Thorsten Derlin

Feasibility of 18F-Sodium Fluoride PET/CT for Imaging of Atherosclerotic Plaque

The aim of this study was to examine the prevalence, distribution, and topographic relationship of vascular 18F-sodium fluoride uptake and arterial calcification in major arteries. Methods: Image data obtained from 75 patients undergoing whole-body 18F-sodium fluoride PET/CT were evaluated retrospectively. Arterial radiotracer uptake and calcification were analyzed qualitatively and semiquantitatively. Results: 18F-sodium fluoride uptake was observed at 254 sites in 57 (76%) of the 75 study patients, and calcification was observed at 1,930 sites in 63 (84%) of the patients. Colocalization of radiotracer accumulation and calcification could be observed in 223 areas of uptake (88%). However, only 12% of all arterial calcification sites showed increased radiotracer uptake. Conclusion: Our data indicate the feasibility of 18F-sodium fluoride PET/CT for the imaging of mineral deposition in arterial wall alterations. 18F-sodium fluoride PET/CT may provide relevant information about the morphologic and functional properties of calcified plaque.

Correlation of Inflammation Assessed by 18F-FDG PET, Active Mineral Deposition Assessed by 18F-Fluoride PET, and Vascular Calcification in Atherosclerotic Plaque: A Dual-Tracer PET/CT Study

Formation and progression of atherosclerotic plaque is a dynamic and complex process involving various pathophysiologic steps including inflammation and calcification. The purpose of this study was to compare macrophage activity as determined by 18F-FDG PET and ongoing mineral deposition as measured by 18F-sodium fluoride PET in atherosclerotic plaque and to correlate these findings with calcified plaque burden as assessed by CT. Methods: Forty-five patients were examined by whole-body 18F-FDG PET, 18F-sodium fluoride PET, and CT. Tracer uptake in various arterial segments was analyzed both qualitatively and semiquantitatively by measuring the blood-pool–corrected standardized uptake value (target-to-background ratio [TBR]). The pattern of tracer uptake in atherosclerotic lesions was compared after color-coded multistudy image fusion of PET and CT studies. The Fisher exact test and the Spearman correlation coefficient rs were used for statistical analysis of image-based results and cardiovascular risk factors. Intra- and interrater reproducibility were evaluated using the Cohen κ. Results: 18F-sodium fluoride uptake was observed at 105 sites in 27 (60%) of the 45 study patients, and mean TBR was 2.3 ± 0.7. 18F-FDG uptake was seen at 124 sites in 34 (75.6%) patients, and mean TBR was 1.5 ± 0.3. Calcified atherosclerotic lesions were observed at 503 sites in 34 (75.6%) patients. Eighty-one (77.1%) of the 105 lesions with marked 18F-sodium fluoride uptake and only 18 (14.5%) of the 124 lesions with 18F-FDG accumulation were colocalized with arterial calcification. Coincident uptake of both 18F-sodium fluoride and 18F-FDG was observed in only 14 (6.5%) of the 215 arterial lesions with radiotracer accumulation. Conclusion: PET/CT with 18F-FDG and 18F-sodium fluoride may allow evaluation of distinct pathophysiologic processes in atherosclerotic lesions and might provide information on the complex interactions involved in formation and progression of atherosclerotic plaque.

18F-FDG PET/CT for detection and localization of residual or recurrent disease in patients with multiple myeloma after stem cell transplantation

PurposeThe aim of the study was to determine the diagnostic performance of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT for the detection and localization of residual or recurrent disease in patients with multiple myeloma (MM) after stem cell transplantation.MethodsA total of 197 whole-body 18F-FDG PET/CT scans were performed in 99 patients with MM at different time points in the course of disease after autologous or allogeneic stem cell transplantation. Post-transplant PET/CT scans and clinical remission status as determined by the clinical gold standard (Uniform Response Criteria) were analysed and compared.ResultsA total of 576 focal osseous and extramedullary lesions were detected in 79 scans. Additional diffuse bone marrow involvement was detected in 17 patients. 18F-FDG PET/CT had a sensitivity of 54.6%, a specificity of 82.1%, a positive predictive value of 82.3%, a negative predictive value of 54.2% and an overall accuracy of 65.5%. The sensitivity of 18F-FDG PET/CT was shown to depend on the disease category according to the Uniform Response Criteria for myeloma.ConclusionIn patients with MM in the post-transplant setting, 18F-FDG PET/CT may (1) contribute to the detection and localization of disease, (2) provide information about the extent of distinct myeloma manifestations and the total disease burden and (3) add information about the metabolic activity of disease, but (4) has substantially lower sensitivity for this purpose compared to the pretreatment setting.

Molecular Imaging of the Chemokine Receptor CXCR4 After Acute Myocardial Infarction.

OBJECTIVES An assay for molecular imaging of myocardial CXCR4 expression was evaluated, in order to obtain mechanistic insights noninvasively based on quantitative positron emission tomography (PET). BACKGROUND The chemokine receptor CXCR4 has emerged as a therapeutic target after acute myocardial infarction (AMI), because of its role in inflammatory and progenitor cell recruitment. METHODS PET with the specific CXCR4 ligand, gallium-68 ((68)Ga)-pentixafor, was performed in mice (n = 53) and compared with ex vivo autoradiography, immunohistochemistry, and left ventricular flow cytometry. In addition, 12 patients were imaged at 2 to 8 days after AMI. RESULTS In mice, (68)Ga-pentixafor identified regional CXCR4 upregulation in the infarct region, peaking at 3 days (infarct/remote [I/R] ratio 1.5 ± 0.2 at 3 days vs. 1.2 ± 0.3 at 7 days; p = 0.03), corresponding to a flow cytometry-based peak of CD45+ leukocytes and immunohistochemical detection of CD68+ macrophages and Ly6G+ granulocytes. Blockade with the CXCR4 antagonist AMD3100 abolished the signal. No specific uptake was found in sham-operated or control animals. Long-term treatment with oral enalapril attenuated the CXCR4 signal (I/R 1.2 ± 0.2 at 3 days and 1.0 ± 0.0.1 at 7 days; p = 0.01 vs. untreated). Patients showed variable degrees of CXCR4 upregulation in the infarct region. No single clinical parameter allowed for prediction of CXCR4 signal strength. At multivariate analysis, a combination of infarct size and time after reperfusion predicted the CXCR4 infarct signal (rmultiple = 0.73; p = 0.03). Infarct signal in the myocardium was paralleled by elevated pentixafor uptake in bone marrow (r = 0.61; p = 0.04), which highlighted systemic interactions. CONCLUSIONS Targeted PET imaging with (68)Ga-pentixafor identifies the global and regional CXCR4 expression pattern in myocardium and systemic organs. CXCR4 upregulation after AMI coincides with inflammatory cell infiltration, but shows interindividual variability in patients. This may have implications for the response to CXCR4- or other inflammation-targeted therapy, and for subsequent ventricular remodeling.

Comparative Effectiveness of 18f-fdg Pet/ct Versus Whole-body Mri for Detection of Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis Type 1

Purpose The aim of this study was to compare the diagnostic performance of 18F-fluorodeoxyglucose (FDG) PET/CT and whole-body MRI for the detection of malignant peripheral nerve sheath tumors (MPNSTs) in patients with neurofibromatosis type 1, and to evaluate a panel of imaging-based criteria serving that purpose. Patients and Methods Thirty-one patients were examined by whole-body MRI and 18F-FDG PET/CT. A panel of imaging-based criteria including tumor region, size, shape, margin definition, contrast enhancement, heterogeneity before and after contrast, intratumoral lobulation, target sign, and mean and maximum standardized uptake values (SUVs) were evaluated. A SUVmax cut-off value of 3.5 was used for lesion analysis. Histopathologic evaluation and/or clinical follow-up served as the reference standard. Results 18F-FDG PET/CT had a sensitivity of 100%, whereas MRI had a sensitivity of 66.7%. On PET/CT, tumor size (P < 0.005), SUVmax (P < 0.0001), SUVmean (P < 0.0001), and tracer uptake heterogeneity (P = 0.002) were significantly associated with MPNSTs. On MRI, intratumoral lobulation (P < 0.02), ill-defined margins (P = 0.007), and irregular enhancement on T1-weighted imaging (P < 0.001) were significantly associated with MPNSTs. Conclusions Both PET/CT and whole-body MRI may distinguish benign and malignant PNSTs, but PET/CT has higher sensitivity for that purpose. Imaging-based criteria for identification of MPNSTs on both modalities were identified. False-positive results, requiring biopsy or clinical follow-up, may be reduced by using a combination of MRI and PET derived markers, but only at the price of reduced sensitivity.

Diffusion weighted MRI and 18F-FDG PET/CT in non-small cell lung cancer (NSCLC): Does the apparent diffusion coefficient (ADC) correlate with tracer uptake (SUV)?

INTRODUCTION To investigate the potential correlation of the apparent diffusion coefficient assessed by diffusion-weighted MRI (DWI) and glucose metabolism determined by the standardized uptake value (SUV) at 18F-FDG PET/CT in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS 18F-FDG PET/CT and DWI (TR/TE, 2000/66 ms; b-values, 0 and 500 s/mm(2)) were performed in 41 consecutive patients with histologically verified NSCLC. Analysing the PET-CT data calculation of the mean (SUV(mean)) and maximum (SUV(max)) SUV was performed. By placing a region-of-interest (ROI) encovering the entire tumor mean (ADC(mean)) and minimum ADC (ADC(min)) were determined by two independent radiologists. Results of 18F-FDG PET-CT and DWI were compared on a per-patient basis. For statistical analysis Pearsons correlation coefficient, Bland-Altman and regression analysis were assessed. RESULTS Data analysis revealed a significant inverse correlation of the ADC(min) and SUV(max) (r=-0.46; p=0.032). Testing the correlation of the ADC(min) and SUV(max) for each histological subtype separately revealed that the inverse correlation was good for both adenocarcinomas (r=-0.47; p=0.03) and squamouscell carcinomas (r=-0.71; p=0.002), respectively. No significant correlation was found for the comparison of ADC(min) and SUV(mean) (r=-0.29; p=0.27), ADC(mean) vs. SUV(mean) (r=-0.28; p=0.31) or ADC(mean) vs. SUV(max) (r=-0.33; p=0.23). The κ-value of 0.88 indicated a good agreement between both observers. CONCLUSION This preliminary study is the first to verify the relation between the SUV and the ADC in NSCLC. The significant inverse correlation of these two quantitative imaging approaches points out the association of metabolic activity and tumor cellularity. Therefore, DWI with ADC measurement might represent a new prognostic marker in NSCLC.

Asphericity of pretherapeutic tumour FDG uptake provides independent prognostic value in head-and-neck cancer

AbstractObjectiveTo propose a novel measure, namely the ‘asphericity’ (ASP), of spatial irregularity of FDG uptake in the primary tumour as a prognostic marker in head-and-neck cancer.MethodsPET/CT was performed in 52 patients (first presentation, n = 36; recurrence, n = 16). The primary tumour was segmented based on thresholding at the volume-reproducible intensity threshold after subtraction of the local background. ASP was used to characterise the deviation of the tumour’s shape from sphere symmetry. Tumour stage, tumour localisation, lymph node metastases, distant metastases, SUVmax, SUVmean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were also considered. The association of overall (OAS) and progression-free survival (PFS) with these parameters was analysed.ResultsCox regression revealed high SUVmax [hazard ratio (HR) = 4.4/7.4], MTV (HR = 4.6/5.7), TLG (HR = 4.8/8.9) and ASP (HR = 7.8/7.4) as significant predictors with respect to PFS/OAS in case of first tumour manifestation. The combination of high MTV and ASP showed very high HRs of 22.7 for PFS and 13.2 for OAS. In case of recurrence, MTV (HR = 3.7) and the combination of MTV/ASP (HR = 4.2) were significant predictors of PFS.ConclusionsASP of pretherapeutic FDG uptake in the primary tumour improves the prediction of tumour progression in head-and-neck cancer at first tumour presentation.Key Points•Asphericity (ASP) characterises the spatial heterogeneity of FDG uptake in tumours • ASP is a promising prognostic parameter in head-and-neck cancer • ASP is useful for identification of high-risk patients with head-and-neck cancer

Contrast-Enhanced [18F]fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography for Staging and Radiotherapy Planning in Patients With Anal Cancer

PURPOSE The practice of surgical staging and treatment of anal cancer has been replaced by noninvasive staging and combined modality therapy. For appropriate patient management, accurate lymph node staging is crucial. The present study evaluated the feasibility and diagnostic accuracy of contrast-enhanced [(18)F]fluoro-2-deoxy-d-glucose ([(18)F]FDG)-positron emission tomography/computed tomography (PET/CT) for staging and radiotherapy planning of anal cancer. METHODS AND MATERIALS A total of 22 consecutive patients (median age, 61 years old) with anal cancer underwent complete staging evaluation including physical examination, biopsy of the primary tumor, and contrast-enhanced (ce)-PET/CT. Patients were positioned as they would be for their subsequent radiotherapy. PET and CT images were evaluated independently for detectability and localization of the primary tumor, pelvic and inguinal lymph nodes, and distant metastasis. The stage, determined by CT or PET alone, and the proposed therapy planning were compared with the stage and management determined by ce-PET/CT. Data from ce-PET/CT were used for radiotherapy planning. RESULTS ce-PET/CT revealed locoregional lymph node metastasis in 11 of 22 patients (50%). After simultaneous reading of PET and CT data sets by experienced observers, 3 patients (14%) were found to have sites of disease not seen on CT that were identified on PET. Two patients had sites of disease not seen on PET that were identified on CT. In summary, 2 patients were upstaged, and 4 patients were downstaged due to ce-PET/CT. However, radiotherapy fields were changed due to the results from ce-PET/CT in 23% of cases compared to CT or PET results alone. CONCLUSIONS ce-PET/CT is superior to PET or CT alone for staging of anal cancer, with significant impact on therapy planning.

Imaging of multiple myeloma: Current concepts

Medical imaging is of crucial importance for diagnosis and initial staging as well as for differentiation of multiple myeloma (MM) from other monoclonal plasma cell diseases. Conventional radiography represents the reference standard for diagnosis of MM due to its wide availability and low costs despite its known limitations such as low sensitivity, limited specificity and its inability to detect extraosseous lesions. Besides conventional radiography, newer cross-sectional imaging modalities such as whole-body low-dose computed tomography (CT), whole-body magnetic resonance imaging (MRI) and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT are available for the diagnosis of osseous and extraosseous manifestations of MM. Whole-body low-dose CT is used increasingly, replacing conventional radiography at selected centers, due to its higher sensitivity for the detection of osseous lesions and its ability to diagnose extraosseous lesions. The highest sensitivity for both detection of bone marrow disease and extraosseous lesions can be achieved with whole-body MRI and (18)F-FDG PET/CT. According to current evidence, MRI is the most sensitive method for initial staging while (18)F-FDG PET/CT allows monitoring of treatment of MM. There is an evolving role for assessment of treatment response using newer MR imaging techniques. Future studies are needed to further define the exact role of the different imaging modalities for individual risk stratification and therapy monitoring.

Follow-up of radiologically totally implanted central venous access ports of the upper arm: long-term complications in 127,750 catheter-days.

OBJECTIVE The purpose of this article is to retrospectively evaluate radiologically totally implanted central venous access ports (VAPs) of the upper arm in terms of safety, technical feasibility, and device-related complications. MATERIALS AND METHODS Five hundred seven consecutive patients (mean [± SD] age, 59.2 ± 11.4 years) who received a totally implanted central VAP between January 2005 and July 2010 were included. The insertion procedure was performed in an interventional radiology suite using the Seldinger technique. Neither antibiotic prophylaxis nor long-term anticoagulation was administered. RESULTS In 507 patients, a total of 523 devices were implanted. Of these 523 procedures, 512 complete datasets were available during follow-up. The primary technical success rate was 99.04%. All procedures were completed without major complications. During follow-up and with a total number of 127,750 days of totally implanted central VAP implantation (248 ± 279 days/patient; range, 1-1687 days/patient), 50 devices had to be revised because of complications (9.8%). Complications occurred at a mean of 114 ± 183 days (range, 1-1113 days) after placement. Early complications were noted in 21 of 512 cases (4.1%), and late complications were noted in 29 of 512 cases (5.7%). Complications were as follows: local infections, 4.9% (25/512); systemic infections, 0.4% (2/512); venous thrombosis, 1.6% (8/512); paralysis of the median nerve, 0.6% (3/512); skin dehiscence at the port site, 0.2% (1/512); and mechanical problems including catheter line displacement, port hub rotation, and catheter fracture, 2.1% (11/512). CONCLUSION Radiologic placement of a totally implanted central VAP is a safe procedure with a low rate of both early and late device-related complications. The method is effective for delivery of chemotherapy, parenteral nutrition, and frequent IV medication.