Recent Update on PET/CT Radiotracers for Imaging Cerebral Glioma.

Positron emission tomography/computed tomography (PET/CT) has dramatically altered the landscape of noninvasive glioma evaluation, offering complementary insights to those gained through magnetic resonance imaging (MRI). PET/CT scans enable a multifaceted analysis of glioma biology, supporting clinical applications from grading and differential diagnosis to mapping the full extent of tumors and planning subsequent treatments and evaluations. With a broad array of specialized radiotracers, researchers and clinicians can now probe various biological characteristics of gliomas, such as glucose utilization, cellular proliferation, oxygen deficiency, amino acid trafficking, and reactive astrogliosis. This review aims to provide a recent update on the application of versatile PET/CT radiotracers in glioma research and clinical practice.

[18F]FDG PET/CT is useful in discriminating invasive adenocarcinomas among pure ground-glass nodules: comparison with CT findings-a bicenter retrospective study.

PURPOSE: Predicting the malignancy of pure ground-glass nodules (GGNs) using CT is challenging. The optimal role of [18F]FDG PET/CT in this context has not been clarified. We compared the performance of [18F]FDG PET/CT in evaluating GGNs for predicting invasive adenocarcinomas (IACs) with CT. METHODS: From June 2012 to December 2020, we retrospectively enrolled patients with pure GGNs on CT who underwent [18F]FDG PET/CT within 90 days. Overall, 38 patients with 40 ≥ 1-cm GGNs were pathologically confirmed. CT images were analyzed for size, attenuation, uniformity, shape, margin, tumor-lung interface, and internal/surrounding characteristics. Visual [18F]FDG positivity, maximum standardized uptake value (SUVmax), and tissue fraction-corrected SUVmax (SUVmaxTF) were evaluated on PET/CT. RESULTS: The histopathology of the 40 GGNs were: 25 IACs (62.5%), 9 minimally invasive adenocarcinomas (MIA, 22.5%), and 6 adenocarcinomas in situ (AIS, 15.0%). No significant differences were found in CT findings according to histopathology, whereas visual [18F]FDG positivity, SUVmax, and SUVmaxTF were significantly different (P=0.001, 0.033, and 0.018, respectively). The size, visual [18F]FDG positivity, SUVmax, and SUVmaxTF showed significant diagnostic performance to predict IACs (area under the curve=0.693, 0.773, 0.717, and 0.723, respectively; P=0.029, 0.001, 0.018, and 0.013, respectively). In the multivariate logistic regression analysis, visual [18F]FDG positivity discriminated IACs among GGNs among various CT and PET findings (P=0.008). CONCLUSIONS: [18F]FDG PET/CT demonstrated superior diagnostic performance compared to CT in differentiating IAC from AIS/MIA among pure GGNs, thus it has the potential to guide the proper management of patients with pure GGNs.

ChatGPT-assisted deep learning for diagnosing bone metastasis in bone scans: Bridging the AI Gap for Clinicians.

Background: Bone scans are often used to identify bone metastases, but their low specificity may necessitate further studies. Deep learning models may improve diagnostic accuracy but require both medical and programming expertise. Therefore, we investigated the feasibility of constructing a deep learning model employing ChatGPT for the diagnosis of bone metastasis in bone scans and to evaluate its diagnostic performance. Method: We examined 4626 consecutive cancer patients (age, 65.1 ± 11.3 years; 2334 female) who had bone scans for metastasis assessment. A nuclear medicine physician developed a deep learning model using ChatGPT 3.5 (OpenAI). We employed ResNet50 as the backbone network and compared the diagnostic performance of four strategies (original training set, original training set with 1:10 class weight, 10-fold data augmentation for positive images only, and 10-fold data augmentation for all images) to address the class imbalance. We used a class activation map algorithm for visualization. Results: Among the four strategies, the deep learning model with 10-fold data augmentation for positive cases only, using a batch size of 16 and an epoch size of 150, achieved the area under curve of 0.8156, the sensitivity of 56.0 %, and specificity of 88.7 %. The class activation map indicated that the model focused on disseminated bone metastases within the spine but might confuse them with benign spinal lesions or intense urinary activity. Conclusions: Our study illustrates that a clinical physician with rudimentary programming skills can develop a deep learning model for medical image analysis, such as diagnosing bone metastasis in bone scans using ChatGPT. Model visualization may offer guidance in enhancing deep learning model development, including preprocessing, and potentially support clinical decision-making processes.

Is Prone Position [18F]FDG PET/CT Useful in Reducing Respiratory Motion Artifacts in Evaluating Hepatic Lesions?

Prone position is useful in reducing respiratory motion artifacts in lung nodules on 2-Deoxy-2-[18F] fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT). However, whether prone position PET/CT is useful in evaluating hepatic lesions is unknown. Thirty-five hepatic lesions from 20 consecutive patients were evaluated. The maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) of both standard supine position PET/CT and additional prone position PET/CT were evaluated. No significant difference in SUVmax (4.41 ± 2.0 vs. 4.23 ± 1.83; p = 0.240) and MTV (5.83 ± 6.69 vs. 5.95 ± 6.24; p = 0.672) was observed between supine position PET/CT and prone position PET/CT. However, SUVmax changes in prone position PET/CT varied compared with those in supine position PET/CT (median, -4%; range: -30-71%). Prone position PET/CT was helpful when [18F]FDG uptake of the hepatic lesions was located outside the liver on supine position PET/CT (n = 4, SUVmax change: median 15%; range: 7-71%) and there was more severe blurring on supine position PET/CT (n = 6, SUVmax change: median 11%; range: -3-32%). Unlike in lung nodules, prone position PET/CT is not always useful in evaluating hepatic lesions, but it may be helpful in individual cases such as hepatic dome lesions.

Tissue Fraction Correction and Visual Analysis Increase Diagnostic Sensitivity in Predicting Malignancy of Ground-Glass Nodules on [18F]FDG PET/CT: A Bicenter Retrospective Study.

We investigated the role of [18F]FDG positron emission tomography/computed tomography (PET/CT) in evaluating ground-glass nodules (GGNs) by visual analysis and tissue fraction correction. A total of 40 pathologically confirmed ≥1 cm GGNs were evaluated visually and semiquantitatively. [18F]FDG uptake of GGN distinct from background lung activity was considered positive in visual analysis. In semiquantitative analysis, we performed tissue fraction correction for the maximum standardized uptake value (SUVmax) of GGN. Of the 40 GGNs, 25 (63%) were adenocarcinomas, 9 (23%) were minimally invasive adenocarcinomas (MIAs), and 6 (15%) were adenocarcinomas in situ (AIS). On visual analysis, adenocarcinoma showed the highest positivity rate among the three pathological groups (88%, 44%, and 17%, respectively). Both SUVmax and tissue-fraction−corrected SUVmax (SUVmaxTF) were in the order of adenocarcinoma > MIA > AIS (p = 0.033 and 0.018, respectively). SUVmaxTF was significantly higher than SUVmax before correction (2.4 [1.9−3.0] vs. 1.3 [0.8−1.8], p < 0.001). When using a cutoff value of 2.5, the positivity rate of GGNs was significantly higher in SUVmaxTF than in SUVmax (50% vs. 5%, p < 0.001). The diagnostic sensitivity of [18F]FDG PET/CT in predicting the malignancy of lung GGN was improved by tissue fraction correction and visual analysis.

Metabolic tumour volume on 18F-FDG PET/CT predicts extended pathological T stages in patients with renal cell carcinoma at staging.

We evaluated the predictive value of 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/CT (PET/CT) for extended pathological T (pT) stages (≥ pT3a) in Renal cell carcinoma (RCC) patients at staging. Thirty-eight RCC patients who underwent 18F-FDG PET/CT at staging, followed by radical nephrectomy between September 2016 and September 2018, were included in this prospective study. Patients were classified into two groups (limited pT stage: stage T1/2, n = 17; extended pT stage: T3/4, n = 21). Univariate and multivariate logistic regression analyses were performed to identify clinicopathological and metabolic variables to predict extended pT stages. 18F-FDG metabolic parameters were compared in relation to International Society of Urological Pathology (ISUP) grade and lymphovascular invasion (LVI). In univariate analysis, maximum standardised uptake value, metabolic tumour volume (MTV), and ISUP grade were significant. In multivariate analysis, MTV was the only significant factor of extended pT stages. With a cut-off MTV of 21.2, an area under the curve was 0.944, which was higher than 0.824 for clinical T stages (p = 0.037). In addition, high MTV, but not tumour size, was significantly correlated with aggressive pathologic features (ISUP grade and LVI). High glycolytic tumour volume on 18F-FDG PET/CT in RCC patients at staging is predictive of extended pT stages which could aid decision-making regarding the best type of surgery.

The Value of 18F-FDG PET/CT in Evaluating Disease Severity and Prognosis in Idiopathic Pulmonary Fibrosis Patients.

BACKGROUND: Several parameters are useful for assessing disease severity in idiopathic pulmonary fibrosis (IPF); however, the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is not well-defined. We aimed to evaluate the value of 18F-FDG PET/CT for assessing disease severity and prognosis in IPF patients. METHODS: Clinical data of 89 IPF patients (mean age: 68.1 years, male: 94%) who underwent 18F-FDG PET/CT for evaluation of lung nodules or cancer staging were retrospectively reviewed. Mean and maximal standardized uptake values (SUVmean, SUVmax, respectively) were measured in the fibrotic area. Adjusted SUV, including SUV ratio (SUVR, defined as SUVmax-to-liver SUVmean ratio), tissue fraction-corrected SUVmean (SUVmeanTF), and SUVR (SUVRTF), and tissue-to-blood ratio (SUVmax/SUVmean venous; TBRblood) were obtained. Death was defined as the primary outcome, and associations between other clinical parameters (lung function, exercise capacity, C-reactive protein [CRP] level) were also investigated. RESULTS: All SUV parameters were inversely correlated with the forced vital capacity, diffusing capacity for carbon monoxide, and positively correlated with CRP level and the gender-age-physiology index. The SUVmean, SUVmax, and SUVmeanTF were associated with changes in lung function at six months. The SUVR (hazard ratio [HR], 1.738; 95% confidence interval [CI], 1.011-2.991), SUVRTF (HR, 1.441; 95% CI, 1.000-2.098), and TBRblood (HR, 1.377; 95% CI, 1.038-1.827) were significant predictors for mortality in patients with IPF in the univariate analysis, but not in the multivariate analysis. CONCLUSION: 18F-FDG PET/CT may provide additional information on the disease severity and prognosis in IPF patients, and the SUVR may be superior to other SUV parameters.

18F-FDG PET/CT predicts acute exacerbation in idiopathic pulmonary fibrosis after thoracic surgery.

BACKGROUND: Acute exacerbation (AE) is the most lethal postoperative complication in idiopathic pulmonary fibrosis (IPF); however, prediction before surgery is difficult. We investigated the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in predicting postoperative AE in IPF. METHOD: Clinical data of 48 IPF patients who underwent 18F-FDG PET/CT before thoracic surgery were retrospectively analyzed. Mean and maximal standardized uptake values (SUVmean and SUVmax, respectively) were measured in the fibrotic area. Additionally, adjusted values-SUV ratio (SUVR, defined as SUVmax-to-liver SUVmean ratio), tissue fraction-corrected SUVmean (SUVmeanTF), and SUVR (SUVRTF)-were calculated. RESULTS: The mean age of the subjects was 67.8 years and 91.7% were male. After thoracic surgery, 21 (43.8%) patients experienced postoperative complications including prolonged air leakage (29.2%), death (14.6%), and AE (12.5%) within 30 days. Patients who experienced AE showed higher SUVmax, SUVR, SUVmeanTF, and SUVRTF than those who did not, but other clinical parameters were not different between patients with and without AE. The SUV parameters did not differ for other complications. The SUVR (odds ratio [OR] 29.262; P = 0.030), SUVmeanTF (OR 3.709; P = 0.041) and SUVRTF (OR 20.592; P = 0.017) were significant predicting factors for postoperative AE following a multivariate logistic regression analysis. On receiver operating characteristics curve analysis, SUVRTF had the largest area under the curve (0.806, P = 0.007) for predicting postoperative AE among SUV parameters. CONCLUSIONS: Our findings suggest that 18F-FDG PET/CT may be useful in predicting postoperative AE in IPF patients and among SUVs, SUVRTF is the best parameter for predicting postoperative AE in IPF patients.

Glycolysis on F-18 FDG PET/CT Is Superior to Amino Acid Metabolism on C-11 Methionine PET/CT in Identifying Advanced Renal Cell Carcinoma at Staging.

We evaluated the value of F-18 fluorodeoxyglucose (FDG) and C-11 methionine positron emission tomography/computed tomography (PET/CT) to predict high-Fuhrman grade and advanced-stage tumours in patients with renal cell carcinoma (RCC). Forty patients with RCC underwent F-18 FDG and C-11 methionine PET/CT between September 2016 and September 2018. They were classified into limited (stages I and II, n = 15) or advanced stages (stages III and IV, n = 25) according to pathological staging. Logistic regressions were used to predict the advanced stage using various parameters, including maximum standardised uptake value (SUVmax) and metabolic tumour volume (MTV). Receiver operating characteristic analyses were performed to predict high-grade tumours (Fuhrman 3 and 4). On univariate analysis, tumour size, SUVmax and MTV of F-18 FDG and C-11 methionine, and Fuhrman grades were significant predictors for the advanced stage. On multivariate analysis, F-18 FDG MTV > 21.3 cm3 was the most significant predictor (p < 0.001). The area under the curve for predicting high-grade tumours was 0.830 for F-18 FDG (p < 0.001) and 0.726 for C-11 methionine PET/CT (p = 0.014). In conclusion, glycolysis on F-18 FDG PET/CT and amino acid metabolism on C-11 methionine PET/CT were variable but increased in high-grade RCCs. Increased MTV on F-18 FDG PET/CT is a powerful predictor of advanced-stage tumours.

A practical individualized radiation precaution based on the dose rate at release time after inpatient 131I ablation therapy.

INTRODUCTION: Retained radioactivity of 131I after ablation therapy largely differs in each patient according to factors including the amount of remnant thyroid tissue, renal function, and use of recombinant human thyroid-stimulating hormone. To reduce unnecessary restriction of patient's daily life after inpatient 131I ablation therapy, we propose a practical individualized method for radiation precaution based on dose rate at release time. METHODS: We evaluated 215 patients with differentiated thyroid cancer who underwent inpatient 131I ablation therapy following total thyroidectomy. Effective dose equivalent rates at 1-m distance were measured upon release (EDRR) on day 2 and during delayed whole-body scan (EDRD) visits on day 6‒8 after 131I administration. The biexponential model was designed to estimate total effective dose equivalent to others. To assess conservativeness of our model, EDRD estimated by our model was compared with measured EDRD. EDRR-based periods of precaution not to receiving 1 mSv of radiation exposure were estimated and compared with those based on administered radioactivities on American Thyroid Association (ATA) recommendations. RESULTS: The EDRR ranged from 1.0-48.9 µSv/hr. The measured EDRD were equal to or lower than estimated EDRD in all patients, except for one, indicating that our model is sufficiently conservative. According to our model, no subjects needed additional daytime restriction after release. The maximum permissible times for public transportation use were longer in all patients compared with those based on administered radioactivities. Nighttime restriction periods were significantly shorter than those based on administered radioactivity; median periods requiring sleeping apart were 0 (range, 0‒5), 4 (range, 1‒14), and 3 (range, 2‒13) days after release in patients treated with radioactivity doses of 2.96, 5.50, and 7.40 GBq, respectively, needing 8, 16, and 19 additional days, respectively, based on administered radioactivity. CONCLUSIONS: Radiation safety instructions using proposed method based on EDRR of individual patient could safely reduce the burden of radiation precaution.

Prone position [18F]FDG PET/CT to reduce respiratory motion artefacts in the evaluation of lung nodules.

OBJECTIVES: 2-Deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron-emission tomography/computed tomography (PET/CT) is widely used to evaluate lung nodules, although respiratory motion artefacts may occur. We investigated the value of prone position PET/CT (pPET/CT) in lung nodule evaluation compared with standard supine position PET/CT (sPET/CT). METHODS: We retrospectively reviewed 28 consecutive patients (20 men; age, 65.6 ± 12.1 years) with a lung nodule (size, 16.8 ± 5.5 mm) located below the sub-carinal level who underwent [18F]FDG PET/CT in a standard supine position and additional prone position. The maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV), difference of diaphragm position between PET and CT (DDP), Dice's similarity coefficient (DSC) and occurrence of mis-registration were analysed. The [18F]FDG uptake of 20 biopsy-confirmed (15 malignant) nodules was evaluated visually. RESULTS: pPET/CT yielded a significantly higher SUVmax, lower MTV and shorter DDP than with sPET/CT (p = 0.043, 0.007 and 0.021, respectively). Mis-registration occurred in 53.6% of cases in sPET/CT and in 28.6% of cases in pPET/CT (p = 0.092). Among the 15 patients with mis-registration in sPET/CT, 10 patients (66.7%) did not show mis-registration in pPET/CT. DSC was higher in pPET/CT than in sPET/CT in 18 out of 28 patients (64.3%). In visual analysis, malignant nodules exhibited a higher [18F]FDG uptake positivity than benign nodules in pPET/CT (93.3% vs. 40.0%, p = 0.032) but not in sPET/CT (80.0% vs. 40.0%, p = 0.131). CONCLUSIONS: pPET/CT reduces respiratory motion artefact and enables more-precise measurements of PET parameters. KEY POINTS: • In prone position PET/CT, the decrease in the blurring effect caused by reduced respiratory motion resulted in a higher SUVmax and lower MTV in lung nodules than that with supine position PET/CT. • Prone position PET/CT was useful to interpret correctly malignant lung nodules as being positive in individual cases that had a negative result in supine position PET/CT.

Polycyclic aromatic hydrocarbons (PAHs) in indoor environments are still imposing carcinogenic risk.

Polycyclic aromatic hydrocarbons (PAHs) are among the most health-relevant air pollutants. Herein, we conducted meta-analysis and experimental validation to evaluate PAHs in our surroundings and carcinogenic risks. We summarized the occurrence of PAHs in outdoors and indoors from 131 studies with 6,766 samples collected in different countries in 1989-2019. The global weighted-median concentration in outdoor air, indoor air and dust of ΣPAHs were 142 ng/m3, 369 ng/m3 and 10,201 ng/g; respectively. ΣPAHs have decreased in indoor air but remained steady in outdoor air and indoor dust. More carcinogenic PAHs in indoor/outdoor air was observed in Asia, while in dust was North America. Monte-Carlo simulation further showed indoor sources for children's exposure from dust and air can exceed outdoor. To further validate the health effect of PAHs from indoors, 15 more recent indoor dust samples were collected to examine their mutagenicity. The results showed that ΣPAHs were found to be significantly correlated with mutagenicity potency in the dust sample metabolically activated with liver S9 subcellular fraction and likely accounted for 0.42-0.50 of the mutagenic activity. Our findings indicated that PAHs are still likely to have carcinogenic activity in indoor environments and exposure risk of children to indoor dust should be emphasized.

Clinicopathological characteristics of primary central nervous system lymphoma with low 18F-fludeoxyglucose uptake on brain positron emission tomography.

Primary central nervous system lymphoma (PCNSL) typically shows a strong uptake of F-fludeoxyglucose (FDG) imaged by positron emission tomography (PET). Uncommonly, PCNSL demonstrates a low uptake on FDG PET. We investigated the clinicopathological characteristics of the unusual cases of PCNSL with low FDG uptake.We retrospectively enrolled 104 consecutive patients with newly diagnosed PCNSL who underwent baseline brain FDG PET. The degree of FDG uptake of PCNSL was visually scored by 4 grades (0, ≤contralateral white matter; 1, >contralateral white matter and contralateral gray matter). Grades 0-2 were considered as PCNSL with low uptake. We investigated association of low uptake of PCNSL with the following clinicopathological factors: age, sex, steroid treatment, lactate dehydrogenase level, cerebrospinal fluid protein level, condition of PET scanning, immunohistochemical markers (cluster of differentiation 10 [CD10], B-cell lymphoma 6 [BCL-6], B-cell lymphoma 2 [BCL-2], multiple myeloma oncogene 1 [MUM1], Epstein-Barr virus [EBV] protein, and Ki67), location of lesions, tumor size, multiplicity of lesions, involvement of deep brain structures, and cystic or necrotic appearance of lesions.Of the 104 patients with PCNSL, 14 patients (13.5%) showed PCNSL with low FDG uptake on PET. Among various clinicopathological factors, MUM1 negativity was the only factor associated with low FDG uptake PCNSL by univariate (P = .002) and multivariate analysis (P = .007).This study suggests that the different clinicopathological characteristics between patients with high uptake and low uptake of PCNSL on FDG PET is closely associated with lack of MUM1, a protein known to be a crucial regulator of B-cell development and tumorigenesis.

Is dual-phase SPECT/CT with 99mTc-sestamibi better than single-phase SPECT/CT for lesion localization in patients with hyperparathyroidism?

This study aimed to establish an optimal protocol for Tc-sestamibi parathyroid imaging for lesion localization in patients with hyperparathyroidism (HPT).We retrospectively enrolled 35 consecutive patients who underwent dual-phase (at 10 minutes and 120 minutes) Tc-sestamibi parathyroid scintigraphy with single-photon emission computed tomography (SPECT)/computed tomography (CT). Twenty seven patients had primary HPT, and 8 had secondary or tertiary HPT. Three nuclear medicine physicians independently analyzed the parathyroid images for lesion localization at 9 predefined parathyroid locations using the following 4 different image sets blinded to the clinical information:All SPECT or SPECT/CT image sets were analyzed with dual-phase planar images. The image results were compared with the histopathological results after surgery.Dual-phase SPECT/CT showed the highest positive rate of 85.7% in the patient-based analysis and 13.7% in the location-based analysis. Of 35 patients, surgical pathological results were available in 21 (16 adenomas in 16 primary HPTs and 16 hyperplasias in 5 secondary or tertiary HPTs). Dual-phase SPECT/CT showed the sensitivity values of 100% and 84.4% in the patient-based and location-based analysis, respectively, which were the highest sensitivity values among all image sets. In the primary HPT subgroup, dual-phase SPECT/CT showed the highest sensitivity value of 93.8% in the location-based analyses, whereas dual-phase SPECT, early SPECT/CT, and delayed SPECT/CT showed the sensitivity values of 62.5%, 81.3%, and 81.3%, respectively. In the secondary or tertiary HPT subgroup, dual-phase SPECT/CT also showed the highest sensitivity value of 75.0%, whereas early SPECT/CT, delayed SPECT/CT, and dual-phase SPECT showed the sensitivity values of 43.8%, 56.3%, and 68.8%, respectively.Compared with dual-phase SPECT or single-phase SPECT/CT, the dual-phase SPECT/CT imaging protocol for Tc-sestamibi scintigraphy showed the highest positive rate and sensitivity, and was optimal for parathyroid lesion localization.

Feasibility of real-time in vivo 89Zr-DFO-labeled CAR T-cell trafficking using PET imaging.

INTRODUCTION: Chimeric antigen receptor (CAR) T-cells have been recently developed and are producing impressive outcomes in patients with hematologic malignancies. However, there is no standardized method for cell trafficking and in vivo CAR T-cell monitoring. We assessed the feasibility of real-time in vivo 89Zr-p-Isothiocyanatobenzyl-desferrioxamine (Df-Bz-NCS, DFO) labeled CAR T-cell trafficking using positron emission tomography (PET). RESULTS: The 89Zr-DFO radiolabeling efficiency of Jurkat/CAR and human peripheral blood mononuclear cells (hPBMC)/CAR T-cells was 70%-79%, and cell radiolabeling activity was 98.1-103.6 kBq/106 cells. Cell viability after radiolabeling was >95%. Cell proliferation was not significantly different during the early period after radiolabeling, compared with unlabeled cells; however, the proliferative capacity decreased over time (day 7 after labeling). IL-2 or IFN-γ secretion was not significantly different between unlabeled and labeled CAR T-cells. PET/magnetic resonance imaging in the xenograft model showed that most of the 89Zr-DFO-labeled Jurkat/CAR T-cells were distributed in the lung (24.4% ± 3.4%ID) and liver (22.9% ± 5.6%ID) by one hour after injection. The cells gradually migrated from the lung to the liver and spleen by day 1, and remained stable in these sites until day 7 (on day 7: lung 3.9% ± 0.3%ID, liver 36.4% ± 2.7%ID, spleen 1.4% ± 0.3%ID). No significant accumulation of labeled cells was identified in tumors. A similar pattern was observed in ex vivo biodistributions on day 7 (lung 3.0% ± 1.0%ID, liver 19.8% ± 2.2%ID, spleen 2.3% ± 1.7%ID). 89Zr-DFO-labeled hPBMC/CAR T-cells showed a similar distribution, compared with Jurkat/CAR T-cells, on serial PET images. CAR T cell distribution was cross-confirmed by flow cytometry, Alu polymerase chain reaction, and immunohistochemistry. CONCLUSION: Real-time in vivo cell trafficking is feasible using PET imaging of 89Zr-DFO-labeled CAR T-cells. This can be used to investigate cellular kinetics, initial in vivo biodistribution, and safety profiles in future CAR T-cell development.

Diagnostic accuracy and safety of 16α-[18F]fluoro-17ß-oestradiol PET-CT for the assessment of oestrogen receptor status in recurrent or metastatic lesions in patients with breast cancer: a prospective cohort study.

BACKGROUND: A biopsy of first recurrence or metastatic disease is recommended to re-evaluate oestrogen receptor status in patients with breast cancer and to select appropriate treatment. However, retesting for oestrogen receptor status with rebiopsy is not always feasible, depending on lesion location and the risk associated with biopsy, and in these cases clinicians continue to treat patients according to the oestrogen receptor status of the primary tumour. Consequently suboptimal therapy might be offered to these patients. We assessed the diagnostic accuracy and safety of 16α-[18F]fluoro-17ß-oestradiol (18F-FES) PET-CT to assess oestrogen receptor status in patients with recurrent or metastatic breast cancer. METHODS: We did a prospective cohort study at the Asan Medical Center, Seoul, South Korea. Eligible patients had breast cancer, with first recurrence or metastatic disease at presentation, were 19 years or older, and had an Eastern Cooperative Oncology Group performance status of 0-2. The primary objective was to show the agreement between qualitative 18F-FES PET-CT interpretation and the results of oestrogen receptor expression by immunohistochemical assay, a non-reference standard test. Whole-body 18F-FES PET-CT imaging was done after intravenous injection of 111-222 MBq of 18F-FES, with dosing primarily determined by radiation dosimetry analysis. 18F-FES uptake above background intensity was interpreted as positive. Efficacy was assessed in all patients with histologically confirmed recurrent or metastatic breast cancer who received 18F-FES and had PET-CT images available (intention-to-diagnose analysis), and safety was assessed in all patients who received 18F-FES. This study is registered with ClinicalTrials.gov, number NCT01986569. FINDINGS: Between Nov 27, 2013, and Nov 10, 2016, 93 patients were enrolled. Of the 85 patients included in the efficacy analysis, 47 (55%) were oestrogen receptor-positive and 38 (45%) were oestrogen receptor-negative. Positive status percent agreement between the 18F-FES PET-CT results and oestrogen receptor status by immunohistochemical assay was 76·6% (95% CI 62·0-87·7) and the negative status percent agreement was 100·0% (90·8-100·0). Patients who were oestrogen receptor-positive and had a positive 18F-FES PET-CT result had a significantly higher progesterone receptor expression than those who were oestrogen receptor-positive and had a negative 18F-FES PET-CT result (23 [68%] of 34 patients vs 0 of 11 patients; p<0·0001). The most common adverse event was procedural pain in nine (10%) of 90 patients injected with 18F-FES. No adverse events were related to the study drug except injection site pain in one (1%) patient. No serious adverse events were recorded. INTERPRETATION: The high negative percent agreement between 18F-FES PET-CT and oestrogen receptor status by immunohistochemical assay in this cohort suggests that positive 18F-FES uptake by recurrent or metastatic oestrogen receptor-positive breast cancer lesions could be an alternative to oestrogen receptor assays in this setting. Staging assessment should include 18F-FES PET-CT when retesting oestrogen receptor status is not feasible. FUNDING: Asan Institute for Life Sciences, Ministry of Health and Welfare, South Korea.

The Prognostic Value of 18F-FDG Uptake in the Supraclavicular Lymph Node (N3c) on PET/CT in Patients With Locally Advanced Breast Cancer With Clinical N3c.

PURPOSE: We investigated the prognostic value of F-FDG uptake in the supraclavicular lymph node (SCLN) on PET/CT in breast cancer patients with clinical ipsilateral SCLN metastasis (cN3c). METHODS: Fifty-five female patients with initial F-FDG PET/CT were treated with curative intent. For semiquantitative analysis, the SUVmax of the primary tumor, axillary lymph node, and SCLN were normalized by the SUVmean of the liver (defined as SUVR-tumor, SUVR-axillary lymph node, and SUVR-SCLN, respectively). Cox proportional hazards models were used to predict disease-free survival (DFS) and overall survival (OS). Differences in DFS and OS were assessed by Kaplan-Meier analysis. RESULTS: Twenty-three patients (41.8%) experienced recurrence, and 13 (23.6%) died during follow-up (median, 70.0 months; range, 6-128 months). In multivariate analysis, SUVR-tumor greater than 3.26 (hazards ratio, 7.26; 95% confidence interval, 1.58-33.31; P = 0.01) and SUVR-SCLN greater than 1.05 (hazards ratio, 8.47; 95% confidence interval, 1.09-65.87; P = 0.04) were prognostic for OS. No clinicopathologic or PET/CT parameters were prognostic for DFS. The patients were divided into 3 groups: group 1 (n = 11, SUVR-tumor ≤3.26 and SUVR-SCLN ≤1.05); group 2 (n = 27, SUVR-tumor >3.26 or SUVR-SCLN >1.05); and group 3 (n = 17, SUVR-tumor >3.26 and SUVR-SCLN >1.05). The 5-year OS rates were 100% in group 1, 85.2% in group 2, and 51.0% in group 3. Group 3 showed worse prognosis than group 1 (P < 0.01) and group 2 (P < 0.01). CONCLUSIONS: In addition to SUVR-tumor, SUVR-SCLN seemed to play an important role in selecting patients with the worst prognosis.

Is 18F-FDG PET/CT useful for the differential diagnosis of solitary pulmonary nodules in patients with idiopathic pulmonary fibrosis?

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is associated with an increased incidence of lung cancer, but patients with IPF often have poor pulmonary function and are vulnerable to pneumothorax and so using an invasive procedure to diagnose a single nodule detected on chest CT risks a critical adverse outcome. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is recognized to be useful for differentiating between benign and malignant solitary pulmonary nodules (SPN) in patients without IPF, but its diagnostic accuracy has not been investigated in patients with IPF. In this study, therefore, we investigated whether 18F-FDG PET/CT is useful for the differential diagnosis of SPNs in patients with IPF. METHODS: From the IPF patient cohort of our institution, we retrospectively reviewed 55 patients (54 men, 1 woman; age 67.8 ± 7.6 years) with an SPN sized 8-30 mm (mean 18.5 ± 5.7 mm) who underwent chest CT followed by 18F-FDG PET/CT between April 2004 and March 2016. The 18F-FDG uptake of the SPN was analyzed visually and semiquantitatively, and these determinations were compared with the final diagnosis obtained by pathology (n = 52) or imaging follow-up (n = 3). RESULTS: The final diagnoses showed that 41 (75%) of the SPNs were malignant (21 squamous cell carcinomas, 9 adenocarcinomas, 5 small-cell carcinomas, 4 mixed-type carcinomas, 1 large-cell neuroendocrine carcinoma, and 1 sarcoid carcinoma) and 14 (25%) were benign. The determination of malignant SPNs by visual analysis of the PET/CT images had a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 98, 86, 95, and 92%, respectively. The semiquantitative analysis using a maximum standardized uptake value of 2.0 as the cut-off had a sensitivity, specificity, PPV, and NPV of 95, 93, 98, and 87%, respectively. CONCLUSIONS: 18F-FDG PET/CT is useful for differentiating benign and malignant SPNs in patients with IPF, as it is for patients without IPF.

Association Between (18)F-FDG Avidity and the BRAF Mutation in Papillary Thyroid Carcinoma.

PURPOSE: The BRAF mutation, a potential prognostic factor in papillary thyroid carcinoma (PTC), is associated with a high expression of the glucose transporter gene. We investigated which clinicopathologic factors, including BRAF mutation status, influence (18)F-fluoro-2-deoxyglucose ((18)F-FDG) avidity. METHODS: We retrospectively reviewed 55 patients who underwent BRAF analysis from biopsy-confirmed PTC and (18)F-FDG positron emission tomography/computed tomography within 6 months before undergoing thyroid surgery from September 2008 to August 2014. Tumors were considered to be (18)F-FDG avid if the uptake was greater than that of the liver. (18)F-FDG uptake of PTCs was also analyzed semiquantitatively using SUVmax. The association between (18)F-FDG avidity and clinicopathologic variables (age, tumor size, perithyroidal extension, cervical lymph node status, and BRAF mutation status) was investigated. RESULTS: Twenty-nine (52.7 %) of 55 patients had (18)F-FDG-avid PTCs. PTCs with the BRAF mutation showed higher (18)F-FDG avidity (24/38, 63.2 %) than those without (5/17, 29.4 %). The BRAF mutation (p = 0.025) and tumor size (p = 0.003) were significantly associated with (18)F-FDG avidity in univariate analysis, and the BRAF mutation status remained significant after adjusting for tumor size in multivariate analysis (p = 0.015). In the subgroup of tumor size ≥ 1 cm, the BRAF mutation was the only factor significantly associated with (18)F-FDG avidity (p = 0.021). The mean SUVmax of PTCs with the BRAF mutation was significantly higher than that of those without (4.89 ± 6.12 vs. 1.96 ± 1.10, p = 0.039). CONCLUSIONS: The BRAF mutation must be one of the most important factors influencing (18)F-FDG avidity in PTCs, especially in those with a tumor size ≥ 1 cm.

Performance of (18)F-FDG PET/CT as a postoperative surveillance imaging modality for asymptomatic advanced gastric cancer patients.

OBJECTIVE: The purpose of this study was to investigate the diagnostic performance of postoperative fluorine-18 fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) as a surveillance modality for advanced gastric cancer patients who were asymptomatic and negative by conventional follow-up. METHODS: We retrospectively collected 46 advanced gastric cancer patients who received approximately 1-year-postoperative (18)F-FDG PET/CT surveillance following curative resection (mean age 60.6 ± 11.5 years). (18)F-FDG PET/CT was interpreted by nuclear medicine physicians who were blind to the clinical information. Final confirmation was determined by clinical follow-up using tumor markers, conventional CT scan, upper gastrointestinal endoscopy and with/without subsequent histopathologic diagnosis. RESULTS: Four patients developed recurrence (8.7 %; 1 local and 3 distant recurrences). For local recurrence, (18)F-FDG PET/CT found four hypermetabolic lesions and one was local recurrence. For distant recurrence, seven hypermetabolic lesions were found in six patients and true-positive was three lesions. False-positive cases were mainly turned out to be physiologic small bowel uptake. Regardless of the recurrence site, the sensitivity, specificity, positive predictive value and negative predictive value of (18)F-FDG PET/CT were 100 % (4/4, 95 % confidence interval (CI) 39.6-100 %), 88.1 % (37/42, 95 % CI 73.6-95.5 %), 44.4 % (4/9, 95 % CI 15.3-77.3 %) and 100 % (37/37, 95 % CI 88.3-100 %), respectively in the patient-based analysis. CONCLUSION: Our study showed good specificity of postoperative surveillance (18)F-FDG PET/CT for detecting recurrence. Careful caution should be made for interpreting some false-positive hypermetabolic lesions in postoperative (18)F-FDG PET/CT, especially at the local anastomosis site.