuclear medicine applications in gynecologic malignancies through the following objectives: 1) To describe the role of nuclear medicine in the initial staging, lymph node mapping, response assessment, and recurrence/surveillance imaging of common gynecologic cancers, 2) To review the limitations of 18F-FDG PET/CT and promising applications of 18F-FDG PET/MRI in gynecologic malignancy, 3) To underscore the promising theragnostic applications of nuclear medicine, 4) To highlight the current role of nuclear medicine imaging in gynecologic cancers as per the National Comprehensive Cancer Network (NCCN), European Society of Surgical Oncology (ESGO), and European Society of Medical Oncology (ESMO) guidelines.

18F-FDG-PET/CT response after first-line treatment as a prognostic factor for survival in peripheral T-cell lymphoma: a Spanish retrospective study.

BACKGROUND: An accurate assessment of tumor viability after first-line treatment is critical for predicting treatment failure in peripheral T-cell lymphomas (PTCLs). 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has been adopted as the preferred assessment method in clinical trials, but its impact in clinical practice should be examined. This study aims to determine the prognostic significance of18F-FDG-PET/CT for survival following first-line treatment in PTCL patients. RESEARCH DESIGN AND METHODS: Retrospective observational study including 175 patients diagnosed with PTCL between 2008 and 2013 in 13 Spanish sites. RESULTS: Fifty patients were evaluated with18F-FDG-PET/CT following first-line therapy: 58% were18F-FDG-PET/CT-negative and 42% were18F-FDG-PET/CT-positive. Disease progression occurred in 37.9% of18F-FDG-PET/CT-negative patients and in 80.9% of18F-FDG-PET/CT-positive patients (p = 0.0037). Median progression-free survival and overall survival were 67 and 74 months for18F-FDG-PET/CT-negative patients, and 5 (p < 0.0001) and 10 months (p < 0.0001), respectively, in18F-FDG-PET/CT-positive patients. After multivariate analysis, only B symptoms emerged as a negative predictive factor of complete response (RR 7.08; 95% CI 1.60-31.31; p = 0.001). CONCLUSIONS: 18F-FDG-PET/CT identifies high-risk PTCL patients who will have poor prognosis and survival following first-line treatment. However, more research is needed to confirm the best treatment options for PTCL patients.

Assessment of water enema PET/CT: an effective imaging technique for the diagnosis of incidental colorectal 18F-FDG uptake.

BACKGROUND: To validate the feasibility of water enema PET/CT (WE-PET/CT) in incidental colorectal 18F-FDG uptake and improve the accuracy of diagnosing colorectal neoplastic lesions. METHODS: We retrospectively analysed the electronic records of 338 patients undergoing common PET/CT and WE-PET/CT at our hospital. PET/CT results were correlated with colonoscopy pathology and follow-up results. The ROC contrast curve was plotted to evaluate the accuracy of SUVmax on common PET/CT and WE-PET/CT for detecting neoplastic lesions. SUVmax and the median retention indexes (RIs) of cancerous, precancerous, and benign lesions and physiologic uptake were compared. RESULTS: The sensitivity, specificity and accuracy of diagnosing neoplastic lesions with common PET/CT were 84.0%, 78.3% and 80.2%, respectively. The corresponding results with WE-PET/CT were 95.8%, 96.5% and 96.2%. The AUC of SUVmax on WE-PET/CT was significantly higher than that on common PET/CT (0.935 vs. 0.524, p < 0.001). The median SUVmax on WE-PET/CT was significantly higher than that on common PET/CT in cancerous and precancerous lesions, and significantly decreased in benign lesions and physiologic uptake (p < 0.001). The RI was significantly different between cancerous lesions and physiologic uptake, between precancerous lesions and physiologic uptake, between benign lesions and physiologic uptake, and between cancerous and benign lesions (p < 0.05). CONCLUSIONS: WE-PET/CT is a noninvasive, well-tolerated and effective technique for diagnosing incidental colorectal 18F-FDG uptake. It is helpful for a timely colonoscopy and can effectively avoid an unnecessary colonoscopy for incidental colorectal 18F-FDG uptake.

Saengmaeksan, a traditional polyherbal formulation containing Panax ginseng, improves energy metabolism during exercise.

Saengmaeksan (SMS), a representative oriental medicine that contains Panax ginseng Meyer, Liriope muscari, and Schisandra chinensis (1:2:1), is used to improve body vitality and enhance physical activity. However, there is limited scientific evidence to validate the benefits of SMS. Here, we investigated the in vitro and in vivo regulatory effects of SMS and its constituents on energy metabolism and the underlying molecular mechanisms. For this, quantitative real-time polymerase chain reaction, 3D holotomographic microscopy, western blotting, and glucose uptake experiments using 18F-fluoro-2-deoxy-D-glucose (18F-FDG) were performed using L6 cells to investigate in vitro energy metabolism changes. In addition, 18F-fluorocholine (18F-FCH) and 18F-FDG positron emission tomography/computed tomography (PET/CT) analyses, immunohistochemistry, and respiratory gas analysis were performed in mice post-endurance exercise on a treadmill. In the energy metabolism of L6 cells, a significant reversal in glucose uptake was observed in the SMS-treated group, as opposed to an increase in uptake over time compared to the untreated control group. Furthermore, P. ginseng alone and SMS significantly decreased the volume of lipid droplets. SMS also regulated the phosphorylation of extracellular signal-regulated kinase (ERK), phosphorylation of p38, mitochondrial morphology, and the expression of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE/Ref-1) in H2O2-stimulated L6 cells. In addition, SMS treatment was found to regulate whole body and muscle energy metabolism in rats subjected to high-intensity exercise, as well as glucose and lipid metabolism in skeletal muscle. Therefore, SMS containing P. ginseng ameliorated imbalanced energy metabolism through oxidative stress-induced APE/Ref-1 expression. SMS may be a promising supplemental option for metabolic performance.

Asymmetry of thalamic hypometabolism on FDG-PET/CT in neurofibromatosis type 1: Association with peripheral tumor burden.

BACKGROUND AND PURPOSE: Thalamic hypometabolism is a consistent finding in brain PET with F-18 fluorodeoxyglucose (FDG) in patients with neurofibromatosis type 1 (NF1). However, the pathophysiology of this metabolic alteration is unknown. We hypothesized that it might be secondary to disturbance of peripheral input to the thalamus by NF1-characteristic peripheral nerve sheath tumors (PNSTs). To test this hypothesis, we investigated the relationship between thalamic FDG uptake and the number, volume, and localization of PNSTs. METHODS: This retrospective study included 22 adult NF1 patients (41% women, 36.2 ± 13.0 years) referred to whole-body FDG-PET/contrast-enhanced CT for suspected malignant transformation of PNSTs and 22 sex- and age-matched controls. Brain FDG uptake was scaled voxelwise to the individual median uptake in cerebellar gray matter. Bilateral mean and left-right asymmetry of thalamic FDG uptake were determined using a left-right symmetric anatomical thalamus mask. PNSTs were manually segmented in contrast-enhanced CT. RESULTS: Thalamic FDG uptake was reduced in NF1 patients by 2.0 standard deviations (p < .0005) compared to controls. Left-right asymmetry was increased by 1.3 standard deviations (p = .013). Thalamic hypometabolism was higher in NF1 patients with ≥3 PNSTs than in patients with ≤2 PNSTs (2.6 vs. 1.6 standard deviations, p = .032). The impact of the occurrence of paraspinal/paravertebral PNSTs and of the mean PNST volume on thalamic FDG uptake did not reach statistical significance (p = .098 and p = .189). Left-right asymmetry of thalamic FDG uptake was not associated with left-right asymmetry of PNST burden (p = .658). CONCLUSIONS: This study provides first evidence of left-right asymmetry of thalamic hypometabolism in NF1 and that it might be mediated by NF1-associated peripheral tumors.

Endoscopic Evaluation of PET/CT Abnormalities in the Gastrointestinal Tract: Yield and Approach.

BACKGROUND: Unexpected hypermetabolic activity is often encountered in the gastrointestinal tract when PET/CT is performed for various indications, prompting endoscopic evaluation. Our aim was to characterize the types of lesions seen in segments of the gastrointestinal tract with unexpected PET/CT abnormalities as well as clinically significant lesions seen on endoscopy which did not produce a PET/CT abnormality to guide the endoscopist tasked with evaluating these imaging findings. METHODS: We retrospectively reviewed a database of endoscopies performed at City of Hope Comprehensive Cancer Center between January 1, 2016 and September 30, 2021 for an indication of "abnormal PET." We divided the gastrointestinal tract into segments and defined categories of endoscopic/histologic findings for each segment. We counted the number of segments with an abnormal PET/CT finding and corresponding endoscopic/histologic abnormality as well as the number of segments with an endoscopic/histologic abnormality but normal PET/CT. RESULTS: PET/CT identified 209 segments with hypermetabolic activity, 109 of which had corresponding endoscopic/histologic abnormalities. In the jejunum and ileum, all corresponding lesions were malignant. Seventy-three percent of corresponding lesions in the stomach were H. pylori positive. PET/CT failed to detect 34.7% of clinically significant lesions diagnosed endoscopically, including 1 malignancy in the transverse colon and many inflammatory or low-risk premalignant lesions. CONCLUSION: PET/CT abnormalities seen in the small bowel should be evaluated urgently as nearly all correlates were malignant, while abnormalities in the stomach should prompt workup for H. pylori. Most lesions missed by PET/CT were inflammatory or low-risk premalignant yet clinically significant, confirming the need to inspect the entirety of the upper or lower gastrointestinal tract during endoscopy.

Effect of high-dose glucocorticoid treatment on human brown adipose tissue activity: a randomised, double-blinded, placebo-controlled cross-over trial in healthy men.

BACKGROUND: Glucocorticoids (GCs) are widely applied anti-inflammatory drugs that are associated with adverse metabolic effects including insulin resistance and weight gain. Previous research indicates that GCs may negatively impact brown adipose tissue (BAT) activity in rodents and humans. METHODS: We performed a randomised, double-blinded cross-over trial in 16 healthy men (clinicaltrials.govNCT03269747). Participants received 40 mg of prednisone per day for one week or placebo. After a washout period of four weeks, participants crossed-over to the other treatment arm. Primary endpoint was the increase in resting energy expenditure (EE) in response to a mild-cold stimulus (cold-induced thermogenesis, CIT). Secondary outcomes comprised mean 18F-FDG uptake into supraclavicular BAT (SUVmean) as determined by FDG-PET/CT, volume of the BAT depot as well as fat content determined by MRI. The plasma metabolome and the transcriptome of supraclavicular BAT and of skeletal muscle biopsies after each treatment period were analysed. FINDINGS: Sixteen participants were recruited to the trial and completed it successfully per protocol. After prednisone treatment resting EE was higher both during warm and cold conditions. However, CIT was similar, 153 kcal/24 h (95% CI 40-266 kcal/24 h) after placebo and 186 kcal/24 h (95% CI 94-277 kcal/24 h, p = 0.38) after prednisone. SUVmean of BAT after cold exposure was not significantly affected by prednisone (3.36 g/ml, 95% CI 2.69-4.02 g/ml, vs 3.07 g/ml, 95% CI 2.52-3.62 g/ml, p = 0.28). Results of plasma metabolomics and BAT transcriptomics corroborated these findings. RNA sequencing of muscle biopsies revealed higher expression of genes involved in calcium cycling. No serious adverse events were reported and adverse events were evenly distributed between the two treatments. INTERPRETATION: Prednisone increased EE in healthy men possibly by altering skeletal muscle calcium cycling. Cold-induced BAT activity was not affected by GC treatment, which indicates that the unfavourable metabolic effects of GCs are independent from thermogenic adipocytes. FUNDING: Grants from Swiss National Science Foundation (PZ00P3_167823), Bangerter-Rhyner Foundation and from Nora van der Meeuwen-Häfliger Foundation to MJB. A fellowship-grant from the Swiss National Science Foundation (SNF211053) to WS. Grants from German Research Foundation (project number: 314061271-TRR 205) and Else Kröner-Fresenius (grant support 2012_A103 and 2015_A228) to MR.

PSMA-targeted radioligand therapy in prostate cancer: current status and future prospects.

INTRODUCTION: The prostate-specific membrane antigen (PSMA) targeted radioligand therapy (PRLT) for the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients has generated significant interest among the oncologic community, with several publications documenting good response rates and survival benefits with low toxicity profiles. AREAS COVERED: Indications, patient preparation, dose administration, post-treatment imaging, dosimetry, and side effect profiles of 177Lu-PSMA-617 are discussed in this article. We also discuss results from prospective studies, major retrospective studies, meta-analyses, clinical trials, and mentioned major ongoing clinical trials on PRLT. We have also portrayed our own experiences and future perspectives on PRLT. EXPERT OPINION: For PRLT, PSMA-617 and PSMA-I&T molecules have revolutionized the theranostic approach in the management of advanced prostate cancer, with solid backing from several published articles showing favorable outcomes and an excellent safety profile of 177Lu-PSMA-617. Improvement in quality of life and survival was seen in the majority of mCRPC patients after 177Lu-PSMA-617 PRLT. Patients with good performance status, asymptomatic, only lymph node metastases, high PSMA expressing lesions, and no discordant FDG avid lesions have a longer survival after 177Lu-PSMA-617 PRLT than patients with poor performance status, symptomatic, hepatic, brain, and skeletal metastases, discordant PSMA, and FDG-avid lesions. Docetaxel and cabazitaxel are approved treatments for mCRPC patients. 177Lu-PSMA-617 is approved as a third-line systemic treatment for mCRPC patients with failure to respond to androgen receptor pathway inhibitors and docetaxel therapy. PRLT is a safe and effective alternative to cabazitaxel (third-line systemic treatment), but it has a higher cost. 177Lu-PSMA-617 could be a more efficient therapeutic option for mCRPC patients as first-line or combined therapy, and it may be a useful therapeutic option for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) patients. Several clinical studies and clinical trials on PRLT are currently underway. In the future, the results of these trials will be helpful in evolving treatment strategies for prostate cancer patients.

In vivo imaging of acute physiological responses after treatment of cancer with near-infrared photoimmunotherapy.

PURPOSE: Near-infrared photoimmunotherapy (NIR-PIT) is a new cancer phototherapy using an antibody-photosensitizer conjugate (Ab-IR700). By NIR light irradiation, Ab-IR700 forms a water-insoluble aggregation on the plasma membrane of cancer cells, leading to lethal membrane damage of cancer cells with high selectivity. However, IR700 produces singlet oxygen, which induces non-selective inflammatory responses such as edema in normal tissues around the tumor. Understanding such treatment-emergent responses is important to minimize side effects and improve clinical outcomes. Thus, in this study, we evaluated physiological responses during NIR-PIT by magnetic resonance imaging (MRI) and positron emission tomography (PET). PROCEDURES: Ab-IR700 was intravenously injected into tumor-bearing mice with two tumors on the right and left sides of the dorsum. At 24 h after injection, a tumor was irradiated with NIR light. Edema formation was examined by T1/T2/diffusion-weighted MRI and inflammation was investigated by PET with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). Because inflammation can increase vascular permeability via inflammatory mediators, we evaluated changes in oxygen levels in tumors using a hypoxia imaging probe, [18F]fluoromisonidazole ([18F]FMISO). RESULTS: The uptake of [18F]FDG in the irradiated tumor was significantly decreased compared to the control tumor, indicating the impairment of glucose metabolism induced by NIR-PIT. MRI and [18F]FDG-PET images showed that inflammatory edema with [18F]FDG accumulation was present in the surrounding normal tissues of the irradiated tumor. Furthermore, [18F]FMISO accumulation in the center of the irradiated tumor was relatively low, indicating the enhancement of oxygen supply due to increased vascular permeability. In contrast, high [18F]FMISO accumulation was observed in the peripheral region, indicating enhancement of hypoxia in the region. This could be because inflammatory edema was formed in the surrounding normal tissues, which blocked blood flow to the tumor. CONCLUSIONS: We successfully monitored inflammatory edema and changes in oxygen levels during NIR-PIT. Our findings on the acute physiological responses after light irradiation will help to develop effective measures to minimize the side effects in NIR-PIT.

The value of 18F-FDG PET/CT in the systemic evaluation of patients with Rosai-Dorfman disease: a retrospective study and literature review.

BACKGROUND: Rosai-Dorfman disease (RDD) is a rare form of non-Langerhans cell histiocytic disease. The aim of this study was to review the characteristics of RDD using 18F-FDG PET/CT and determine its efficacy in the disease management. RESULTS: A total of 28 RDD patients underwent 33 18F-FDG PET/CT scans for systematic assessment and follow-up. The common involved sites included the lymph nodes (17, 60.7%), upper respiratory tract (11, 39.3%), and skin (9, 32.1%). Five patients had more lesions detected in PET/CT images than in CT and/or MRI, including inapparent nodules (n = 5) and bone destruction (n = 3). After thorough treatment evaluation using PET/CT, the treatment strategies of 14 patients (14/16, 87.5%) were changed. Five patients underwent PET/CT twice during follow-up and the SUVs were significantly decreased (15.3 ± 3.4 vs. 4.4 ± 1.0, p = 0.02), which demonstrated disease improvement. CONCLUSIONS: 18F-FDG PET/CT contributed to displaying the holistic characteristics of RDD, in particular during initial assessment, treatment strategy adjustment, or efficacy evaluation, and could compensate for some disadvantages of CT and MRI images.

Bone Metastases Detection in Patients with Breast Cancer: Does Bone Scintigraphy Add Information to PET/CT?

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) has become in recent years a tool for breast cancer (BC) staging. However, its accuracy to detect bone metastases is classically considered inferior to bone scintigraphy (BS). The purpose of this work is to compare the effectiveness of bone metastases detection between PET/CT and BS. MATERIALS AND METHODS: Prospective study of 410 female patients treated in a Comprehensive Cancer Center between 2014 and 2020 that performed PET/CT and BS for staging purposes. The image analysis was performed by 2 senior nuclear medicine physicians. The comparison was performed based on accuracy, sensitivity, and specificity on a patient and anatomical region level and was assessed using McNemar's Test. An average ROC was calculated for the anatomical region analysis. RESULTS: PET/CT presented higher values of accuracy and sensitivity (98.0% and 93.83%), surpassing BS (95.61% and 81.48%) in detecting bone disease. There was a significant difference in favor of PET/CT (sensitivity 93.83% vs. 81.48%), however, there is no significant difference in eliminating false positives (specificity 99.09% vs. 99.09%). PET/CT presented the highest accuracy and sensitivity values for most of the bone segments, only surpassed by BS for the cranium. There was a significant difference in favor of PET/CT in the upper limb, spine, thorax (sternum) and lower limb (pelvis and sacrum), and in favor of BS in the cranium. The ROC showed that PET/CT has a higher sensitivity and consistency across the bone segments. CONCLUSION: With the correct imaging protocol, PET/CT does not require BS for patients with BC staging.

Prognostic value of metabolic tumor volume and lesion dissemination from baseline PET/CT in patients with diffuse large B-cell lymphoma: Further risk stratification of the group with low-risk and high-risk NCCN-IPI.

PURPOSE: The purpose of this study was to determine the prognostic value of metabolic tumor volume and lesion dissemination from baseline PET/CT in patients with diffuse large B-cell lymphoma (DLBCL) and the prognostic value of them in the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) subgroups. METHODS: A total of 113 patients who underwent 18F-FDG PET/CT examination in our institution were retrospectively collected. The MTV was measured by iterative adaptive algorithm. The location of the lesion was obtained according to its three-dimensional coordinates, and Dmax was obtained. SDmax is derived from Dmax standardized by body surface area (BSA). The X-tile method was used to determine the optimal cut-off values for MTV, Dmax and SDmax. Cox regression analysis was used to perform univariate and multivariate analyses. Patient survival rates were derived from Kaplan-Meier curves and compared using the log-rank test. RESULTS: The median follow-up time was 24 months. The median of MTV was 196.86 cm3 (range 2.54-2925.37 cm3), and the optimal cut-off value was 489 cm3. The median of SDmax was 0.25 m-1 (range 0.12-0.51 m-1), and the best cut-off value was 0.31 m-1. MTV and SDmax were independent prognostic factors of PFS (all P < 0.001). Combined with MTV and SDmax, the patients were divided into three groups, and the difference of PFS among the groups was statistically significant (P < 0.001), and was able to stratify the risk of NCCN-IPI patients in the low-risk (NCCN-IPI < 4) and high-risk (NCCN-IPI ≥ 4) groups (P = 0.001 and P = 0.031). CONCLUSION: MTV and SDmax are independent prognostic factors for PFS in DCBCL patients, which describe tumor burden and tumor dissemination characteristics, respectively. The combination of the two could facilitate risk stratification between the low-risk and high-risk NCCN-IPI groups.

Diagnostic Performance of Response Assessment FDG-PET/CECT in HNSCC Treated With Definitive Radio(chemo)therapy Using NI-RADS.

OBJECTIVE: To assess the diagnostic performance of response assessment 18F-fluorodeoxyglucose positron emission tomography/contrast-enhanced computed tomography (FDG-PET/CECT) following definitive radio(chemo)therapy in head and neck squamous cell carcinoma (HNSCC) using Neck Imaging Reporting and Data System (NI-RADS). STUDY DESIGN: A retrospective analysis from a prospectively maintained dataset. SETTING: Tertiary-care comprehensive cancer center in a low-middle-income country. METHODS: Adults with newly diagnosed, biopsy-proven, nonmetastatic HNSCC treated with definitive radio(chemo)therapy were included. Posttreatment response assessment FDG-PET/CECT scans were retrospectively assigned NI-RADS categories (1-3) for the primary site, neck, and both sites combined. Locoregional recurrence occurring within 2-years was defined as the event of interest. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were calculated. Locoregional control stratified by NI-RADS categories was computed with the Kaplan-Meier method and compared using the log-rank test. RESULTS: Posttreatment FDG-PET/CECT scans were available in 190 patients constituting the present study cohort. Sensitivity, specificity, PPV, NPV, and overall accuracy of the NI-RADS template for the primary site was 73.5%, 81.4%, 46.3%, 93.4%, and 80.0%, respectively. Similar metrics for the neck were 72.7%, 87.5%, 43.2%, 96.1%, and 85.8%, respectively. Combining primary site and neck, the corresponding metrics of diagnostic accuracy were 84.4%, 69.7%, 46.3%, 93.5%, and 73.2%, respectively. At a median follow-up of 40 months, Kaplan-Meier estimates of 2-year locoregional control were significantly higher for NI-RADS category 1 (94.2%) compared to NI-RADS category 2 (69.4%) and category 3 (20.4%), respectively (stratified log-rank p < .0001). CONCLUSION: FDG-PET/CECT using the NI-RADS template is associated with good diagnostic performance and prognostic utility in HNSCC treated with definitive radio(chemo)therapy.

Positron Emission Tomography-Based Immunoimaging for Cancer Patient Stratification: Toward a More Holistic Approach.

Immunotherapy with immune checkpoint inhibitors (ICIs) changed the treatment management in several solid metastatic tumors with very poor prognosis, in particular in melanoma stage IV since its introduction in 2011. However, it is not yet fully understood why some patients respond to ICIs and others not, and it is also unclear why melanomas are the most sensitive tumors to ICI treatment. Selection criteria for patient stratification are needed and several approaches are under evaluation. These include the PD-L1 expression in the tumor samples, assessment of the tumor mutational burden as well as radiological and molecular imaging techniques, such as positron emission tomography (PET)-CT and PET-MRI with 18F-fluorodeoxyglucose (FDG) or novel radiopharmaceuticals. In the near future, a more holistic approach based on the combination of imaging data and sequencing data and the development of radiogenomic signatures will be needed for a better characterization of immunotherapy response and selection of patients who will benefit from ICI therapy alone or in combination with chemotherapy.

Imaging of Anal Squamous Cell Carcinoma: Survey Results and Expert Opinion from the Rectal and Anal Cancer Disease-Focused Panel of the Society of Abdominal Radiology.

The role and method of image-based staging of anal cancer has evolved with the rapid development of newer imaging modalities and the need to address the rising incidence of this rare cancer. In 2014, the European Society of Medical Oncology mandated pelvic magnetic resonance imaging (MRI) for anal cancer and subsequently other societies such as the National Comprehensive Cancer Network followed suit with similar recommendations. Nevertheless, great variability exists from center to center and even within individual centers. Notably, this is in stark contrast to the imaging of the anatomically nearby rectal cancer. As participating team members for this malignancy, we embarked on a comprehensive literature review of anal cancer imaging to understand the relative merits of these new technologies which developed after computed tomography (CT), e.g., MRI and positron emission tomography/computed tomography (PET/CT). The results of this literature review helped to inform our next stage: questionnaire development regarding the imaging of anal cancer. Next, we distributed the questionnaire to members of the Society of Abdominal Radiology (SAR) Rectal and Anal Disease-Focused Panel, a group of abdominal radiologists with special interest, experience, and expertise in rectal and anal cancer, to provide expert radiologist opinion on the appropriate anal cancer imaging strategy. In our expert opinion survey, experts advocated the use of MRI in general (65% overall and 91-100% for primary staging clinical scenarios) and acknowledged the superiority of PET/CT for nodal assessment (52-56% agreement for using PET/CT in primary staging clinical scenarios compared to 30% for using MRI). We therefore support the use of MRI and PET and suggest further exploration of PET/MRI as an optimal combined evaluation. Our questionnaire responses emphasized the heterogeneity in imaging practice as performed at numerous academic cancer centers across the United States and underscore the need for further reconciliation and establishment of best imaging practice guidelines for optimized patient care in anal cancer.

Visualizing increased uptake of [18F]FDG and [18F]FTHA in kidneys from obese high-fat diet fed C57BL/6J mice using PET/CT ex vivo.

It is known that high-fat diet (HFD) and/or diabetes may influence substrate preferences and energy demands in the heart preceding diabetic cardiomyopathy. They may also induce structural glomerular changes causing diabetic nephropathy. PET/CT has been utilized to examine uptake of energy substrates, and to study metabolic changes or shifts before onset of metabolic disorders. However, conventional PET/CT scanning of organs with relatively low uptake, such as the kidney, in small animals in vivo may render technical difficulties. To address this issue, we developed a PET/CT ex vivo protocol with radiolabeled glucose and fatty acid analouges, [18F]FDG and [18F]FTHA,to study substrate uptake in mouse kidneys. We also aimed to detect a possible energy substrate shift before onset of diabetic nephropathy. The ex vivo protocol reduced interfering background as well as interindividual variances. We found increased uptake of [18F]FDG and [18F]FTHA in kidneys after HFD, compared to kidneys from young mice on standard chow. Levels of kidney triglycerides also increased on HFD. Lipoprotein lipase (LPL) activity, the enzyme responsible for release of fatty acids from circulating lipoproteins, is normally increased in postprandial mice kidneys. After long-term HFD, we found that LPL activity was suppressed, and could therefore not explain the increased levels of stored triglycerides. Suppressed LPL activity was associated with increased expression of angiopoietin-like protein4, an inhibitor of LPL. HFD did not alter the transcriptional control of some common glucose and fatty acid transporters that may mediate uptake of [18F]FDG and [18F]FTHA. Performing PET/CT ex vivo reduced interfering background and interindividual variances. Obesity and insulin resistance induced by HFD increased the uptake of [18F]FDG and [18F]FTHA and triglyceride accumulation in mouse kidneys. Increased levels of [18F]FDG and [18F]FTHA in obese insulin resistant mice could be used clinically as an indicator of poor metabolic control, and a complementary test for incipient diabetic nephropathy.

Artificial Intelligence in Breast Cancer: A Systematic Review on PET Imaging Clinical Applications.

BACKGROUND: 18F-FDG PET/CT imaging represents the most important functional imaging method in oncology. European Society of Medical Oncology and the National Comprehensive Cancer Network guidelines defined a crucial role of 18F-FDG PET/CT imaging for local/locally advanced breast cancer. The application of artificial intelligence on PET images might potentially contributes in the field of precision medicine. OBJECTIVE: This review aims to summarize the clinical indications and limitations of PET imaging for comprehensive artificial intelligence in relation to breast cancer subtype, hormone receptor status, proliferation rate, and lymphonodal (LN)/distant metastatic spread, based on recent literature. METHODS: A literature search of the Pubmed/Scopus/Google Scholar/Cochrane/EMBASE databases was carried out, searching for articles on the use of artificial intelligence and PET in breast tumors. The search was updated from January 2010 to October 2021 and was limited to original articles published in English and about humans. A combination of the search terms "artificial intelligence", "breast cancer", "breast tumor", "PET", "Positron emission tomography", "PET/CT", "PET/MRI", "radiomic"," texture analysis", "machine learning", "deep learning" was used. RESULTS: Twenty-three articles were selected following the PRISMA criteria from 139 records obtained from the Pubmed/Scopus/Google Scholar/Cochrane/EMBASE databases according to our research strategy. The QUADAS of 30 full-text articles assessed reported seven articles that were excluded for not being relevant to population and outcomes and/or for lower level of evidence. The majority of papers were at low risk of bias and applicability. The articles were divided per topic, such as the value of PET in the staging and re-staging of breast cancer patients, including new radiopharmaceuticals and simultaneous PET/MRI. CONCLUSION: Despite the current role of AI in this field remains still undefined, several applications for PET/CT imaging are under development, with some preliminary interesting results particularly focused on the staging phase that might be clinically translated after further validation studies.

Basic characteristics of magnesium-coal slag solid waste backfill material: Part I. preliminary study on flow, mechanics, hydration and leaching characteristics.

The environmental damage caused by surface subsidence and coal-based solid waste (CBSW) is a common problem in the process of coal mining. Backfill mining can control the mining-induced subsidence and solve the problem of bulk solid waste storage. In the present work, a magnesium-coal slag solid waste backfill material (MCB) with modified magnesium slag (MS) as binder and CBSW (fly ash (FA), flue gas desulfurization gypsum (FDG) and coal gasification slag (CGS)) as supplementary cementitious material/aggregate was proposed to meet the needs of coal mining in Northern Shaanxi, China, to realize the comprehensive treatment of goaf and CBSW. The results show that: (1) The rheological curve of the fresh MCB slurry is highly consistent with the Herschel-Bulkley (H-B) model, and its fluidity meets the basic requirements of mine backfill pumping. With the addition of FDG and MS, the yield stress, apparent viscosity and thixotropy of MCB slurry increase, while the pseudoplastic index and slump decrease. (2) The strength of MCB develops slowly in the early stage (0∼14 days) and increases rapidly in the later stage (14∼90 days). Except for the ratio of M20F1 and FDG = 0%, the strength of samples at other ratios (at 28 days) is between 6.06∼11.68 MPa, which meets the strength requirement of 6 MPa for coal mine backfill. The addition of MS and appropriate amount of FDG is beneficial to the development of strength. In contrast, MS exhibits a significant improvement in early strength, and FDG has a significant improvement in late-age strength. (3) Corresponding to the compressive strength, the hydration products C-S(A)-H and AFt of MCB are less in the early stage and greatly increased in the later stage. The active substance in FA/CGS will undergo pozzolanic reaction with the MS hydration product CH. The addition of FDG and MS can promote the reaction and increase the amount of hydration product, but in contrast, the promotion effect of FDG is more significant. (4) The amount of heavy metal leaching of MCB meets the requirements of national standards. The hardened MCB has a solidification/stabilization effect on heavy metal elements, which can significantly reduce the amount of heavy metal leaching. The results imply that MCB is a safe, reliable, and eco-friendly solid waste backfill material, and its application is conducive to the coordinated development of coal resource mining and environmental protection.