Clinical usefulness of F-18 FDG PET in lymphoepithelioma-like gastric carcinoma

PurposeLymphoepithelioma-like carcinoma (LELC) is a rare type of gastric cancer. We evaluated the clinical usefulness of F-18 FDG positron emission tomography/computed tomography (PET/CT) in LELC of stomach.Materials and methodsA total of 28 patients (mean age = 59 years) who underwent preoperative F-18 FDG PET/CT were enrolled retrospectively. Nine patients underwent follow-up F-18 FDG PET/CT. Pathologic information was obtained through gastrectomy and the association with Epstein-Barr virus (EBV) was investigated in 26 patients.ResultsPET/CT detected 85.0% (17/20) of advanced gastric cancers (AGC) and 12.5% (1/8) of early gastric cancers (EGC). Most tumors (23/26, 88.5%) were EBV-associated. The maximum standardized uptake value of FDG-avid tumors was 7.5 ± 3.0. The sensitivity and specificity of PET/CT for the presence of lymph node metastasis was 47.8% (11/23) and 100.0% (13/13), respectively. PET/CT also detected a hepatic sarcomatoid carcinoma in one patient. The specificity of PET/CT for distant metastasis or second malignancy was 96.3%. Follow-up PET/CT detected malignant lesions in 3 of 9 patients; a liver metastasis, recurrent hepatic sarcomatoid carcinomas and a metachronous cholangiocarcinoma. PET/CT correctly excluded recurrence in the rest of the patients (6/6). The sensitivity and specificity of PET/CT for detecting recurrence or second malignancy was 100% and 100%, respectively.ConclusionF-18 FDG PET/CT would be a useful tool in evaluating distant metastasis or recurrence in patients with gastric LELC.     

Role of 18F-FDG PET/CT in differentiation of a benign lesion and metastasis on the ribs of cancer patients

ObjectiveIncidental 18-Fluoro-2-deoxyglucose positron emission tomography (¹⁸F-FDG) uptake in the ribs is a relatively common finding on positron emission tomography/computed tomography (PET/CT) images of cancer patients. This study examined the role of ¹⁸F-FDG PET/CT in differentiating between benign lesions and metastases on the ribs.MethodsThis study included 264 lesions in 172 PET/CT cases with underlying malignancy showing newly developed indeterminate ¹⁸F-FDG rib uptake between June 2009 and May 2010. Patients with more than five FDG rib uptakes or hematologic malignancy were excluded. Malignancy was confirmed either histologically or by imaging studies, and clinical follow-up with serial images was at least 6 months. The maximum standardized uptake value (SUVmax) of the rib lesion was recorded. The FDG uptake patterns (focal or segmental; discrete or non-discrete) and CT findings (evidence of fracture, soft tissue lesions, osteoblastic and/or osteolytic lesions) were recorded.ResultsThere were 206 benign lesions and 58 metastases. The SUVmax was significantly higher in the metastatic group (3.0±1.8) than in the benign group (2.5±1.1), (P= .014). For the differential diagnosis between benign and metastatic lesions, the best SUVmax cut-off was determined to be 2.4. Significant indicators for metastasis were a segmental FDG uptake pattern (OR=10.262, 95% CI 4.151–25.371), presence of an osteoblastic/-lytic lesion (OR=22.903, 95% CI 10.468 to 50.108) and the absence of fractures on CT (OR=291.629, 95% CI 39.09–2175.666).ConclusionSUVmax alone is not sufficient to differentiate benign and metastatic rib lesions in cancer patients. The diagnostic accuracy can be further increased when findings of the CT part of PET/CT are considered.     

F-18 FDG PET/CT metabolic tumor volume predicts overall survival in patients with disseminated epithelial ovarian cancer

ObjectiveWe evaluated the prognostic impact of quantitative assessment by maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and tumour lesion glycolysis (TLG) on [F-18] FDG PET/CT for patients with peritoneal carcinomatosis from epithelial ovarian cancer (EOC).MethodsThirty-one patients with EOC underwent PET/CT for an early restaging after cytoreductive surgery, having been diagnosed with carcinomatosis (before chemotherapy). The SUVmax, MTV (cm³; 42% threshold) and TLG (g) were registered on residual peritoneal lesions. The patients were followed up 20 ± 12 months thereafter. The PET/CT results were compared to overall survival (OS).ResultsThe Kaplan-Meier survival analysis for the SUVmax did not reveal significant differences in OS (p = 0.48). The MTV survival analysis showed a significant higher OS in patients presenting with a higher tumour burden than those with less tumour burden (p = 0.01; 26 vs. 14 months), whereas TLG exhibited a similar trend though not significant (p = 0.06). Apart from chemo-resistance, the higher the MTV, the better will be the response to chemotherapy.ConclusionsQuantitative assessment by MTV rather than by SUVmax and TLG on PET/CT may be helpful for stratifying patients who present with peritoneal carcinomatosis from EOC, in order to implement the appropriate therapeutic regimen.     

Adrenergic pathway activation enhances brown adipose tissue metabolism: A [18 F]FDG PET/CT study in mice

ObjectivePharmacologic approaches to study brown adipocyte activation in vivo with a potential of being translational to humans are desired. The aim of this study was to examine pre- and postsynaptic targeting of adrenergic system for enhancing brown adipose tissue (BAT) metabolism quantifiable by [¹⁸ F]fluoro-2-deoxyglucose ([¹⁸ F]FDG) positron emission tomography (PET)/computed tomography (CT) in mice.MethodsA β₃-adrenoreceptor selective agonist (CL 316243), an adenylyl cyclase enzyme activator (forskolin) and a potent blocker of presynaptic norepinephrine transporter (atomoxetine), were injected through the tail vein of Swiss Webster mice 30 minutes before intravenous (iv) administration of [¹⁸ F]FDG. The mice were placed on the PET/CT bed for 30 min PET acquisition followed by 10 min CT acquisition for attenuation correction and anatomical delineation of PET images.ResultsActivated interscapular (IBAT), cervical, periaortic and intercostal BAT were observed in 3-dimentional analysis of [¹⁸ F]FDG PET images. CL 316243 increased the total [¹⁸ F]FDG standard uptake value (SUV) of IBAT 5-fold greater compared to that in placebo-treated mice. It also increased the [¹⁸ F]FDG SUV of white adipose tissue (2.4-fold), and muscle (2.7-fold), as compared to the control. There was no significant difference in heart, brain, spleen and liver uptakes between groups. Forskolin increased [¹⁸ F]FDG SUV of IBAT 1.9-fold greater than that in placebo-treated mice. It also increased the [¹⁸ F]FDG SUV of white adipose tissue (2.2-fold) and heart (5.4-fold) compared to control. There was no significant difference in muscle, brain, spleen, and liver uptakes between groups. Atomoxetine increased [¹⁸ F]FDG SUV of IBAT 1.7-fold greater than that in placebo-treated mice. There were no significant differences in all other organs compared to placebo-treated mice except liver (1.6 fold increase). A positive correlation between SUV levels of IBAT and CT Hounsfield unit (HU) (R² = 0.55, p < 0.001) and between CT HU levels of IBAT and liver (R² = 0.69, p < 0.006) was observed.ConclusionsThe three pharmacologic approaches reported here enhanced BAT metabolism by targeting different sites in adrenergic system as measured by [¹⁸ F]FDG PET/CT.     

Whole-body 18F-FDG PET/CT for M staging in the patient with newly diagnosed nasopharyngeal carcinoma: Who needs?

ObjectiveAlthough whole-body fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT) (¹⁸F-FDG PET/CT) is commonly used for M staging of newly diagnosed nasopharyngeal carcinoma (NPC), some patients may not benefit from this procedure. The present study investigated which patients require this modality for M staging.MethodsWhole-body ¹⁸F FDG PET/CT results and clinical data were collected for 264 patients with newly diagnosed NPC. The relationships between distant metastasis and age, gender, pathological type, lesion size, SUVmax-T, T staging, N staging, SUVmax-N and Epstein-Barr virus (EBV) quantity were retrospectively analysed to identify factors associated with increased risk.ResultsOf the 264 patients, only 37 (14.0%) were diagnosed with distant metastasis. Using multiple logistic regression analysis, EBV-positivity (OR = 13.1; 95% CI:1.61,106.80), N staging (OR = 3.05; 95% CI:1.41,6.63) and T staging (OR = 2.16; 95% CI:1.10, 4.24) were significantly related to distant metastasis (all P < 0.05). EBV DNA levels ≥ 9000 copies/ml, N3 stage and T4 stage were identified as high risk factors. A low risk of distant metastasis was found in patients with 0–1 risk factors and in those with 2 specific risk factors, T3/T4 and N2/N3 staging. Patients with EBV DNA levels ≥9000 copies/ml and N3 or T4 staging and those with 3 risk factors had a medium or high risk, with a much higher incidence of distant metastasis (χ² = 29.896, P = 0.000), and needed a whole-body ¹⁸F FDG PET/CT for M staging.ConclusionsDue to the low incidence of distant metastasis, only patients with medium or high risk need to undergo a whole-body scan.     

Biologic correlation between glucose transporters,hexokinase-II,Ki-67 and FDG uptake in malignant melanoma

IntroductionThe purpose of this study was to investigate the correlative association between tumoral 2-deoxy-2-[¹⁸ F]-fluoro-D-glucose (FDG) uptake, and the expressions of glucose transporter 1 (GLUT-1), glucose transporter 3 (GLUT-3), hexokinase II (HK-2), and Ki-67 expression in malignant melanoma.MethodsNineteen patients with histologically proven malignant melanoma and pretreatment FDG PET/CT performance were involved in this preliminary study. For semi-quantitative analysis of FDG PET/CT, maximal standardized uptake values (SUVmax) were estimated. Immunohistochemical staining of tumor sections was performed for GLUT-1, GLUT-3, and HK-2, and for the cell proliferation maker Ki-67. Especially, by combining proportions and intensity of immunochemical staining, we evaluated modified immunohistologic scores of GLUT-1 and GLUT-3.ResultsThe SUVmax of malignant melanoma lesions ranged from 2 to 18.7 (average; 9.1 ± 5.4). Comparison between nodal and extranodal lesions revealed no significant difference of SUVmax (p = 0.97). GLUT-1 staining showed the most positive expression level (89.5%, 17/19) among the diverse immunohistochemical markers. There were significant relationships between FDG uptake of malignant melanoma and GLUT-1 proportion (p < 0.0001), GLUT-1 intensity (p < 0.0001), GLUT-3 proportion (p = 0.031), GLUT-3 intensity (p = 0.009), GLUT-1 immunohistologic scores (p < 0.0001), and GLUT-3 immunohistologic scores (p = 0.028). HK-2 was not expressed in all melanoma samples. Although Ki-67 expression showed a high grade in all staining, there was no significant link between FDG uptake and Ki-67 grades (p = 0.38).ConclusionsThe data in this preliminary study indicate that FDG uptake in malignant melanoma is determined by GLUT-1 and GLUT-3, whereas HK-2 and Ki-67 play no role in FDG uptake of malignant melanoma.     

Quantification accuracy of neuro-oncology PET data as a function of emission scan duration in PET/MR compared to PET/CT

ObjectivesTo evaluate and compare the effect of reduced acquisition time, as a surrogate of injected activity, on the PET quantification accuracy in PET/CT and PET/MR imaging.MethodsTwenty min ¹⁸F-FDG phantom measurements and 10 min ¹⁸F-FET brain scans were acquired in a Biograph-True-Point-True-View PET/CT (n = 8) and a Biograph mMR PET/MR (n = 16). Listmode data were repeatedly split into frames of 1 min to 10 min length and reconstructed using two different reconstruction settings of a 3D-OSEM algorithm: with post-filtering (“OSEM”), and without post-filtering but with resolution recovery (“PSF”). Recovery coefficients (RC_max, RC_A50) and standard uptake values (SUV_max, SUV_A50) were evaluated.ResultsRC_max (phantom) and SUV_max (patients) increased significantly when reducing the frame duration. Significantly lower deviations were observed for RC_A50 and SUV_A50, respectively, making them more appropriate to compare PET studies at different number of counts. No statistical significant differences were observed when using post-filtering and reducing the frame time to 4 min (RC_A50, reference 20 min, phantom) and to 3 min (SUV_A50, reference 10 min, patients).ConclusionsFor hybrid aminoacid brain imaging, frame duration (or injected activity) can potentially be reduced to 30% of the standard used in clinical routine without significant changes on the quantification accuracy of the PET images if adequate reconstruction settings and quantitative measures are used. Frame times below 4 min in the NEMA phantom are not advisable to obtain quantitative and reproducible measures.     

Differentiation and diagnosis of benign and malignant testicular lesions using 18F-FDG PET/CT

ObjectivesThe purpose of this study was to evaluate the differential diagnostic value of ¹⁸F-fluorodeoxy glucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) for benign and malignant testicular lesions.MethodsThe PET/CT scans of 53 patients with testicular lesions confirmed by biopsy or surgical pathology were retrospectively analyzed. There were 32 cases of malignant tumors and 21 cases of benign lesions. Differences in the maximum standardized uptake value (SUVmax) measurements and the SUVmax lesion/background ratios between benign and malignant lesions were analyzed. The diagnostic value of this PET/CT modality for the differential diagnosis of benign versus malignant testicular lesions was calculated.ResultsThe differences in the SUVmax measurements and the SUVmax lesion/background ratios between benign and malignant lesions were statistically significant (SUVmax: Z = −4.295, p = 0.000; SUVmax lesion/background ratio: Z = −5.219, p = 0.000); specifically, both of these indicators were higher in malignant lesions compared to benign lesions. An SUVmax of 3.75 was the optimal cutoff value to differentiate between benign and malignant testicular lesions. The diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of this PET/CT modality in the differential diagnosis of benign versus malignant testicular lesions were 90.6%, 80.9%, 86.8%, 87.9%, and 85.0%, respectively.Conclusions¹⁸F-FDG PET/CT can accurately identify benign and malignant testicular lesions.     

Prognostic value of pretreatment volume-based quantitative 18F-FDG PET/CT parameters in patients with malignant pleural mesothelioma

PurposeTo investigate the relationships between pretreatment volume-based quantitative ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) parameters and overall survival (OS) in patients with malignant pleural mesothelioma (MPM).Materials and methodsWe retrospectively reviewed data from 201 MPM patients, of whom 38 underwent surgical resection, and calculated the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), including primary tumors and nodal or distant metastatic lesions, on pretreatment ¹⁸F-FDG PET/CT. Relationships between clinicopathological factors (age, sex, performance status, European Organization for Research and Treatment of Cancer [EORTC] score, histological subtype, TNM stage, and treatment strategy), volume-based quantitative PET/CT parameters, and OS were evaluated using a Cox proportional hazards model and log-rank test.ResultsThe median follow-up was 15 months (range, 1–96 months; median, 17 months). In a univariate analysis of all patients, older age (p < 0.05), high EORTC score (p < 0.001), non-epithelioid histological subtype (p < 0.001), high T stage (p < 0.001), positive N/M status (p < 0.05, p < 0.001), advanced TNM stage (p < 0.001), non-surgical treatment (p < 0.001), and high SUVmax (p < 0.001), MTV (p < 0.001), or TLG (p < 0.001) were associated with significantly shorter OS. A multivariate analysis confirmed non-epithelioid subtype (hazard ratio [HR]: 1.69, 95% confidence interval [CI]: 1.14–2.48; p < 0.05), non-surgical treatment (HR: 0.58, 95% CI: 0.34–0.95; p < 0.05), and high TLG (HR: 1.97, 95% CI: 1.14–3.44; p < 0.05) as independent negative predictors.ConclusionsPretreatment volume-based quantitative ¹⁸F-FDG PET/CT parameters, especially TLG, could serve as potential surrogate markers for MPM prognosis.     

Impact of blood glucose,diabetes, insulin,and obesity on standardized uptake values in tumors and healthy organs on 18F-FDG PET/CT

IntroductionChronically altered glucose metabolism interferes with ¹⁸F-FDG uptake in malignant tissue and healthy organs and may therefore lower tumor detection in ¹⁸F-FDG PET/CT. The present study assesses the impact of elevated blood glucose levels (BGL), diabetes, insulin treatment, and obesity on ¹⁸F-FDG uptake in tumors and biodistribution in normal organ tissues.Methods¹⁸F-FDG PET/CT was analyzed in 90 patients with BGL ranging from 50 to 372 mg/dl. Of those, 29 patients were diabetic and 21 patients had received insulin prior to PET/CT; 28 patients were obese with a body mass index > 25. The maximum standardized uptake value (SUV_max) of normal organs and the main tumor site was measured. Differences in SUV_max in patients with and without elevated BGLs, diabetes, insulin treatment, and obesity were compared and analyzed for statistical significance.ResultsIncreased BGLs were associated with decreased cerebral FDG uptake and increased uptake in skeletal muscle. Diabetes and insulin diminished this effect, whereas obesity slightly enhanced the outcome. Diabetes and insulin also increased the average SUV_max in muscle cells and fat, whereas the mean cerebral SUV_max was reduced. Obesity decreased tracer uptake in several healthy organs by up to 30%. Tumoral uptake was not significantly influenced by BGL, diabetes, insulin, or obesity.ConclusionsChanges in BGLs, diabetes, insulin, and obesity affect the FDG biodistribution in muscular tissue and the brain. Although tumoral uptake is not significantly impaired, these findings may influence the tumor detection rate and are therefore essential for diagnosis and follow-up of malignant diseases.     

Emphysema quantification and lung volumetry in chest X-ray equivalent ultralow dose CT – Intra-individual comparison with standard dose CT

ObjectivesTo determine whether ultralow dose chest CT with tin filtration can be used for emphysema quantification and lung volumetry and to assess differences in emphysema measurements and lung volume between standard dose and ultralow dose CT scans using advanced modeled iterative reconstruction (ADMIRE).Methods84 consecutive patients from a prospective, IRB-approved single-center study were included and underwent clinically indicated standard dose chest CT (1.7 ± 0.6 mSv) and additional single-energy ultralow dose CT (0.14 ± 0.01 mSv) at 100 kV and fixed tube current at 70 mAs with tin filtration in the same session. Forty of the 84 patients (48%) had no emphysema, 44 (52%) had emphysema. One radiologist performed fully automated software-based pulmonary emphysema quantification and lung volumetry of standard and ultralow dose CT with different levels of ADMIRE. Friedman test and Wilcoxon rank sum test were used for multiple comparison of emphysema and lung volume. Lung volumes were compared using the concordance correlation coefficient.ResultsThe median low-attenuation areas (LAA) using filtered back projection (FBP) in standard dose was 4.4% and decreased to 2.6%, 2.1% and 1.8% using ADMIRE 3, 4, and 5, respectively. The median values of LAA in ultralow dose CT were 5.7%, 4.1% and 2.4% for ADMIRE 3, 4, and 5, respectively. There was no statistically significant difference between LAA in standard dose CT using FBP and ultralow dose using ADMIRE 4 (p = 0.358) as well as in standard dose CT using ADMIRE 3 and ultralow dose using ADMIRE 5 (p = 0.966). In comparison with standard dose FBP the concordance correlation coefficients of lung volumetry were 1.000, 0.999, and 0.999 for ADMIRE 3, 4, and 5 in standard dose, and 0.972 for ADMIRE 3, 4 and 5 in ultralow dose CT.ConclusionsUltralow dose CT at chest X-ray equivalent dose levels allows for lung volumetry as well as detection and quantification of emphysema. However, longitudinal emphysema analyses should be performed with the same scan protocol and reconstruction algorithms for reproducibility.     

Higher breast cancer conspicuity on dbPET compared to WB-PET/CT

ObjectivesThe purpose of this study was to evaluate lesion detectability of a dedicated breast positron-emission tomography (dbPET) scanner for breast cancers with an updated reconstruction mode, comparing it to whole-body positron-emission tomography/computed tomography (WB-PET/CT).Materials and methodsA total of 179 histologically-proven breast cancer lesions in 150 females who underwent both WB-PET/CT and dbPET with ¹⁸F-fluorodeoxyglucose were retrospectively analyzed. The patient/breast/lesion-based sensitivities based on visual analysis were compared between dbPET and WB-PET/CT. For lesions visible on both PET images, SUVmax values of the tumors were measured, and tumor-to-background ratios (T/B ratios) of SUVmax were compared between the two scans. Subgroup analyses according to clinical tumor stage, histopathology and histological grade were also performed.ResultsPatient/breast/lesion-based sensitivities were 95%, 95%, and 92%, respectively, for dbPET, and 95%, 94%, and 88%, respectively, for WB-PET/CT. Mean ± standard deviation SUVmax values of FDG-avid tumors were 13.0 ± 9.7 on dbPET and 6.4 ± 4.8 on WB-PET. T/B ratios were also significantly higher in dbPET than in WB-PET/CT (8.1 ± 7.1 vs. 5.1 ± 4.5). In the subgroup analysis, no significant differences in sensitivities between dbPET and WB-PET/CT were found. However, T/B ratios of dbPET were significantly higher than those of WB-PET/CT in cT1c, cT2, cT3, invasive cancer, invasive carcinoma of no special type, mucinous carcinoma and Grades 1–3.ConclusionNo significant differences in sensitivities were identified between dbPET using an updated reconstruction mode and WB-PET/CT; however, T/B ratios of dbPET were significantly higher than those of WB-PET/CT, indicating higher tumor conspicuity on dbPET.     

Improved detection of melanoma metastases by iodine maps from dual energy CT

ObjectiveMetastatic disease in melanoma has an unpredictable nature with deposits in rare locations such as musculature. Dual energy CT (DECT) provides high contrast-visualization of enhancement by using spectral properties of iodine. Purpose of this study was to evaluate whether iodine maps from DECT improve lesion detection in staging examinations of melanoma patients.MethodsThis retrospective study was approved by IRB and written informed consent was obtained from all patients. 75 contrast-enhanced DECT scans (thorax and abdomen) from 75 melanoma patients (n = 69 stage IV; n = 6 stage III) were analysed. For each patient, conventional CT and iodine maps were reviewed independently by two radiologists. The number of lesions detected by reviewing the iodine maps following conventional CT was recorded. Unweighted Cohens Kappa coefficient (κ) was used for concordance analysis, Wilcoxon test for comparing lesion detection rates.ResultsIn 26 patients, at least one reader found additional lesions on iodine maps (inter-reader agreement 89%, κ = 0.74 (0.742–0.747)). Compared to grey-scale images, mean detection rate for metastases improved from 86% (range 82–90) to 94% (90–99%) (p ≤ 0.01), for muscle metastases from 8% (8-8%) to 99% (98–100%) (p ≤ 0.06). Findings included 2 pulmonary emboli.ConclusionIodine maps from DECT improve detection of metastases, especially muscle metastases, and relevant findings in staging examinations of melanoma patients.     

Antilipolytic drug boosts glucose metabolism in prostate cancer

IntroductionThe antilipolytic drug Acipimox reduces free fatty acid (FFA) levels in the blood stream. We examined the effect of reduced FFAs on glucose metabolism in androgen-dependent (CWR22Rv1) and androgen-independent (PC3) prostate cancer (PCa) xenografts.MethodsSubcutaneous tumors were produced in nude mice by injection of PC3 and CWR22Rv1 PCa cells. The mice were divided into two groups (Acipimox vs. controls). Acipimox (50 mg/kg) was administered by oral gavage 1 h before injection of tracers. 1 h after i.v. co-injection of 8.2 MBq (222 ± 6.0 μCi) ¹⁸ F-FDG and ~ 0.0037 MBq (0.1 μCi) ¹⁴C-acetate, ¹⁸ F-FDG imaging was performed using a small-animal PET scanner. Counting rates in reconstructed images were converted to activity concentrations. Quantification was obtained by region-of-interest analysis using dedicated software. The mice were euthanized, and blood samples and organs were harvested. ¹⁸ F radioactivity was measured in a calibrated γ-counter using a dynamic counting window and decay correction. ¹⁴C radioactivity was determined by liquid scintillation counting using external standard quench corrections. Counts were converted into activity, and percentage of the injected dose per gram (%ID/g) tissue was calculated.ResultsFDG biodistribution data in mice with PC3 xenografts demonstrated doubled average %ID/g tumor tissue after administration of Acipimox compared to controls (7.21 ± 1.93 vs. 3.59 ± 1.35, P = 0.02). Tumor-to-organ ratios were generally higher in mice treated with Acipimox. This was supported by PET imaging data, both semi-quantitatively (mean tumor FDG uptake) and visually (tumor-to-background ratios). In mice with CWR22Rv1 xenografts there was no effect of Acipimox on FDG uptake, either in biodistribution or PET imaging. ¹⁴C-acetate uptake was unaffected in PC3 and CWR22Rv1 xenografts.ConclusionsIn mice with PC3 PCa xenografts, acute administration of Acipimox increases tumor uptake of ¹⁸ F-FDG with general improvements in tumor-to-background ratios. Data indicate that administration of Acipimox prior to ¹⁸ F-FDG PET scans has potential to improve sensitivity and specificity in patients with castration-resistant advanced PCa.     

Dynamic contrast-enhanced perfusion area-detector CT assessed with various mathematical models: Its capability for therapeutic outcome prediction for non-small cell lung cancer patients with chemoradiotherapy as compared with that of FDG-PET/CT

PurposeTo directly compare the capability of dynamic first-pass contrast-enhanced (CE-) perfusion area-detector CT (ADCT) and PET/CT for early prediction of treatment response, disease progression and overall survival of non-small cell carcinoma (NSCLC) patients treated with chemoradiotherapy.Materials and methodsFifty-three consecutive Stage IIIB NSCLC patients who had undergone PET/CT, dynamic first-pass CE-perfusion ADCT, chemoradiotherapy, and follow-up examination were enrolled in this study. They were divided into two groups: 1) complete or partial response (CR + PR) and 2) stable or progressive disease (SD + PD). Pulmonary arterial and systemic arterial perfusions and total perfusion were assessed at targeted lesions with the dual-input maximum slope method, permeability surface and distribution volume with the Patlak plot method, tumor perfusion with the single-input maximum slope method, and SUV_max, and results were averaged to determine final values for each patient. Next, step-wise regression analysis was used to determine which indices were the most useful for predicting therapeutic effect. Finally, overall survival of responders and non-responders assessed by using the indices that had a significant effect on prediction of therapeutic outcome was statistically compared.ResultsThe step-wise regression test showed that therapeutic effect (r² = 0.63, p = 0.01) was significantly affected by the following three factors in order of magnitude of impact: systemic arterial perfusion, total perfusion, and SUV_max. Mean overall survival showed a significant difference for total perfusion (p = 0.003) and systemic arterial perfusion (p = 0.04).ConclusionDynamic first-pass CE-perfusion ADCT as well as PET/CT are useful for treatment response prediction in NSCLC patients treated with chemoradiotherapy.     

Estimating the amount of FDG uptake in physiological tissues

IntroductionIt is known that for a fixed amount of injected tracer, the amount available for a tissue of interest will be less if other tissues show intense uptake. The aim of this study was to estimate the magnitude of 2-deoxy-2-[¹⁸F]fluoro-d-glucose (18FDG) uptake amount in physiological tissues that may show an intense uptake in current clinical practice.MethodsA formula was established providing an estimate of the percentage of injected 18FDG molecules (P; in %) that are irreversibly trapped in an 18FDG-positive tissue during a PET examination.ResultsP ≅ 0.17*exp(−λt_acq)*TLG/W, where λ is the ¹⁸F physical decay constant, t_acq is the injection-acquisition time delay, TLG is total lesion glycolysis (g) and W is the patient weight (kg). The magnitude of P was calculated in two patients showing an intense uptake in brown fat, myocardium and bowels: 0.5, 3.5, and 4.2% respectively.ConclusionsA formula is available to quickly estimate the amount of 18FDG uptake in tissues. We suggest that the accumulation of different physiological uptakes may actually affect SUV quantification in a tissue of interest.     

Influence of free fatty acids on glucose uptake in prostate cancer cells

IntroductionThe study focuses on the interaction between glucose and free fatty acids (FFA) in malignant human prostate cancer cell lines by an in vitro observation of uptake of fluoro-2-deoxy-d-glucose (FDG) and acetate.MethodsHuman prostate cancer cell lines (PC3, CWR22Rv1, LNCaP, and DU145) were incubated for 2 h and 24 h in glucose-containing (5.5 mM) Dulbecco’s Modified Eagle’s Medium (DMEM) with varying concentrations of the free fatty acid palmitate (0–1.0 mM). Then the cells were incubated with [¹⁸ F]-FDG (1 μCi/mL; 0.037 MBq/mL) in DMEM either in presence or absence of glucose and in presence of varying concentrations of palmitate for 1 h. Standardized procedures regarding cell counting and measuring for ¹⁸ F radioactivity were applied. Cell uptake studies with ¹⁴C-1-acetate under the same conditions were performed on PC3 cells.ResultsIn glucose containing media there was significantly increased FDG uptake after 24 h incubation in all cell lines, except DU145, when upper physiological levels of palmitate were added. A 4-fold increase of FDG uptake in PC3 cells (15.11% vs. 3.94%/10⁶ cells) was observed in media with 1.0 mM palmitate compared to media with no palmitate. The same tendency was observed in PC3 and CWR22Rv1 cells after 2 h incubation. In glucose-free media no significant differences in FDG uptake after 24 h incubation were observed. The significant differences after 2 h incubation all pointed in the direction of increased FDG uptake when palmitate was added. Acetate uptake in PC3 cells was significantly lower when palmitate was added in glucose-free DMEM. No clear tendency when comparing FDG or acetate uptake in the same media at different time points of incubation was observed.ConclusionsOur results indicate a FFA dependent metabolic boost/switch of glucose uptake in PCa, with patterns reflecting the true heterogeneity of the disease.     

Differentiation of small intrahepatic mass-forming cholangiocarcinoma from small liver abscess by dual source dual-energy CT quantitative parameters

PurposeTo investigate the use of dual source dual-energy CT (DECT) quantitative parameters compared with the use of conventional CT for differentiating small (≤3 cm) intrahepatic mass-forming cholangiocarcinoma (IMCC) from small liver abscess (LA) during the portal venous phase (PVP).Material and methodsIn this institutional review board-approved, retrospective study, 64 patients with IMCCs and 52 patients with LAs who were imaged in PVP using dual-energy mode were included retrospectively. A radiologist drew circular regions of interest in the lesion on the virtual monochromatic images (VMI), color-coded iodine overlay images, and linear blending images with a linear blending ratio of 0.3 to obtain CT value, its standard deviation, slope (k) of spectral curve and normalized iodine concentration (NIC). Two radiologists assessed lesion type on the basis of qualitative CT imaging features.ResultsCT values on VMI at 50–130 keV (20 keV-interval), k, and NIC values were significantly higher in IMCCs than in LAs (p < 0.0001). The best single parameter for differentiating IMCC from LA was CT value at 90 keV, with sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 89.1%, 86.5%, 87.9%, 89.1%, and 86.5%, respectively. The best combination of parameters was CT value at 90 keV, k, and NIC, with values of 87.5%, 84.6%, 83.6%, 87.5%, and 84.6%, respectively. Compared with CT value at linear blending images, CT value at 90 keV showed greater sensitivity (89.1% vs 60.9%, p < 0.0001) and similar specificity (86.5% vs 84.6%, p = 1.0000), and combined CT value at 90 keV, k, and NIC showed greater sensitivity (87.5% vs 60.9%, p < 0.0001) and similar specificity (84.6% vs 84.6%, p = 1.0000). Compared with qualitative analysis, CT value at 90 keV showed greater sensitivity (89.1% vs 65.6%, p = 0.0059) and specificity (86.5% vs 69.2%, p = 0.0352), and combined CT value at 90 keV, k, and NIC showed greater sensitivity (87.5% vs 65.6%, p = 0.0094) and similar specificity (84.6% vs 69.2%, p > 0.05).ConclusionQuantitative analysis of dual source dual-energy CT quantitative parameters showed greater accuracy than quantitative and qualitative analyses of conventional CT for differentiating small IMCCs from small LAs on single PVP scan.     

Influence of fissure integrity on quantitative CT and emphysema distribution in emphysema-type COPD using a dedicated COPD software

ObjectivesFissure integrity (FI) plays a key role in selecting patients for interventional emphysema therapy. We investigated its interference with automated lobar segmentation in quantitative computed tomography (CT) and emphysema distribution.MethodsCT was available for 50 patients with chronic obstructive pulmonary disease (COPD). Lobe segmentation was performed fully automated by software and corrected manually. FI was evaluated visually using a %-scale. The influence of FI on emphysema ratio (ER = percentage of lung volume with density values < −950 HU), mean lung density (MLD), emphysema and total volume of adjacent lobes was analyzed. Lobe-based results were compared with respect to FI.ResultsDifferences in ER in adjacent lobes for complete vs. incomplete fissures were 12.4% for the right horizontal, 0.2% and 3% for the right oblique and 4.4% for the left oblique fissure (all p > 0.05). Results for emphysema comparing automated vs. manually corrected segmentation exceeded clinically acceptable values, but were not significantly affected by FI (p > 0.05). The widest limits of agreement for ER and MLD were noted in the right middle lobe ([−14, 17.4%], [−22.4, 32.4 Hounsfield Units]).ConclusionsAutomated lobe segmentation and emphysema distribution are not significantly affected by FI. Manual correction of automated lobar segmentation is still recommended in severe emphysema.     

Enhanced radiation damage caused by iodinated contrast agents during CT examination

ObjectiveTo access the effect of iodinate contrast agent (ICA) on DNA double-stand breaks (DSBs) in human peripheral blood lymphocytes during computed tomography (CT) examinations.Materials and methodsThis present study was approved by the institutional ethics committee; written informed patient consent was obtained from 70 patients. A total of 48 patients underwent computed tomography urography (CTU), in which only one time CT scanning was examined after injecting ICA, and 22 patients received unenhanced whole abdominal CT, among them 10 patients were selected to get ICA injection immediately after irradiation. Blood samples were taken from all patients prior to and immediately after CT scan, as well as 8 min after the injection of ICA. The lymphocytes in these blood samples were separated by using density-gradient centrifugation, fixed and immunostained with γH2AX antibody. The average number of phosphorylated histone H2AX (γH2AX) foci per lymphocyte was counted under a fluorescence microscopy. Differences in the number of γH2AX-foci were statistically analyzed using independent sample t test and one way ANOVA.ResultThe three patient groups had no significant differences in the baseline foci numbers(P > 0.05). The γH2AX-focus levels increased in both groups after CT scan. Patients who underwent CTU examinations had a greater DSBs level (mean ± standard error of mean, 0.945 ± 0.184 foci per cell) than those who received unenhanced whole abdominal CT scan (mean ± standard error of mean, 0.700 ± 0.112 foci per cell), increasing by about 37.9%; The ICA injected before CT scan itself had an effect on the DSBs, which increased DSBs level by approximately 90.3% (0.059 ± 0.018 v s 0.031 ± 0.025, P < 0.05), but no significant difference was found if added after irradiation, increasing DSBs level only by 3.2% approximately (0.711 ± 0.091 v s 0.689 ± 0.108, P = 0.499).ConclusionThe iodinated contrast agent itself can lead to an increase in the level of DSBs as assessed with γH2AX foci formation, and the application of ICA can amplify DNA damage induced by diagnostic x-ray procedures such as whole abdominal CT.