11C-Methionine-PET in Multiple Myeloma: A Combined Study from Two Different Institutions.
ABSTRACT: 11C-methionine (MET) has recently emerged as an accurate marker of tumor burden and disease activity in patients with multiple myeloma (MM). This dual-center study aimed at further corroboration of the superiority of MET as positron emission tomography (PET) tracer for staging and re-staging MM, as compared to 18F-2`-deoxy-2`-fluoro-D-glucose (FDG). 78 patients with a history of solitary plasmacytoma (n=4), smoldering MM (SMM, n=5), and symptomatic MM (n=69) underwent both MET- and FDG-PET/computed tomography (CT) at the University Centers of Würzburg, Germany and Navarra, Spain. Scans were compared on a patient and on a lesion basis. Inter-reader agreement was also evaluated. In 2 patients, tumor biopsies for verification of discordant imaging results were available. MET-PET detected focal lesions (FL) in 59/78 subjects (75.6%), whereas FDG-PET/CT showed lesions in only 47 patients (60.3%; p<0.01), accordingly disease activity would have been missed in 12 patients. Directed biopsies of discordant results confirmed MET-PET/CT results in both cases. MET depicted more FL in 44 patients (56.4%; p<0.01), whereas in two patients (2/78), FDG proved superior. In the remainder (41.0%, 32/78), both tracers yielded comparable results. Inter-reader agreement for MET was higher than for FDG (? = 0.82 vs ? = 0.72). This study demonstrates higher sensitivity of MET in comparison to standard FDG to detect intra- and extramedullary MM including histologic evidence of FDG-negative, viable disease exclusively detectable by MET-PET/CT. MET holds the potential to replace FDG as functional imaging standard for staging and re-staging of MM.
Project description:Multiple myeloma (MM) remains an essentially incurable hematologic malignancy originating from clonal plasma cells. This study evaluated the usefulness of the radiotracers (11)C-methionine (MET) and (18)F-2`-deoxy-2`-fluorodeoxyglucose (FDG) for staging and re-staging in MM. 43 patients with MM underwent both MET- and FDG-PET/CT for staging or re-staging within 3±2 days. Scans were compared on a patient and on a lesion basis. Tracer uptake was correlated with the degree of bone marrow (BM) involvement and standard clinical parameters of disease activity. Additionally, BM samples were stained for L-type amino acid transporter 1 (LAT1) expression in 15 patients. MET-PET detected focal lesions (FL) in 39/43 subjects (90.7%), whereas 10 patients were missed in FDG-PET/CT (detection rate, 33/43; 76.7%; p<0.05). MET depicted more FL in 28/43 patients (65.1%; p<0.001), whereas in the remainder (34.9%, n=15) both tracers yielded comparable results. LAT1 was highly expressed on the cell surface of myeloma cells. Both FDG and MET uptake correlated significantly with biopsy-proven BM involvement (p<0.001), with MET demonstrating a stronger correlation (SUVmean, r=0.9 vs r=0.6; SUVmax, r=0.88 vs r=0.58). Abnormal beta-2-microglobulin and free light chain levels correlated with the presence of focal intramedullary lesions detected in MET- or FDG-PET/CT (MET, p=0.006 and p=0.01, respectively; FDG, p=0.02 and p=0.01). MET appears to be superior to FDG for staging and re-staging of both intra- and extramedullary MM lesions. Tracer uptake correlates with BM involvement, ?2m and FLC levels and appears to be a more accurate marker of tumor burden and disease activity.
Project description:11C-methionine (11C-MET) is a new positron emission tomography (PET) tracer for the assessment of disease activity in multiple myeloma (MM) patients, with preliminary data suggesting higher sensitivity and specificity than 18F-fluorodeoxyglucose (18F-FDG). However, the value of tumor burden biomarkers has yet to be investigated. Our goals were to corroborate the superiority of 11C-MET for MM staging and to compare its suitability for the assessment of metabolic tumor burden biomarkers in comparison to 18F-FDG. Twenty-two patients with newly diagnosed, treatment-naïve symptomatic MM who had undergone 11C-MET and 18F-FDG PET/CT were evaluated. Standardized uptake values (SUV) were determined and compared with total metabolic tumor volume (TMTV) for both tracers: total lesion glycolysis (TLG) and total lesion 11C-MET uptake (TLMU). PET-derived values were compared to Revised International Staging System (R-ISS), cytogenetic, and serologic MM markers such as M component, beta 2 microglobulin (B2M), serum free light chains (FLC), albumin, and lactate dehydrogenase (LDH). In 11 patients (50%), 11C-MET detected more focal lesions (FL) than FDG (p < 0.01). SUVmax, SUVmean, SUVpeak, TMTV, and TLMU were also significantly higher in 11C-MET than in 18F-FDG (p < 0.05, respectively). 11C-MET PET biomarkers had a better correlation with tumor burden (bone marrow plasma cell infiltration, M component; p < 0.05 versus p = n.s. respectively). This pilot study suggests that 11C-MET PET/CT is a more sensitive marker for the assessment of myeloma tumor burden than 18F-FDG. Its implications for prognosis evaluation need further investigation.
Project description:Currently, there is a lack of data on the role of combined positron emission tomography-computed tomography (PET-CT) in the staging of early invasive primary breast cancer. We therefore evaluated the role of (18)F-fluorodeoxyglucose ((18)F-FDG)-PET-CT in this patient population.We prospectively recruited 70 consecutive patients (69 women, one man; mean age, 61.9 ± 8.1 years) with early primary breast cancer for staging with (18)F-FDG-PET-CT. All PET-CT images were interpreted by two readers (independently of each other). A third reader adjudicated any discrepancies. All readers had ?5 years of specific experience. Ethics board approval and informed consent were obtained.The mean clinical follow-up was 22.7 ± 12.6 months. The primary tumor was identified with PET-CT in 64 of 70 patients. Of the unidentified lesions, surgical pathology revealed two intraductal carcinomas, one invasive tubular carcinoma, and three invasive lobular carcinomas. Undiagnosed multifocal breast disease was shown in seven of 70 patients. PET-CT identified avid axillary lymph nodes in 19 of 70 patients, compared with 24 of 70 confirmed during surgery. There were four patients who were axillary node positive on PET but had no axillary disease at surgery. Five patients were reported with avid metastases. Two of those patients were treated for metastatic disease (nodal, lung, and liver in one and bone metastases in the other) following further imaging and clinical assessment. In the other three patients, lesions (lung, n = 1; pleural, n = 1; paratrachael node, n = 1) were subsequently diagnosed as benign lesions.Integrated (18)F-FDG-PET-CT may have a role in staging patients presenting with early breast cancer.
Project description:Background: Molecular imaging methods are currently used in the management of patients with lung cancer. Compared to non-small cell lung cancer, less data are available about the impact of molecular imaging using fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in staging patients with small cell lung cancer (SCLC). Performing a systematic review and meta-analysis, we aimed to provide quantitative data about the impact of 18F-FDG PET/CT in staging SCLC. Methods: A comprehensive literature search of studies on the use of 18F-FDG PET/CT in patients with SCLC was performed. Three different databases were screened (PubMed/MEDLINE, EMBASE, and Cochrane library databases) until June 2019. Only articles describing the impact of 18F-FDG PET/CT in staging patients with SCLC were selected. A pooled analysis evaluating the change of binary SCLC staging (limited-stage vs. extensive-stage disease) using 18F-FDG PET/CT was carried out. Results: Nine articles including 721 patients with SCLC were included in the systematic review. Compared to conventional staging, a superior diagnostic accuracy of 18F-FDG PET/CT was found. A change of binary SCLC staging using 18F-FDG PET/CT was demonstrated in 15% (95% confidence interval, 9-21%) of patients with SCLC. Currently, it is not clearly demonstrated that the use of 18F-FDG PET/CT for staging may improve the survival outcome of patients with SCLC. Conclusions: 18F-FDG PET/CT is a useful molecular imaging method for staging patients with SCLC because it can change the management in a significant number of patients. More large prospective studies and cost-effectiveness analyses on the impact of 18F-FDG PET/CT in staging patients with SCLC are needed.
Project description:PURPOSE:To provide clinically useful gadolinium-free whole-body cancer staging of children and young adults with integrated positron emission tomography/magnetic resonance (PET/MR) imaging in less than 1 h. PROCEDURES:In this prospective clinical trial, 20 children and young adults (11-30 years old, 6 male, 14 female) with solid tumors underwent 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET/MR on a 3T PET/MR scanner after intravenous injection of ferumoxytol (5 mg Fe/kg) and [18F]FDG (2-3 MBq/kg). Time needed for patient preparation, PET/MR image acquisition, and data processing was compared before (n = 5) and after (n = 15) time-saving interventions, using a Wilcoxon test. The ferumoxytol-enhanced PET/MR images were compared with clinical standard staging tests regarding radiation exposure and tumor staging results, using Fisher's exact tests. RESULTS:Tailored workflows significantly reduced scan times from 36 to 24 min for head to mid thigh scans (p < 0.001). These streamlined PET/MR scans were obtained with significantly reduced radiation exposure (mean 3.4 mSv) compared to PET/CT with diagnostic CT (mean 13.1 mSv; p = 0.003). Using the iron supplement ferumoxytol "off label" as an MR contrast agent avoided gadolinium chelate administration. The ferumoxytol-enhanced PET/MR scans provided equal or superior tumor staging results compared to clinical standard tests in 17 out of 20 patients. Compared to PET/CT, PET/MR had comparable detection rates for pulmonary nodules with diameters of equal or greater than 5 mm (94 vs. 100 %), yet detected significantly fewer nodules with diameters of less than 5 mm (20 vs 100 %) (p = 0.03). [18F]FDG-avid nodules were detected with slightly higher sensitivity on the PET of the PET/MR compared to the PET of the PET/CT (59 vs 49 %). CONCLUSION:Our streamlined ferumoxytol-enhanced PET/MR protocol provided cancer staging of children and young adults in less than 1 h with equivalent or superior clinical information compared to clinical standard staging tests. The detection of small pulmonary nodules with PET/MR needs to be improved.
Project description:The aim of the present study was to perform a meta-analysis to assess the diagnostic value of fluorine-18 fluorodeoxyglucose ((18)F-FDG) PET-CT/PET in the pre-operative evaluation of TNM staging in patients with primary colorectal cancer (CRC). The Medline, Embase and Web of Knowledge were searched for studies assessing the diagnostic value of (18)F-FDG PET-CT/PET in the pre-operative evaluation of TNM staging in CRC patients. We pooled the sensitivity, specificity, positive and negative Likelihood ratio (LR+ and LR-) and Diagnostic Odds Ratio (DOR) and constructed summary receiver operating characteristic curves. A total of 28 studies including 2283 CRC patients were analyzed. The pre-operative tumor detecting rate of PET-CT was 95.35%, which was superior to CT (P < 0.05). The pooled sensitivity and specificity of pre-operative T staging by PET-CT/PET was 0.73 (95% CI: 0.65-0.81) and 0.99 (95% CI: 0.98-0.99), which the AUC and Q* were 0.96 and 0.91, respectively. Concerning pre-operative N staging, the pooled sensitivity and specificity of PET-CT/PET were 0.62 and 0.70, which the AUC and Q* were 0.76 and 0.70, respectively. As for M staging, the pooled sensitivity and specificity of PET-CT/PET were 0.91 (95% CI: 0.80-0.96) and 0.95 (95% CI: 0.91-0.98), which the AUC and Q* were 0.96 and 0.91, respectively. (18)F-FDG PET-CT/PET had good performance in the pre-operative tumor detecting rate, T staging and M staging in patients with primary CRC, which might alter the therapeutic strategy. However, the diagnostic value of (18)F-FDG PET-CT/PET in pre-operative N staging in CRC patients was not ideal.
Project description:Background: The objective of this study was to assess the therapeutic and prognostic impact of integrating18F-fluorodeoxyglucose (18-FDG) positron emission tomography (PET)/computed tomography (CT) into work-up (WU) at initial staging of patients with head and neck squamous cell carcinoma (HNSCC). Method: 477 consecutive patients (414M/63F, mean age 62.3 ± 9.7 years) with newly diagnosed HNSCC who underwent pre-treatment 18-FDG PET/CT were retrospectively included. The 18-FDG PET/CT stage (sPET) was compared to the conventional work-up stage (sCWU). A group of cancer specialists determined whether integrating PET/CT into WU at initial staging had an impact on the therapeutic decision, classifying the clinical impact as high (change in therapeutic modality), medium (change in the radiotherapy or surgical procedure), or low (modification of TNM staging and/or detection of synchronous cancer without high or medium impact). Three-year overall survival (OS) was considered as primary endpoint of the prognostic analysis. Results: 18-FDG PET/CT had a clinical impact in 221 patients (46.3%) with a medium or high impact on management in 94 (19.5%) patients. Medium and high impact of 18-FDG PET/CT was statistically equivalent between sCWU-stage I/II and III/IV subgroups (p = 0.02). 42 patients were PET/CT-upstaged from early stage I/II to advanced stage III/IV and had a significantly lower 3-year OS than those with concordant CWU and 18-FDG PET/CT early stage (54.8 vs. 82.6%, p = 0.001). Conclusion: This study demonstrated that implementing 18-FDG PET/CT in the initial WU of HNSCC provides valuable staging information with a better prognostic stratification. Patient management was modified for any disease stage, even for early stage I-II, with consequences on survival.
Project description:The therapeutic approach of gastric cancer strictly depends on TNM staging mainly provided by CT and PET/CT. However, the lymph node size criterion as detected by MDCT causes a poor differential diagnosis between reactive and metastatic enlarged lymph nodes with low specificity values. Our study aims to compare 320-row CT Net enhancement and fluorine-18 fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (F-FDG PET/CT) SUV for N staging of gastric cancer.45 patients with histologically proven gastric cancer underwent CT and F-FDG PET/CT. Two radiologists in consensus evaluated all images and calculated the CT Net enhancement and F-FDG PET/CT SUV for N staging, having the histological findings as the reference standard. CT and F-FDG PET/CT sensitivity, specificity, diagnostic accuracy, positive and negative predictive values (PPV and NPV) were evaluated and compared by using the Mc Nemar test.The histological examination revealed nodal metastases in 29/45 cases (64%). CT Net enhancement obtained sensitivity, specificity, accuracy, PPV and NPV of 90%, 81%, 87%, 90% and 81%, respectively. F-FDG PET/CT SUV obtained sensitivity, specificity, accuracy, PPV and NPV of 66%, 88%, 73%, 90% and 58%, respectively. No statistically significant difference between the two imaging modalities was found (p = 0.1).CT Net enhancement represents an accurate tool for N staging of gastric cancer and could be considered as the CT corresponding quantitative parameter of F-FDG PET/CT SUV. It could be applied in the clinical practice for differentiating reactive lymph nodes from metastatic ones improving accuracy and specificity of CT.
Project description:Our goal was to develop a nomogram by exploiting intratumour heterogeneity on CT and PET images from routine (18)F-FDG PET/CT acquisitions to identify patients with the poorest prognosis.This retrospective study included 116 patients with NSCLC stage I, II or III and with staging (18)F-FDG PET/CT imaging. Primary tumour volumes were delineated using the FLAB algorithm and 3D Slicer™ on PET and CT images, respectively. PET and CT heterogeneities were quantified using texture analysis. The reproducibility of the CT features was assessed on a separate test-retest dataset. The stratification power of the PET/CT features was evaluated using the Kaplan-Meier method and the log-rank test. The best standard metric (functional volume) was combined with the least redundant and most prognostic PET/CT heterogeneity features to build the nomogram.PET entropy and CT zone percentage had the highest complementary values with clinical stage and functional volume. The nomogram improved stratification amongst patients with stage II and III disease, allowing identification of patients with the poorest prognosis (clinical stage III, large tumour volume, high PET heterogeneity and low CT heterogeneity).Intratumour heterogeneity quantified using textural features on both CT and PET images from routine staging (18)F-FDG PET/CT acquisitions can be used to create a nomogram with higher stratification power than staging alone.
Project description:PET/CT has been identified as one of the routine methods for the assessment of multiple myeloma (MM) bone marrow infiltration. In the routine method of performing PET/CT, the 18F-Fludeoxyglucose (18F-FDG) uptake in this disease is often used in the assessment of this condition, however CT diagnosis is not currently commonly used. The aim of the present study was to investigate the importance of CT in PET/CT for assessing diffuse infiltration (DI) of bone marrow in MM. MRI was used as a control in the present study, which is the gold standard for assessing DI of bone marrow and is divided into 3 levels: Mild, moderate and severe DI. Subsequently, a total of four combinations of PET and CT results were listed using the enumeration method for the evaluation of DI in the bone marrow. These combinations were respectively compared with the three levels of MR imaging to screen the most consistent method. The concordances of the new method and routine 18F-FDG PET/CT for the assessment of DI with MR imaging were compared using the McNemar test, respectively. The results of the DI assessment from the two methods were verified by performing Durie-Salmon (D-S) PLUS staging. Compared with MR imaging, the results were as follows: PET and CT exhibited negative results, suggesting mild DI; one of them was positive, suggesting moderate DI; and two were positive, suggesting severe DI. The results of concordance between two methods (new and routine) and MR imaging are indicated as follows: For the new method, McNemar test, P=0.513 and Kappa=0.745; for the routine 18F-FDG PET/CT method, McNemar test, P=0.03 and Kappa=0.547. Re-performance of D-S PLUS staging presented the following results: New method, McNemar test, P=0.317 and Kappa=0.93; for the routine method, McNemar test, P=0.223 and Kappa=0.811. These findings indicated that the CT component of PET/CT could improve the concordance with MRI results in the assessment of DI, and the same results were obtained when D-S PLUS staging was performed. The CT in PET/CT can enhance diagnostic accuracy in the assessment of DI by reducing the false negatives when compared with the routine 18F-FDG method.