Image-Based Analysis of Tumor Localization After Intra-Arterial Delivery of Technetium-99m-Labeled SPIO Using SPECT/CT and MRI.

The aim of this study is to evaluate the localization of 99mTc-labeled dextran-coated superparamagnetic iron oxide (SPIO) nanoparticles to the liver tumor using image-based analysis. We delivered 99mTc-SPIO intravenously or intra-arterially (IA) with/without Lipiodol to compare the tumor localization by gamma scintigraphy, single-photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) in a rabbit liver tumor. The gamma and SPECT image-based analysis shows that the uptake ratio of the tumor to the normal liver parenchyma is highest after delivery of 99mTc-SPIO with Lipiodol IA and that well correlates with the trend of the signal decrease in the liver MRIs. Intra-arterial delivery of SPIO with Lipiodol might be a good drug delivery system targeting the hepatic tumors, as confirmed by image-based analysis.

Usefulness of MRI-assisted metabolic volumetric parameters provided by simultaneous (18)F-fluorocholine PET/MRI for primary prostate cancer characterization.

PURPOSE: The aim of this study was to determine the usefulness of MRI-assisted positron emission tomography (PET) parameters provided by simultaneous (18)F-fluorocholine (FCH) PET/MRI for characterization of primary prostate cancer. METHODS: Thirty patients with localized prostate cancer (mean age 69.4 ± 6.7 years) confirmed by biopsy were prospectively enrolled for simultaneous PET/MRI imaging. The patients underwent (18)F-FCH PET/MRI 1 week before undergoing total prostatectomy. Multiple parameters of diffusion-weighted MRI [minimum and mean apparent diffusion coefficient (ADCmin and ADCmean)], metabolic PET [maximum and mean standardized uptake value (SUVmax and SUVmean)], and metabolic volumetric PET [metabolic tumor volume (MTV) and uptake volume product (UVP)] were compared with laboratory, pathologic, and immunohistochemical (IHC) features of the prostate cancer specimen. PET parameters were divided into two categories as follows: volume of interest (VOI) of prostate by SUV cutoff 2.5 (SUVmax, SUVmean, MTVSUV, and UVPSUV) and MRI-assisted VOI of prostate cancer (SUVmaxMRI, SUVmeanMRI, MTVMRI, and UVPMRI). RESULTS: The rates of prostate cancer-positive cases identified by MRI alone, (18)F-FCH PET alone, and (18)F-FCH PET/MRI were 83.3, 80.0, and 93.3%, respectively. Among the multiple PET/MRI parameters, MTVMRI showed fair correlation with serum prostate-specific antigen (PSA; r = 0.442, p = 0.014) and highest correlation with tumor volume (r = 0.953, p < 0.001). UVPMRI showed highest correlation with serum PSA (r = 0.531, p = 0.003), good correlation with tumor volume (r = 0.908, p < 0.001), and it was significantly associated with Gleason score (p = 0.041). High MTVMRI and UVPMRI values were significant for perineural invasion, lymphatic invasion, extracapsular extension, seminal vesicle invasion, and positive B-cell lymphoma 2 (Bcl-2) expression (all p < 0.05). CONCLUSION: Simultaneous (18)F-FCH PET/MRI demonstrated a better diagnostic value for localized prostate cancer detection than each individual modality. MRI-assisted metabolic volumetric PET parameters (MTVMRI and UVPMRI) provided more accurate characterization of prostate cancer than conventional PET and MRI parameters.

Imaging in Tumor Immunology.

Recent advances in immune modulation have made impressive progress in cancer immunotherapy. Because dynamic nature of the immune response often makes it difficult to evaluate therapeutic outcomes, innovative imaging technologies have been developed to enable non-invasive visualization of immune cells and tumors in their microenvironment. This review summarizes the current tumor immunology and describes new innovative imaging methods with great potential to obtain non-invasive real-time insights into the complex functions of the immune system and into the management of cancer immunotherapy.

[18F]CB251 PET/MR imaging probe targeting translocator protein (TSPO) independent of its Polymorphism in a Neuroinflammation Model.

The 18 kDa translocator protein (TSPO) has been proposed as a biomarker for the detection of neuroinflammation. Although various PET probes targeting TSPO have been developed, a highly selective probe for detecting TSPO is still needed because single nucleotide polymorphisms in the human TSPO gene greatly affect the binding affinity of TSPO ligands. Here, we describe the visualization of neuroinflammation with a multimodality imaging system using our recently developed TSPO-targeting radionuclide PET probe [18F]CB251, which is less affected by TSPO polymorphisms. Methods: To test the selectivity of [18F]CB251 for TSPO polymorphisms, 293FT cells expressing polymorphic TSPO were generated by introducing the coding sequences of wild-type (WT) and mutant (Alanine → Threonine at 147th Amino Acid; A147T) forms. Competitive inhibition assay was conducted with [3H]PK11195 and various TSPO ligands using membrane proteins isolated from 293FT cells expressing TSPO WT or mutant-A147T, representing high-affinity binder (HAB) or low-affinity binder (LAB), respectively. IC50 values of each ligand to [3H]PK11195 in HAB or LAB were measured and the ratio of IC50 values of each ligand to [3H]PK11195 in HAB to LAB was calculated, indicating the sensitivity of TSPO polymorphism. Cellular uptake of [18F]CB251 was measured with different TSPO polymorphisms, and phantom studies of [18F]CB251-PET using 293FT cells were performed. To test TSPO-specific cellular uptake of [18F]CB251, TSPO expression was regulated with pCMV-TSPO (or shTSPO)/eGFP vector. Intracranial lipopolysaccharide (LPS) treatment was used to induce regional inflammation in the mouse brain. Gadolinium (Gd)-DOTA MRI was used to monitor the disruption of the blood-brain barrier (BBB) and infiltration by immune cells. Infiltration of peripheral immune cells across the BBB, which exacerbates neuroinflammation to produce higher levels of neurotoxicity, was also monitored with bioluminescence imaging (BLI). Peripheral immune cells isolated from luciferase-expressing transgenic mice were transferred to syngeneic inflamed mice. Neuroinflammation was monitored with [18F]CB251-PET/MR and BLI. To evaluate the effects of anti-inflammatory agents on intracranial inflammation, an inflammatory cytokine inhibitor, 2-cyano-3, 12-dioxooleana-1, 9-dien-28-oic acid methyl ester (CDDO-Me) was administered in intracranial LPS challenged mice. Results: The ratio of IC50 values of [18F]CB251 in HAB to LAB indicated similar binding affinity to WT and mutant TSPO and was less affected by TSPO polymorphisms. [18F]CB251 was specific for TSPO, and its cellular uptake reflected the amount of TSPO. Higher [18F]CB251 uptake was also observed in activated immune cells. Simultaneous [18F]CB251-PET/MRI showed that [18F]CB251 radioactivity was co-registered with the MR signals in the same region of the brain of LPS-injected mice. Luciferase-expressing peripheral immune cells were located at the site of LPS-injected right striatum. Quantitative evaluation of the anti-inflammatory effect of CDDO-Me on neuroinflammation was successfully monitored with TSPO-targeting [18F]CB251-PET/MR and BLI. Conclusion: Our results indicate that [18F]CB251-PET has great potential for detecting neuroinflammation with higher TSPO selectivity regardless of polymorphisms. Our multimodal imaging system, [18F]CB251-PET/MRI, tested for evaluating the efficacy of anti-inflammatory agents in preclinical studies, might be an effective method to assess the severity and therapeutic response of neuroinflammation.

Malignant Peritoneal Mesothelioma Masquerades as Peritoneal Metastasis on (18)F-FDG PET/CT Scans; a Rare Diagnosis that Should Not Be Missed.

Malignant peritoneal mesothelioma (MPM) is a rare but fatal tumor. The clinical presentations and imaging findings are nonspecific and resemble various diseases, including peritoneal metastasis. Imaging findings of MPH on (18)F-(18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) are diverse and not well described. We report the two cases of biopsy-proven MPH using (18)F-FDG PET/CT. In our cases, interesting disease patterns-including MPH arising from visceral peritoneal lining of kidney that suffer from polycystic disease and from the parietal peritoneum beneath the appendectomy scar-were presented. One case showed classical metastases localized within the abdominal cavity; while the other case exhibited the rare pattern of extensive multi-organ metastases. By knowing the possible variations and diagnostic pitfalls of (18)F-FDG PET/CT findings in MPM, more accurate interpretation of such mysterious cancer is attainable.

Autoclustering of Non-small Cell Lung Carcinoma Subtypes on (18)F-FDG PET Using Texture Analysis: A Preliminary Result.

PURPOSE: Texture analysis on (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) scan is a relatively new imaging analysis tool to evaluate metabolic heterogeneity. We analyzed the difference in textural characteristics between non-small cell lung carcinoma (NSCLC) subtypes, namely adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). METHODS: Diagnostic (18)F-FDG PET/computed tomography (CT) scans of 30y patients (median age, 67; range, 42-88) with NSCLC (17 ADC and 13 SqCC) were retrospectively analyzed. Regions of interest were manually determined on selected transverse image containing the highest SUV value in tumors. Texture parameters were extracted by histogram-based algorithms, absolute gradient-based algorithms, run-length matrix-based algorithms, co-occurrence matrix-based algorithms, and autoregressive model-based algorithms. Twenty-four out of hundreds of texture features were selected by three algorithms: Fisher coefficient, minimization of both classification error probability and average correlation, and mutual information. Automated clustering of tumors was based on the most discriminating feature calculated by linear discriminant analysis (LDA). Each tumor subtype was determined by histopathologic examination after biopsy and surgery. RESULTS: Fifteen texture features had significant different values between ADC and SqCC. LDA with 24 automate-selected texture features accurately clustered between ADC and SqCC with 0.90 linear separability. There was no high correlation between SUVmax and texture parameters (|r| ≤ 0.62). CONCLUSION: Each subtype of NSCLC tumor has different metabolic heterogeneity. The results of this study support the potential of textural parameters on FDG PET as an imaging biomarker.

Total lesion glycolysis as the best 18F-FDG PET/CT parameter in differentiating intermediate-high risk adrenal incidentaloma.

OBJECTIVE: Characterization of intermediate-high risk adrenal incidentaloma (AI) is important because biopsy or surgery should be performed to confirm the malignancy. We investigated which parameters of F-fluorodeoxyglucose ((18)F-FDG) PET/computed tomography (CT) had an additive role in distinguishing malignancies in patients with incidental adrenal masses of intermediate-high risk. METHODS: From January 2008 to July 2013, 52 patients with a pathologically proven diagnosis of AI were retrospectively enrolled (age=56.4±12.7 years, M : F=34 : 18; benign : malignant=14 : 38). Volumetric parameters were size and volume according to combined CT, and metabolic parameters were peak standardized uptake value (SUV(peak)), maximum SUV (SUV(max)), mean SUV (SUV(mean)), and tumor-to-background ratio (SUV(max) of adrenal mass/SUV(mean) of liver). Metabolovolumetric parameters of metabolic tumor volume and total lesion glycolysis (TLG, SUV(mean)×metabolic tumor volume) were also included and compared with the diagnostic value. In addition, the highest diagnostic parameters among volumetric and metabolic parameters were combined and compared in terms of diagnostic accuracy. RESULTS: Compared with benign adrenal adenoma, malignant lesions showed significantly higher values of all (18)F-FDG PET/CT volumetric, metabolic, and metabolovolumetric parameters. Size showed the highest area under the curve (AUC) of 0.759 among the volumetric parameters, and SUV(peak) showed the highest AUC of 0.853 among the metabolic parameters. Among all the PET/CT parameters, TLG showed the highest AUC of 0.900, with a sensitivity of 92.1% and specificity of 78.6% at a cutoff of 12.0. The combined value of size and SUV(peak) showed lower diagnostic value than TLG. CONCLUSION: We found that TLG showed the best result in distinguishing intermediate-high risk AI among PET/CT parameters. TLG can be a useful PET/CT parameter for differential diagnosis of AI.

Correlation of 11C-methionine PET and diffusion-weighted MRI: is there a complementary diagnostic role for gliomas?

INTRODUCTION: 11C-Methionine (MET) PET and diffusion-weighted (DW) MRI are commonly used for evaluation of gliomas. We assessed the correlation between MET uptake and diffusion restriction measured on DW MRI in glioma. MATERIALS AND METHODS: Thirty-one patients with gliomas, who were initially examined with MET PET and DW MRI, were enrolled retrospectively. MET PET and apparent diffusion coefficient (ADC) images were coregistered to each other, using rigid-body transformation. Tumor-to-normal count density ratio of the cortex (TNR) and normalized apparent diffusion coefficient (nADC) value were measured for each voxel on the MET PET and ADC map. The maximum TNR (TNRmax) and minimum nADC (nADCmin) were obtained for each tumor. Correlations between those parameters were evaluated. RESULTS: The TNRmax and nADCmin values of a glioma were significantly correlated (r=-0.42). TNRmax and nADCmin were significantly correlated with glioma grades. Furthermore, TNRmax and nADCmin showed a trend for correlation with the Ki-67 index. We analyzed the correlation between voxel-based TNR and ADC within a tumor and observed no correlation between them. Regions with high MET uptake did not correspond with regions with low nADC. CONCLUSION: We found a negative correlation between TNRmax and nADCmin for each glioma; however, MET uptake and ADC within a tumor were independent of each other and were heterogeneous. The two parameters represent different biological features; thus, as a comprehensive approach, MET PET and DW MRI might have a complementary role in the characterization of gliomas.

Accuracy of 18F fluorodeoxyglucose positron emission tomography/computed tomography in staging of pediatric sarcomas.

The present study was conducted to clarify the diagnostic accuracy of 18F-fluoro-2-deoxy-D-glucose (18FDG) positron emission tomography (PET)/computed tomography (CT) in the staging in pediatric sarcomas. Fifty pediatric patients with histologically proven sarcomas who underwent 18FDG PET/CT before treatment were evaluated retrospectively for the detection of nodal and distant metastases. Diagnostic accuracy of 18FDG PET/CT in detecting nodal and distant metastases was compared with that of 18FDG PET and conventional imaging (CI). The images were reviewed and a diagnostic consensus was reached by 3 observers. REFERENCE standard was histologic examination in 15 patients and confirmation of an obvious progression in size of the lesions on follow-up examinations. Nodal metastasis was correctly assessed in 48 patients (96%) with PET/CT, in contrast to 43 patients (86%) with PET, and 46 patients (92%) with CI. Diagnostic accuracies of nodal metastasis in 3 modalities were similar. Using PET/CT, distant metastasis was correctly assigned in 43 patients (86%), whereas interpretation based on PET alone or CI revealed distant metastasis in 33 patients (66%) and 35 patients (70%), respectively. Diagnostic accuracy of distant metastasis with PET/CT was significantly higher than that of PET (P=0.002) or CI (P=0.008). False negative results regarding distant metastasis by PET/CT in 7 patients (14%) were caused by subcentimetric lesions (n=4), bone marrow lesion (n=2), and soft tissue lesions (n=1). PET/CT is more accurate and probably more cost-effective than PET alone or CI regarding distant metastasis in pediatric sarcomas.