PSMA and FDG PET/CT Findings in Patient With Dedifferentiated Liposarcoma and Prostate Cancer Metastases.

ABSTRACT: Dedifferentiated liposarcoma is an extremely rare and highly malignant tumor. We demonstrated a case of a 75-year-old man with significantly PSMA-avid and mildly FDG uptake-dedifferentiated liposarcoma in the retroperitoneal area. The double-tracer (PSMA and FDG) PET scans could further contribute to differential diagnosis and the following treatment strategy for patients who were suspected with prostate cancer metastases and other malignant tumors simultaneously.

The value on SUV-derived parameters assessed on 18F-FDG PET/CT for predicting mediastinal lymph node metastasis in non-small cell lung cancer.

PURPOSE: To explore valuable predictors for mediastinal lymph node metastasis in non-small cell lung cancer (NSCLC) patients, we analyzed the potential roles of standardized uptake value (SUV)-derived parameters from preoperative 18F-FDG PET/CT combined with clinical characteristics. METHODS: Data from 224 NSCLC patients who underwent preoperative 18F-FDG PET/CT scans in our hospital were collected. Then, a series of clinical parameters including SUV-derived features [SUVmax of mediastinal lymph node and primary-tumor SUVmax, SUVpeak, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG)] were evaluated. The best possible cutoff points for all measuring parameters were calculated using receiver operating characteristic curve (ROC) analysis. Predictive analyses were performed using a Logistic regression model to determine the predictive factors for mediastinal lymph node metastasis in NSCLC and lung adenocarcinoma patients. After multivariate model construction, data of another 100 NSCLC patients were recorded. Then, 224 patients and 100 patients were enrolled to validate the predictive model by the area under the receiver operating characteristic curve (AUC). RESULTS: The mediastinal lymph node metastasis rates in 224 patients for model construction and 100 patients for model validation were 24.1% (54/224) and 25% (25/100), respectively. It was found that SUVmax of mediastinal lymph node ≥ 2.49, primary-tumor SUVmax ≥ 4.11, primary-tumor SUVpeak ≥ 2.92, primary-tumor SUVmean ≥ 2.39, primary-tumor MTV ≥ 30.88 cm3, and primary-tumor TLG ≥ 83.53 were more prone to mediastinal lymph node metastasis through univariate logistic regression analyses. The multivariate logistic regression analyses showed that the SUVmax of mediastinal lymph nodes (≥ 2.49: OR 7.215, 95% CI 3.326-15.649), primary-tumor SUVpeak (≥ 2.92: OR 5.717, 95% CI 2.094-15.605), CEA (≥ 3.94 ng/ml: OR 2.467, 95% CI 1.182-5.149), and SCC (< 1.15 ng/ml: OR 4.795, 95% CI 2.019-11.388) were independent predictive factors for lymph node metastasis in the mediastinum. It was found that SUVmax of the mediastinal lymph node (≥ 2.49: OR 8.067, 95% CI 3.193-20.383), primary-tumor SUVpeak (≥ 2.92: OR 9.219, 95% CI 3.096-27.452), and CA19-9 (≥ 16.6 U/ml: OR 3.750, 95% CI 1.485-9.470) were significant predictive factors for mediastinal lymph node metastasis in lung adenocarcinoma patients. The AUCs for the predictive value of the NSCLC multivariate model through internal and external validation were 0.833 (95% CI 0.769- 0.896) and 0.811 (95% CI 0.712-0.911), respectively. CONCLUSION: High SUV-derived parameters (SUVmax of mediastinal lymph node and primary-tumor SUVmax, SUVpeak, SUVmean, MTV and TLG) might provide varying degrees of predictive value for mediastinal lymph node metastasis in NSCLC patients. In particular, the SUVmax of mediastinal lymph nodes and primary-tumor SUVpeak could be independently and significantly associated with mediastinal lymph node metastasis in NSCLC and lung adenocarcinoma patients. Internal and external validation confirmed that the pretherapeutic SUVmax of the mediastinal lymph node and primary-tumor SUVpeak combined with serum CEA and SCC can effectively predict mediastinal lymph node metastasis of NSCLC patients.

PET/CT molecular imaging in the era of immune-checkpoint inhibitors therapy.

Cancer immunotherapy, especially immune-checkpoint inhibitors (ICIs), has paved a new way for the treatment of many types of malignancies, particularly advanced-stage cancers. Accumulating evidence suggests that as a molecular imaging modality, positron emission tomography/computed tomography (PET/CT) can play a vital role in the management of ICIs therapy by using different molecular probes and metabolic parameters. In this review, we will provide a comprehensive overview of the clinical data to support the importance of 18F-fluorodeoxyglucose PET/CT (18F-FDG PET/CT) imaging in the treatment of ICIs, including the evaluation of the tumor microenvironment, discovery of immune-related adverse events, evaluation of therapeutic efficacy, and prediction of therapeutic prognosis. We also discuss perspectives on the development direction of 18F-FDG PET/CT imaging, with a particular emphasis on possible challenges in the future. In addition, we summarize the researches on novel PET molecular probes that are expected to potentially promote the precise application of ICIs.

Diagnostic performance and prognostic value of preoperative 18F-FDG PET/CT in renal cell carcinoma patients with venous tumor thrombus.

BACKGROUND: To observe the diagnostic efficacy of preoperative fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) upon venous tumor thrombus (VTT) in patients with renal cell carcinoma (RCC), and investigate the prognostic value of imaging parameters integrated with clinicopathological characteristics in patients with VTT after nephrectomy with tumor thrombectomy. METHODS: Patients with newly diagnosed RCC who underwent 18F-FDG PET/CT were reviewed retrospectively. The diagnostic efficacy of 18F-FDG PET/CT in VTT was analyzed. Logistic regression analysis was carried out to identify the clinical variables and PET/CT variables (including maximum standardized uptake value (SUVmax) of primary tumor, VTT SUVmax and primary tumor size) for differentiating early VTT (Mayo 0-II) from advanced VTT (Mayo III-IV). Cox proportional hazard analyses were used to evaluate clinicopathological factors and PET/CT factors (including distant metastasis, primary tumor SUVmax, VTT SUVmax and primary tumor size) for disease-free survival (DFS) in patients with VTT after operation. RESULTS: A total of 174 eligible patients were included in this study, including 114 men (65.5%) and 60 women (34.5%), with a median age of 58 years (range, 16-81 years). The distribution of pathological tumor stage (T stage) was 56 (T1), 17 (T2), 95 (T3), and 6 cases (T4), respectively. According to WHO/ISUP grade, except for 4 cases of chromophobe cell RCC, there were 14 patients (8.0%) of grade 1, 59 patients (33.9%) of grade 2, 74 patients (42.5%) of grade 3 and 23 patients (13.2%) of grade 4. The median maximum diameter of the primary tumor on PET/CT was 7.3 cm (5.0-9.5 cm). The distal metastasis was observed in 46 patients (26.4%). Sixty-one cases (35.1%) were confirmed with VTT by pathology. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 18F-FDG PET/CT imaging were 96.7, 99.1, 98.3, 98.3, and 98.2%, in detecting VTT, respectively, and 70.0, 100.0, 94.9, 100.0, and 94.2%, in evaluating the level of VTT, respectively. Elevated VTT SUVmax (≥5.20) could significantly distinguish the early VTT group and advanced VTT group (P = 0.010). In the prognosis analysis, elevated VTT SUVmax (≥4.30) (P = 0.018, HR 3.123, 95% CI 1.212-8.044) and distant metastasis (P = 0.013, HR 3.344, 95% CI 1.293-8.649) were significantly independent predictors for DFS. CONCLUSION: Preoperative 18F-FDG PET/CT has a high diagnostic efficacy in detecting VTT and evaluating its level in RCC patients. Those patients with elevated VTT SUVmax should be carefully monitored to detect the possibility of disease progression after operation.

Potentials of Non-Invasive 18F-FDG PET/CT in Immunotherapy Prediction for Non-Small Cell Lung Cancer.

The immune checkpoint inhibitors (ICIs), by targeting cytotoxic-T-lymphocyte-associated protein 4, programmed cell death 1 (PD-1), or PD-ligand 1, have dramatically changed the natural history of several cancers, including non-small cell lung cancer (NSCLC). There are unusual response manifestations (such as pseudo-progression, hyper-progression, and immune-related adverse events) observed in patients with ICIs because of the unique mechanisms of these agents. These specific situations challenge response and prognostic assessment to ICIs challenging. This review demonstrates how 18F-FDG PET/CT can help identify these unusual response patterns in a non-invasive and effective way. Then, a series of semi-quantitative parameters derived from 18F-FDG PET/CT are introduced. These indexes have been recognized as the non-invasive biomarkers to predicting the efficacy of ICIs and survival of NSCLC patients according to the latest clinical studies. Moreover, the current situation regarding the functional criteria based on 18F-FDG PET/CT for immunotherapeutic response assessment is presented and analyzed. Although the criteria based on 18F-FDG PET/CT proposed some resolutions to overcome limitations of morphologic criteria in the assessment of tumor response to ICIs, further researches should be performed to validate and improve these assessing systems. Then, the last part in this review displays the present status and a perspective of novel specific PET probes targeting key molecules relevant to immunotherapy in prediction and response assessment.

2-[18F]FDG PET/CT parameters associated with WHO/ISUP grade in clear cell renal cell carcinoma.

PURPOSE: To explore the potential parameters from preoperative 2-[18F]FDG PET/CT that might associate with the World Health Organization/the International Society of Urological Pathology (WHO/ISUP) grade in clear cell renal cell carcinoma (ccRCC). METHODS: One hundred twenty-five patients with newly diagnosed ccRCC who underwent 2-[18F]FDG PET/CT prior to surgery or biopsy were retrospectively reviewed. The metabolic parameters and imaging features obtained from 2-[18F]FDG PET/CT examinations were analyzed in combination with clinical characteristics. Univariate and multivariate logistic regression analyses were performed to identify the predictive factors of WHO/ISUP grade. RESULTS: Metabolic parameters of primary tumor maximum standardized uptake value (SUVmax), tumor-to-liver SUV ratio (TLR), and tumor-to-kidney SUV ratio (TKR) were significantly different between any two of the four different WHO/ISUP grades, except those between the WHO/ISUP grade 3 and grade 4. The optimal cutoff values to predict high WHO/ISUP grade for SUVmax, TLR, and TKR were 4.15, 1.63, and 1.59, respectively. TLR (AUC: 0.841) was superior to TKR (AUC: 0.810) in distinguishing high and low WHO/ISUP grades (P = 0.0042). In univariate analysis, SUVmax, TLR, TKR, primary tumor size, tumor thrombus, distant metastases, and clinical symptoms could discriminate between the high and low WHO/ISUP grades (P < 0.05). In multivariate analysis, TLR (P < 0.001; OR: 1.732; 95%CI: 1.289-2.328) and tumor thrombus (P < 0.001; OR: 6.199; 95%CI: 2.499-15.375) were significant factors for differentiating WHO/ISUP grades. CONCLUSION: Elevated TLR (> 1.63) and presence of tumor thrombus from preoperative 2-[18F]FDG PET/CT can distinguish high WHO/ISUP grade ccRCC effectively. 2-[18F]FDG PET/CT may be a feasible method for noninvasive assessment of WHO/ISUP grade.

Elevated tumor-to-liver standardized uptake value ratio (TLR) from preoperative 18F-FDG PET/CT predicts poor prognosis of patients with clear cell renal cell carcinoma after nephrectomy.

AIM: To assess the potential of using preoperative 18F-FDG PET/CT to predict the prognosis of patients with clear cell renal cell carcinoma (ccRCC) after nephrectomy. METHODS: Sixty-nine patients with newly diagnosed ccRCC who underwent 18F-FDG PET/CT prior to surgery were retrospectively reviewed. The metabolic parameters of maximum standardized uptake value (SUVmax) and tumor-to-liver ratio (TLR) from 18F-FDG PET/CT were obtained. Clinicopathological characteristics, including the World Health Organization/the International Society of Urological Pathology (WHO/ISUP) grade, pathological tumor node metastasis (pTNM) stage, venous tumor thrombus, and so on, were acquired. Univariate and multivariate Cox proportional hazards analyses were performed to identify the prognostic factors for disease-free survival (DFS). RESULTS: Of the 69 patients, 25 patients (36.2%) experienced disease progression during the follow-up period. In univariate analysis, the primary tumor size (>4.85 cm), pTNM stage (Ⅲ/Ⅳ), WHO/ISUP grade (G3/4), venous tumor thrombus, adjuvant therapy, SUVmax (>3.55), and TLR (>1.66) were found to correlate with the incidence of decreased DFS (P < 0.05). In multivariate analysis, TLR (P = 0.007, HR: 5.489, 95%CI: 1.605-18.774) and pTNM stage (P = 0.024, HR: 10.385, 95%CI: 1.361-79.238) were revealed to serve as independent prognostic predictors for DFS after adjustment for other variables. Only 3 cases (8.3%) with normal TLR showed disease progression, while 22 cases (66.7%) with elevated TLR experienced disease progression. CONCLUSION: ccRCC patients with preoperatively elevated TLR (>1.66) and high pTNM stages (Ⅲ/Ⅳ) had significantly unfavorable survival outcomes. These patients should be carefully monitored to detect the possibility of disease progression after nephrectomy as early as possible.

Primary metabolic tumor volume from 18F-FDG PET/CT associated with epidermal growth factor receptor mutation in lung adenocarcinoma patients.

PURPOSE: To explore the potential parameters from F-FDG PET/CT that might be associated with the epidermal growth factor receptor (EGFR) gene mutation status in lung adenocarcinoma (ADC) patients. METHODS: Data of the test cohort of 191 patients and the validation cohort of 55 patients with newly diagnosed ADC were retrospectively reviewed. All patients underwent F-FDG PET/CT scans and EGFR mutation tests prior to treatment. The metabolic parameters obtained from F-FDG PET/CT combining with clinical characteristics were analyzed by using univariate and multivariate logistic regression analyses. Then two cohorts were enrolled to validate the predictive model by area under the receiver-operating characteristic curve (AUC), respectively. RESULTS: EGFR mutation-positive was seen of 33.0% (63/191) and 32.7% (18/55) in two cohorts, respectively. In univariate analysis, female, nonsmokers, metabolic parameters of primary tumor [mean standardized uptake value, metabolic tumor volume (pMTV), and total lesion glycolysis], non-necrosis of primary tumor, and serum tumor markers [carbohydrate antigen 19-9, squamous cell carcinoma antigen, and precursor of gastrin releasing peptide (proGRP)] were significantly relevant with EGFR mutation. In multivariate analysis with adjustment of age and TNM stage, pMTV (<8.13 cm), proGRP (≥38.44 pg/ml) and women were independent significant predictors for EGFR mutation. The AUC for the predictive value of these factors was 0.739 [95% confidence interval (CI) 0.665-0.813] in the cohort of 191 patients and 0.716 (95% CI 0.567-0.865) in the cohort of 55 patients, respectively. CONCLUSION: Low pMTV (<8.13 cm) was an independent predictor and could be integrated with women and high proGRP (≥38.44 pg/ml) to enhance the discriminability on the EGFR mutation status in ADC patients.

Noninvasive PET Imaging of a Ga-68-Radiolabeled RRL-Derived Peptide in Hepatocarcinoma Murine Models.

PURPOSE: Tc-99m- and I-131-labeled arginine-arginine-leucine (RRL) peptides have shown the feasibility of tumor imaging in our previous studies. However, there have been no reports using RRL peptide for positron emission tomography (PET) imaging. In this study, RRL was radiolabeled with Ga-68 under optimized reaction conditions to develop a better specific and effective tumor imaging agent. PROCEDURES: RRL was synthesized and conjugated to a bifunctional chelating agent (DOTA-NHS), then radiolabeled with Ga-68. Labeling yield was optimized by varying pH, temperature, and reaction time and the stability was evaluated in human fresh serum. Cellular uptakes of [68Ga]DOTA-RRL and FITC-conjugated RRL in HepG2 cells were evaluated using a gamma counter, confocal microscopy, and flow cytometry. PET images and biodistribution were performed in HepG2 tumor-bearing mice after injection of [68Ga]DOTA-RRL or [68Ga]GaCl3 at different time points. Further, blocking study was investigated using cold RRL. RESULTS: The labeling yield of [68Ga]DOTA-RRL was 80.6 ± 3.9 % with a pH of 3.5-4.5 at 100 °C for 15 min. The cellular uptake of [68Ga]DOTA-RRL in HepG2 cells was significantly higher than that of [68Ga]GaCl3 (P < 0.05). Moreover, the high fluorescent affinity of FITC-conjugated RRL in HepG2 cells was shown using confocal microscopy and flow cytometry. After injection of [68Ga]DOTA-RRL in HepG2 tumor-bearing mice, tumor regions exhibited high radioactive accumulation over 120 min and the highest uptake at 30 min. After blocked with cold RRL, HepG2 tumors could not be visualized. [68Ga]GaCl3 was unable to show tumor images at any time point. The biodistribution results confirmed the PET imaging and blocking results. CONCLUSIONS: Our study successfully prepared [68Ga]DOTA-RRL with a high labeling yield under the optimized reaction conditions and demonstrated its potential role as a PET imaging agent for tumor-targeted diagnosis.

Radioimmunoimaging and targeting treatment in an immunocompetent murine model of triple-negative breast cancer using radiolabeled anti-programmed death-ligand 1 monoclonal antibody.

The overall aim of this study was to evaluate whether iodine-131 radiolabeled monoclonal antibody (mAb) targeting programmed death-ligand 1 (PD-L1) can be used for imaging of PD-L1 expression noninvasively in vivo and playing synergistic effect combined with immunotherapy. Anti-PD-L1 mAb was radiolabeled with iodine-131 (131 I-PD-L1 mAb) and was characterized in vitro. Biodistribution and imaging in vivo were performed periodically. Therapy study was conducted in triple-negative breast cancer-bearing BALB/c mice. As results, the labeling efficiencies of 131 I-PD-L1 mAb reached 80% ± 3%, with radiochemical purity of 97% ± 1%. 131 I-PD-L1 mAb preserved the capacity to bind living PD-L1-expressing cells specifically in vitro. Tumor radioactivity uptake of 131 I-PD-L1 mAb was significantly higher than that of control groups. The xenografts were clearly imaged from 48 to 72 hours noninvasively after injection of 131 I-PD-L1 mAb, while the xenografts were not imaged in control groups. Tumor growth was significantly inhibited, and median survival time was remarkably prolonged in combination therapy group compared with control groups. It was concluded that 131 I-PD-L1 mAb can be a potential theranostic candidate for visualizing of PD-L1 expression noninvasively and performing synergistic therapy in carcinomas.

[Metabolic activity measured by ¹8F-FDG PET/CT in newly diagnosed patients with non-Hodgkin lymphoma: correlation with immunophenotype].

OBJECTIVE: To compare the metabolic activity by ¹8F-fluorodeoxyglucose (¹8F-FDG) uptake across the various histologic subtypes of non-Hodgkin lymphoma (NHL) and to investigate the relationship between metabolic activity and immunophenotype. METHODS: Positron emission tomography/computed tomography (PET/CT) studies of patients with newly diagnosed NHL from Jul 2010 to Mar 2012 were retrospectively reviewed, 82 patients were enrolled in our study according to the inclusion and exclusion criteria. The maximum standardized uptake value (SUVmax) of each patient reflecting the metabolic activity was recorded. Mean SUVmax of aggressive B-cell NHL, indolent B-cell NHL and T-cell NHL were compared. Pearson and Spearman test were used to analyze the relationship between SUVmax and immunophenotype. RESULTS: The SUVmax of various subtypes of lymphoma revealed a wide range from 0.9 to 40.3, but lesions of 79 patients in this study showed obviously FDG uptake. SUVmax of indolent B-cell NHL (4.5 ± 2.4) was significantly lower than that of aggressive B-cell NHL (13.1 ± 7.6) (P = 0.000), T-cell NHL (8.0 ± 3.8) (P = 0.03). SUVmax of aggressive B-cell NHL was significantly higher than that of indolent B-cell NHL, T-cell NHL (P = 0.000, P = 0.005). SUVmax of B-cell NHL had positive correlation with Ki-67 expression (r = 0.493, P = 0.001) and negative correlation with CD138 (r = -0.654, P = 0.008). While SUVmax of T-cell NHL had no correlation with Ki-67 expression (P = 0.213), but had negative correlation with CD56 (r = -0.545, P = 0.044). CONCLUSIONS: Different subtype of NHL manifests markedly different intensity of FDG uptake, but most lesions of lymphoma are FDG avid. Metabolic activity is lower in indolent B-cell NHL than in aggressive B-cell NHL and T-cell lymphoma, which is concordant with its aggressiveness. SUVmax of B-cell NHL correlates with expression of Ki-67 and CD138. SUVmax of T-cell NHL is associated with the expression of CD56, no correlation is detected between SUVmax of T-cell NHL and Ki-67 proliferation.