Prospective validation of 18F-Fluoroethylcholine as a tracer in PET/MRI for the evaluation of breast lesions and prediction of lymph node status.

PURPOSE: To assess 18F-Fluoroethylcholine (18F-FEC) as a PET/MRI tracer in the evaluation of breast lesions, breast cancer aggressiveness, and prediction of lymph node status. MATERIALS AND METHODS: This prospective, monocentric study was approved by the ethics committee and patients gave written, informed consent. This clinical trial was registered in the EudraCT database (Number 2017-003089-29). Women who presented with suspicious breast lesions were included. Histopathology was used as reference standard. Simultaneous 18F-FEC PET/MRI of the breast was performed in a prone position with a dedicated breast coil. MRI was performed using a standard protocol before and after contrast agent administration. A simultaneous read by nuclear medicine physicians and radiologists collected the imaging data of MRI-detected lesions, including the maximum standardized 18F-FEC-uptake value of breast lesions (SUVmaxT) and axillary lymph nodes (SUVmaxLN). Differences in SUVmax were evaluated with the Mann-Whitney U test. To calculate diagnostic performance, the area under the receiver operating characteristics curve (ROC) was used. RESULTS: There were 101 patients (mean age 52.3 years, standard deviation 12.0) with 117 breast lesions included (30 benign, 7 ductal carcinomas in situ, 80 invasive carcinomas). 18F-FEC was well tolerated by all patients. The ROC to distinguish benign from malignant breast lesions was 0.846. SUVmaxT was higher if lesions were malignant (p < 0.001), had a higher proliferation rate (p = 0.011), and were HER2-positive (p = 0.041). SUVmaxLN was higher in metastatic lymph nodes, with an ROC of 0.761 for SUVmaxT and of 0.793 for SUVmaxLN. CONCLUSION: Simultaneous 18F-FEC PET/MRI is safe and has the potential to be used for the evaluation of breast cancer aggressiveness, and prediction of lymph node status.

Excretion of glucose analogue with SGLT2 affinity predicts response effectiveness to sodium glucose transporter 2 inhibitors in patients with type 2 diabetes mellitus.

PURPOSE: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) regulation, developed as treatment for patients with type 2 diabetes, can be imaged with the glucose analogue alpha-methyl-4-deoxy-4-[18F]fluoro-D-glucopyranoside (Me4FDG), a positron emission tomography (PET) tracer with a high affinity for SGLT1 and SGLT2 proteins. With regard to therapy effectiveness, we aimed to investigate whether clinical parameters or Me4FDG excretion could predict response to SGLT2i in patients with type 2 diabetes. METHODS: In a longitudinal, prospective study, 19 patients with type 2 diabetes underwent Me4FDG combined PET and magnetic resonance imaging (PET/MRI) scans at baseline and 2 weeks after initiation of therapy with SGLT2i, accompanied by the collection of blood and urine samples. Me4FDG-excretion was determined from the Me4FDG uptake in the bladder. Long-term response was determined by HbA1c level after 3 months; a strong response to the therapy was defined as a reduction of HbA1c by at least 10% from baseline. RESULTS: SGLT2i resulted in significantly increased Me4FDG excretion (4.8 vs. 45.0, P < 0.001) and urine glucose (56 vs. 2806 mg/dl, P < 0.001). Baseline urine glucose and baseline Me4FDG excretion correlated both with long-term decline in HbA1c with r = 0.55 (P < 0.05). However, only Me4FDG excretion was a predictor of a strong response to SGLT2i (P = 0.005, OR 1.9). CONCLUSIONS: Using Me4FDG-PET, we demonstrated for the first time renal SGLT2-related excretion before and after short-term SGLT2i treatment. In contrary to other clinical parameters, SGLT2-related excretion before treatment was a robust predictor of long-term HbA1c response in patients with type 2 diabetes, suggesting that therapy effectiveness is only dependent of endogenous SGLT2 processes.

Impact of a content-based image retrieval system on the interpretation of chest CTs of patients with diffuse parenchymal lung disease.

OBJECTIVES: Content-based image retrieval systems (CBIRS) are a new and potentially impactful tool for radiological reporting, but their clinical evaluation is largely missing. This study aimed at assessing the effect of CBIRS on the interpretation of chest CT scans from patients with suspected diffuse parenchymal lung disease (DPLD). MATERIALS AND METHODS: A total of 108 retrospectively included chest CT scans with 22 unique, clinically and/or histopathologically verified diagnoses were read by eight radiologists (four residents, four attending, median years reading chest CT scans 2.1± 0.7 and 12 ± 1.8, respectively). The radiologists read and provided the suspected diagnosis at a certified radiological workstation to simulate clinical routine. Half of the readings were done without CBIRS and half with the additional support of the CBIRS. The CBIRS retrieved the most likely of 19 lung-specific patterns from a large database of 6542 thin-section CT scans and provided relevant information (e.g., a list of potential differential diagnoses). RESULTS: Reading time decreased by 31.3% (p < 0.001) despite the radiologists searching for additional information more frequently when the CBIRS was available (154 [72%] vs. 95 [43%], p < 0.001). There was a trend towards higher overall diagnostic accuracy (42.2% vs 34.7%, p = 0.083) when the CBIRS was available. CONCLUSION: The use of the CBIRS had a beneficial impact on the reading time of chest CT scans in cases with DPLD. In addition, both resident and attending radiologists were more likely to consult informational resources if they had access to the CBIRS. Further studies are needed to confirm the observed trend towards increased diagnostic accuracy with the use of a CBIRS in practice. KEY POINTS: • A content-based image retrieval system for supporting the diagnostic process of reading chest CT scans can decrease reading time by 31.3% (p < 0.001). • The decrease in reading time was present despite frequent usage of the content-based image retrieval system. • Additionally, a trend towards higher diagnostic accuracy was observed when using the content-based image retrieval system (42.2% vs 34.7%, p = 0.083).

Fully Automated, Semantic Segmentation of Whole-Body 18F-FDG PET/CT Images Based on Data-Centric Artificial Intelligence.

We introduce multiple-organ objective segmentation (MOOSE) software that generates subject-specific, multiorgan segmentation using data-centric artificial intelligence principles to facilitate high-throughput systemic investigations of the human body via whole-body PET imaging. Methods: Image data from 2 PET/CT systems were used in training MOOSE. For noncerebral structures, 50 whole-body CT images were used, 30 of which were acquired from healthy controls (14 men and 16 women), and 20 datasets were acquired from oncology patients (14 men and 6 women). Noncerebral tissues consisted of 13 abdominal organs, 20 bone segments, subcutaneous fat, visceral fat, psoas muscle, and skeletal muscle. An expert panel manually segmented all noncerebral structures except for subcutaneous fat, visceral fat, and skeletal muscle, which were semiautomatically segmented using thresholding. A majority-voting algorithm was used to generate a reference-standard segmentation. From the 50 CT datasets, 40 were used for training and 10 for testing. For cerebral structures, 34 18F-FDG PET/MRI brain image volumes were used from 10 healthy controls (5 men and 5 women imaged twice) and 14 nonlesional epilepsy patients (7 men and 7 women). Only 18F-FDG PET images were considered for training: 24 and 10 of 34 volumes were used for training and testing, respectively. The Dice score coefficient (DSC) was used as the primary metric, and the average symmetric surface distance as a secondary metric, to evaluate the automated segmentation performance. Results: An excellent overlap between the reference labels and MOOSE-derived organ segmentations was observed: 92% of noncerebral tissues showed DSCs of more than 0.90, whereas a few organs exhibited lower DSCs (e.g., adrenal glands [0.72], pancreas [0.85], and bladder [0.86]). The median DSCs of brain subregions derived from PET images were lower. Only 29% of the brain segments had a median DSC of more than 0.90, whereas segmentation of 60% of regions yielded a median DSC of 0.80-0.89. The results of the average symmetric surface distance analysis demonstrated that the average distance between the reference standard and the automatically segmented tissue surfaces (organs, bones, and brain regions) lies within the size of image voxels (2 mm). Conclusion: The proposed segmentation pipeline allows automatic segmentation of 120 unique tissues from whole-body 18F-FDG PET/CT images with high accuracy.

Diagnostic Role of PET/CT Tracers in the Detection and Localization of Tumours Responsible for Ectopic Cushing's Syndrome.

BACKGROUND/AIM: Positron emission tomography/computed tomography (PET/CT) plays an important role in cancer localization in ectopic Cushing's syndrome (ECS). However, the choice of the optimal tracer for investigation of this disease is still unclear. We aimed to evaluate the diagnostic feasibility of [18F]fluoro-2-deoxyglucose ([18F]FDG), [18F]fluoro-L-dihydroxyphenylalanine ([18F] FDOPA), and [68Ga]-DOTA-1-Nal3-octreotide ([68Ga]-DOTANOC) in ECS. PATIENTS AND METHODS: All PET/CT scans of patients admitted to our department for suspected ECS between 2010 and 2020 were retrospectively analysed. RESULTS: Collectively, 30 PET/CT examinations, 11 with [18F]FDOPA, 11 with [18F]FDG and 8 with [68Ga]GaDOTANOC were conducted for 18 patients eligible for analysis. [18F]FDG detected the tumour in 3/6 of the cases, [18F]FDOPA in 3/4, and [68Ga]GaDOTANOC in 3/3. [18F]FDOPA was the only tracer without false positive results. CONCLUSION: [68Ga]GaDOTANOC and [18F]FDOPA showed superior results compared to [18F]FDG, although the sensitivity of the tracers might be influenced by the aetiology of the tumour underlying the ECS.

Can supplementary contrast-enhanced MRI of the breast avoid needle biopsies in suspicious microcalcifications seen on mammography? A systematic review and meta-analysis.

PURPOSE: To analyze the rate of potentially avoidable needle biopsies in mammographically suspicious calcifications if supplementary Contrast-Enhanced MRI (CE-MRI) is negative. METHODS: Using predefined criteria, a systematic review was performed. Studies investigating the use of supplemental CE-MRI in the setting of mammographically suspicious calcifications undergoing stereotactic biopsy and published between 2000 and 2020 were eligible. Two reviewers extracted study characteristics and true positives (TP), false positives, true negatives and false negatives (FN). Specificity, in this setting equaling the number of avoidable biopsies and FN rates were calculated. The maximum pre-test probability at which post-test probabilities of a negative CE-MRI met with BI-RADS benchmarks was determined by a Fagan nomogram. Random-effects models, I2-statistics, Deek's funnel plot testing and meta-regression were employed. P-values <0.05 were considered significant. RESULTS: Thirteen studies investigating 1414 lesions with a cancer prevalence of 43.6% (range: 22.7-66.9%) were included. No publication bias was found (P = 0.91). CE-MRI performed better in pure microcalcification studies compared to those also including associate findings (P < 0.001). In the first group, the pooled rate of avoidable biopsies was 80.6% (95%-CI: 64.6-90.5%) while the overall and invasive cancer FN rates were 3.7% (95%-CI: 1.2-6.2%) and 1.6% (95%-CI 0-3.6%), respectively. Up to a pre-test probability of 22%, the post-test probability did not exceed 2%. CONCLUSION: A negative supplementary CE-MRI could potentially avoid 80.6% of unnecessary stereotactic biopsies in BI-RADS 4 microcalcifications at a cost of 3.7% missed breast cancers, 1.6% invasive. BI-RADS benchmarks for downgrading mammographic calcifications would be met up to a pretest probability of 22%.

Soft Tissue Sarcoma Follow-up Imaging: Strategies to Distinguish Post-treatment Changes from Recurrence.

Soft tissue sarcomas encompass multiple entities with differing recurrence rates and follow-up intervals. The detection of recurrences and their differentiation from post-therapeutic changes is therefore complex, with a central role for the clinical radiologist. This article describes approved recommendations. Prerequisite is a precise knowledge of the current clinical management and surgical techniques. We review recurrence rates and treatment modalities. An adequate imaging technique is paramount, and comparison with previous imaging is highly recommended. We describe time-dependent therapy-related complications on magnetic resonance imaging compared with the spectrum of regular post-therapeutic changes. Early complications such as seromas, hematomas, and infections, late complications such as edema and fibrosis, and inflammatory pseudotumors are elucidated. The appearance of recurrences and radiation-associated sarcomas is contrasted with these changes. This systematic approach in follow-up imaging of soft tissue sarcoma patients will facilitate the differentiation of post-therapeutic changes from recurrences.

Whole-Body [18F]FDG-PET/MRI vs. [18F]FDG-PET/CT in Malignant Melanoma.

PURPOSE: To assess the diagnostic performance of simultaneous whole-body 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI) compared to [18F]FDG PET/x-ray computed tomography (CT) for detection of distant metastatic disease in patients with malignant melanoma. PROCEDURES: We included patients with malignant melanoma who underwent a single injection [18F]FDG dual-imaging protocol that included whole-body PET/CT and subsequent whole-body PET/MRI for staging or restaging purposes in a prospective setting. Images from both modalities were analyzed by two rater teams for the presence of metastatic lesions. PET/CT-PET/MRI overall agreement as well as region-based accuracies, sensitivities (Se), and specificities (Sp) were computed. RESULTS: Between July 2014 and December 2018, 22 patients were enrolled. Interrater agreement and overall accuracy (consensus reading) were 78.8 % (95 % CI 71-84.9) and 96.1 % (95 % CI 92.3-98) for PET/MRI and 78 % (70.2-84.3) and 97.4 % (95 % CI 93.7-98.9) for PET/CT, respectively (P = 0.42). PET/MRI reached a region-based Se of 89.1 % (95 % CI 79.4-94.5) and a Sp of 100 %, whereas PET/CT showed a region-based Se of 92.7 % (95 % CI 84-96.9) and a Sp of 100 % for the detection of metastatic disease in malignant melanoma. CONCLUSIONS: Whole-body [18F]FDG-PET/MRI appears to be comparable to [18F]FDG-PET/CT for lesion detection in patients with malignant melanoma.

Assessment of the kidney function parameters split function, mean transit time, and outflow efficiency using dynamic FDG-PET/MRI in healthy subjects.

BACKGROUND: Traditionally, isotope nephrography is considered as the method of choice to assess kidney function parameters in nuclear medicine. We propose a novel approach to determine the split function (SF), mean transit time (MTT), and outflow efficiency (OE) with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) dynamic positron emission tomography (PET). MATERIALS AND METHODS: Healthy adult subjects underwent dynamic simultaneous FDG-PET and magnetic resonance imaging (PET/MRI). Time-activity curves (TACs) of total kidneys, renal cortices, and the aorta were prospectively obtained from dynamic PET series. MRI images were used for anatomical correlation. The same individuals were subjected to dynamic renal Technetium-99 m-mercaptoacetyltriglycine (MAG3) scintigraphy and TACs of kidneys; the perirenal background and the left ventricle were determined. SF was calculated on the basis of integrals over the TACs, MTT was determined from renal retention functions after deconvolution analysis, and OE was determined from MTT. Values obtained from PET series were compared with scintigraphic parameters, which served as the reference. RESULTS: Twenty-four subjects underwent both examinations. Total kidney SF, MTT, and OE as estimated by dynamic PET/MRI correlated to their reference values by r = 0.75, r = 0.74 and r = 0.81, respectively, with significant difference (p < 0.0001) between the means of MTT and OE. No correlations were found for cortex FDG values. CONCLUSIONS: The study proofs the concept that SF, MTT, and OE can be estimated with dynamic FDG PET/MRI scans in healthy kidneys. This has advantages for patients receiving a routine PET/MRI scan, as kidney parameters can be estimated simultaneously to functional and morphological imaging with high accuracy.

A Diagnostic Algorithm That Combines Quantitative 18F-FDG PET Parameters and Contrast-Enhanced CT Improves Posttherapeutic Locoregional Restaging and Prognostication of Survival in Patients With Esophageal Cancer.

PURPOSE: The aim of this study was to determine whether the combination of contrast-enhanced CT (CE-CT) and quantitative F-FDG PET parameters improves locoregional restaging in esophageal cancer (EC) after neoadjuvant therapy. METHODS: Eighty-eight consecutive patients with locally advanced esophageal cancer, who underwent restaging after neoadjuvant chemotherapy or chemoradiotherapy before esophagectomy, were included in this retrospective study. The diagnostic accuracy of CE-CT, visual F-FDG PET/CT (vPET/CT), and quantitative PET parameters was assessed for T and N staging. Histopathology was used as the reference standard. The prognostic value for recurrence-free survival, cancer-specific survival, and overall survival was assessed using Cox regression analysis. RESULTS: Sensitivity, positive predictive value, and accuracy were 78.8%, 70.2%, and 59.0% (CE-CT), and 81.1%, 81.1%, and 68.2% (vPET/CT) for T staging as well as 59.5%, 75.9%, and 50.0% (CE-CT), and 70.2%, 93.7%, and 67.0% (vPET/CT) for N staging, respectively. Tumor length and metabolic tumor volume (MTV) exhibited an incremental increase with advancing T stages (P = 0.002 and 0.038). Contrast-enhanced CT had the highest sensitivity to differentiate advanced T stages (T3/4 vs 0-2; area under the receiver operating curve [AUC], 0.86; P < 0.001), whereas MTV at a threshold of 5.8 mL had the highest sensitivity to detect complete response (T0 vs 1-4; AUC, 0.77; P = 0.002). Contrast-enhanced CT and MTV combined had an even superior accuracy to predict complete response (AUC, 0.82; P < 0.001). The imaging American Joint Committee on Cancer stage provided a better prognostication of recurrence-free survival, cancer-specific survival, and overall survival than either T stage, N stage derived from CE-CT or vPET/CT, or quantitative PET parameters alone. CONCLUSIONS: Combined CE-CT and MTV had the highest diagnostic accuracy to identify the posttherapeutic T stage, allowing for robust prediction of recurrence and survival.

The prognostic value of [123I]-vascular endothelial growth factor ([123I]-VEGF) in glioma.

PURPOSE: Recent studies have shown that tumor vascular endothelial cells and various tumor cells overexpress receptors for vascular endothelial growth factor (VEGF). The aim of this study was to investigate the prognostic value of [123I]-VEGF scintigraphy in patients with histologically verified brain tumors. METHODS: 23 consecutive patients (9 women and 14 men aged 30-83 years, mean age 56.6 ± 14.4 years) with histopathologically-verified primary brain tumors were included in the study. All patients had undergone [123I]-VEGF scintigraphy. SPECT examinations of brain were performed 30 min and 18 h after injection. Additional [11C]-methionine PET ([11C]-MET PET) was performed in eight of the 23 patients. Both [123I]-VEGF and [11C]-MET PET were evaluated visually and semiquantitatively by tumor-to-normal brain uptake ratio (T/N ratio). Thresholds of the T/N ratio were evaluated by analysis of receiver operating characteristics (ROC). Overall survival (OS) was estimated using the Kaplan-Meier method. RESULTS: World Health Organization (WHO) grade IV glioma lesions showed [123I]-VEGF uptake 18 h after the injection, whereas other brain tumors of grade II or III showed negative results. There was no significant difference in the tumor size between VEGF positive and VEGF negative tumors. Patients with [123I]-VEGF T/N ratio threshold <1.32 showed significantly longer survival than patients with T/N ratio ≥ 1.32 (2680 days vs 295 days; P < 0.05). In the subgroup of 16 grade IV glioma patients, significant OS differences were found using a T/N ratio of 1.75 as threshold (T/N ratio < 1.75: 720 days; T/N ≥ 1.75: 183 days; P < 0.05). Significant difference (P < 0.05) was also found in [11C]-MET PET T/N ratios between the grade IV glioma (mean T/N ratio: 3.71) and the grade II or III glioma (mean T/N ratio: 1.74). CONCLUSION: Our results suggest that [123I]-VEGF scintigraphy may be useful for visualization of tumor angiogenesis. In addition, [123I]-VEGF may provide relevant prognostic information in patients with glioma.

Assessing the kidney function parameters glomerular filtration rate and effective renal plasma flow with dynamic FDG-PET/MRI in healthy subjects.

BACKGROUND: A method was developed to assess the kidney parameters glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) from 2-deoxy-2-[18F]fluoro-D-glucose (FDG) concentration behavior in kidneys, measured with positron emission tomography (PET) scans. Twenty-four healthy adult subjects prospectively underwent dynamic simultaneous PET/magnetic resonance imaging (MRI) examination. Time activity curves (TACs) were obtained from the dynamic PET series, with the guidance of MR information. Patlak analysis was performed to determine the GFR, and based on integrals, ERPF was calculated. Results were compared to intra-individually obtained reference values determined from venous blood samples. RESULTS: Total kidney GFR and ERPF as estimated by dynamic PET/MRI were highly correlated to their reference values (r = 0.88/p < 0.0001 and r = 0.82/p < 0.0001, respectively) with no significant difference between their means. CONCLUSIONS: The study is a proof of concept that GFR and ERPF can be assessed with dynamic FDG PET/MRI scans in healthy kidneys. This has advantages for patients getting a routine scan, where additional examinations for kidney function estimation could be avoided. Further studies are required for transferring this PET/MRI method to PET/CT applications.

Change in volume parameters induced by neoadjuvant chemotherapy provide accurate prediction of overall survival after resection in patients with oesophageal cancer.

OBJECTIVES: To assess the prognostic value of volumetric parameters measured with CT and PET/CT in patients with neoadjuvant chemotherapy (NACT) and resection for oesophageal cancer (EC). METHODS: Patients with locally advanced EC, who were treated with NACT and resection, were retrospectively analysed. Data from CT volumetry and (18) F-FDG PET/CT (maximum standardized uptake [SUVmax], metabolic tumour volume [MTV], and total lesion glycolysis [TLG]) were recorded before and after NACT. The impact of volumetric parameter changes induced by NACT (MTVRATIO, TLGRATIO, etc.) on overall survival (OS) was assessed using a Cox proportional hazards model. RESULTS: Eighty-four patients were assessed using CT volumetry; of those, 50 also had PET/CT before and after NACT. Low post-treatment CT volume and thickness, MTV, TLG, and SUVmax were all associated with longer OS (p < 0.05), as were CTthicknessRATIO, MTVRATIO, TLGRATIO, and SUVmaxRATIO (p < 0.05). In the multivariate analysis, only MTVRATIO (Hazard ratio, HR 2.52 [95% Confidence interval, CI 1.33-4.78], p = 0.005), TLGRATIO (HR 3.89 [95%CI 1.46-10.34], p = 0.006), and surgical margin status (p < 0.05), were independent predictors of OS. CONCLUSIONS: MTVRATIO and TLGRATIO are independent prognostic factors for survival in patients after NACT and resection for EC. KEY POINTS: • Change in PET parameters shows close correlation to survival in oesophageal cancer. • Association with OS is independent of changes in SUVmax and CT volume. • Metabolic parameters after NACT correlate with pathologic response and nodal status. • Metabolic parameters may be better suited than SUVmax for response assessment.

Diagnostic accuracy of (18)F-FDG PET/CT compared with that of contrast-enhanced MRI of the breast at 3 T.

PURPOSE: To compare the diagnostic accuracy of prone (18)F-FDG PET/CT with that of contrast-enhanced MRI (CE-MRI) at 3 T in suspicious breast lesions. To evaluate the influence of tumour size on diagnostic accuracy and the use of maximum standardized uptake value (SUVMAX) thresholds to differentiate malignant from benign breast lesions. METHODS: A total of 172 consecutive patients with an imaging abnormality were included in this IRB-approved prospective study. All patients underwent (18)F-FDG PET/CT and CE-MRI of the breast at 3 T in the prone position. Two reader teams independently evaluated the likelihood of malignancy as determined by (18)F-FDG PET/CT and CE-MRI independently. (18)F-FDG PET/CT data were qualitatively evaluated by visual interpretation. Quantitative assessment was performed by calculation of SUVMAX. Sensitivity, specificity, diagnostic accuracy, area under the curve and interreader agreement were calculated for all lesions and for lesions <10 mm. Histopathology was used as the standard of reference. RESULTS: There were 132 malignant and 40 benign lesions; 23 lesions (13.4%) were <10 mm. Both (18)F-FDG PET/CT and CE-MRI achieved an overall diagnostic accuracy of 93%. There were no significant differences in sensitivity (p = 0.125), specificity (p = 0.344) or diagnostic accuracy (p = 1). For lesions <10 mm, diagnostic accuracy deteriorated to 91% with both (18)F-FDG PET/CT and CE-MRI. Although no significant difference was found for lesions <10 mm, CE-MRI at 3 T seemed to be more sensitive but less specific than (18)F-FDG PET/CT. Interreader agreement was excellent (κ = 0.85 and κ = 0.92). SUVMAX threshold was not helpful in differentiating benign from malignant lesions. CONCLUSION: (18)F-FDG PET/CT and CE-MRI at 3 T showed equal diagnostic accuracies in breast cancer diagnosis. For lesions <10 mm, diagnostic accuracy deteriorated, but was equal for (18)F-FDG PET/CT and CE-MRI at 3 T. For lesions <10 mm, CE-MRI at 3 T seemed to be more sensitive but less specific than (18)F-FDG PET/CT. Quantitative assessment using an SUVMAX threshold for differentiating benign from malignant lesions was not helpful in breast cancer diagnosis.

From in†situ to in vivo: an in†situ click-chemistry-derived carbonic anhydrase†II imaging agent for positron emission tomography.

CA II makes a good PET: Discovering positron emission tomography (PET) probes with high target affinities is challenging. PET probe discovery using in situ click chemistry uses (19) F-bearing fragments as (18) F surrogates. This ensures that the lead hits and PET probes have equivalent chemical or biological characteristics, making PET probe discovery predictable and reliable.

Impact of 3,4-dihydroxy-6-18F-fluoro-L-phenylalanine PET/CT on managing patients with brain tumors: the referring physician's perspective.

UNLABELLED: We investigated the impact of (18)F-DOPA brain PET/CT on the clinical management of patients with known or suspected brain tumors. METHODS: A prospective survey of referring physicians was conducted. A pre-PET questionnaire inquired about indication, tumor histology or grade, level of suspicion for tumor recurrence, and planned management. Early post-PET questionnaires asked referring physicians to categorize PET findings as negative, equivocal, or positive; assessed the level of suspicion for primary or recurrent brain tumor; and recorded intended management changes prompted by PET findings. A late follow-up questionnaire 6 mo after the scan aimed at determining patient outcome (recurrence, survival). In addition, all referring physicians were contacted to determine whether management changes intended after (18)F-DOPA PET/CT were implemented. RESULTS: Fifty-eight consecutive patients were included. The clinical suspicion for recurrence increased in 33%, remained unchanged in 50%, and decreased in 17% of patients after adding the PET/CT result to the available diagnostic data. The late post-PET questionnaire confirmed recurrence in 26 patients whereas 32 had stable disease or remained disease-free. (18)F-DOPA PET/CT resulted in intended management changes in 41% of patients. Changes in intended management from wait and watch to chemotherapy (6 patients [25%]) and from chemotherapy to wait and watch (4 patients [17%]) occurred most frequently. Clinical follow-up revealed that 75% of intended treatment changes were implemented. CONCLUSION: (18)F-DOPA PET/CT changed the intended management of 41% of patients with brain tumors, and intended management changes were implemented in 75% of these. These changes suggest a potentially important clinical role of imaging amino acid transport in the management of brain tumor patients.

Human biodistribution and radiation dosimetry of novel PET probes targeting the deoxyribonucleoside salvage pathway.

PURPOSE: Deoxycytidine kinase (dCK) is a rate-limiting enzyme in deoxyribonucleoside salvage, a metabolic pathway involved in the production and maintenance of a balanced pool of deoxyribonucleoside triphosphates (dNTPs) for DNA synthesis. dCK phosphorylates and therefore activates nucleoside analogs such as cytarabine, gemcitabine, decitabine, cladribine, and clofarabine that are used routinely in cancer therapy. Imaging probes that target dCK might allow stratifying patients into likely responders and nonresponders with dCK-dependent prodrugs. Here we present the biodistribution and radiation dosimetry of three fluorinated dCK substrates, (18)F-FAC, L: -(18)F-FAC, and L: -(18)F-FMAC, developed for positron emission tomography (PET) imaging of dCK activity in vivo. METHODS: PET studies were performed in nine healthy human volunteers, three for each probe. After a transmission scan, the radiopharmaceutical was injected intravenously and three sequential emission scans acquired from the base of the skull to mid-thigh. Regions of interest encompassing visible organs were drawn on the first PET scan and copied to the subsequent scans. Activity in target organs was determined and absorbed dose estimated with OLINDA/EXM. The standardized uptake value was calculated for various organs at different times. RESULTS: Renal excretion was common to all three probes. Bone marrow had higher uptake for L: -(18)F-FAC and L: -(18)F-FMAC than (18)F-FAC. Prominent liver uptake was seen in L: -(18)F-FMAC and L: -(18)F-FAC, whereas splenic activity was highest for (18)F-FAC. Muscle uptake was also highest for (18)F-FAC. The critical organ was the bladder wall for all three probes. The effective dose was 0.00524, 0.00755, and 0.00910 mSv/MBq for (18)F-FAC, L: -(18)F-FAC, and L: -(18)F-FMAC, respectively. CONCLUSION: The biodistribution of (18)F-FAC, L: -(18)F-FAC, and L: -(18)F-FMAC in humans reveals similarities and differences. Differences may be explained by different probe affinities for nucleoside transporters, dCK, and catabolic enzymes such as cytidine deaminase (CDA). Dosimetry demonstrates that all three probes can be used safely to image the deoxyribonucleoside salvage pathway in humans.

Correlation of 6-18F-fluoro-L-dopa PET uptake with proliferation and tumor grade in newly diagnosed and recurrent gliomas.

UNLABELLED: 6-(18)F-fluoro-l-dopa ((18)F-FDOPA) measured with PET as a biomarker of amino acid uptake has been investigated in brain tumor imaging. The aims of the current study were to determine whether the degree of (18)F-FDOPA uptake in brain tumors predicted tumor grade and was associated with tumor proliferative activity in newly diagnosed and recurrent gliomas. METHODS: Fifty-nine patients (40 men, 19 women; mean age ± SD, 44.4 ± 12.3 y) with newly diagnosed (n = 22) or recurrent (n = 37) gliomas underwent (18)F-FDOPA PET perioperatively. Tumor tissue was obtained by resection or biopsy in all patients. The tumor grade and Ki-67 proliferation index were obtained by standard pathology assays. Tumor (18)F-FDOPA uptake was quantified by determining various standardized uptake value (SUV) parameters (mean SUV, maximum SUV [SUVmax], mean values of voxels with top 20% SUVs, and tumor-to-normal-brain tissue ratios) that were then correlated with histopathologic grade and Ki-67 proliferation index. RESULTS: Fifty-nine lesions in 59 patients were analyzed. (18)F-FDOPA uptake was significantly higher in high-grade than in low-grade tumors for newly diagnosed tumors (SUVmax, 4.22 ± 1.30 vs. 2.34 ± 1.35, P = 0.005) but not for recurrent tumors that had gone through treatment previously (SUVmax, 3.36 ± 1.26 vs. 2.67 ± 1.18, P = 0.22). An SUVmax threshold of 2.72 differentiated low-grade from high-grade tumors, with a sensitivity and specificity of 85% and 89%, respectively, using receiver-operating-characteristic curve analysis (area under the curve, 0.86). (18)F-FDOPA PET uptake correlated significantly with Ki-67 tumor proliferation index in newly diagnosed tumors (r = 0.66, P = 0.001) but not in recurrent tumors (r = 0.14, P = 0.41). CONCLUSION: (18)F-FDOPA uptake is significantly higher in high-grade than in low-grade tumors in newly diagnosed but not recurrent tumors that had been treated previously. A significant correlation between (18)F-FDOPA uptake and tumor proliferation in newly diagnosed tumors was observed, whereas this correlation was not identified for recurrent tumors. Thus, (18)F-FDOPA PET might serve as a noninvasive marker of tumor grading and might provide a useful surrogate of tumor proliferative activity in newly diagnosed gliomas.

Comparison of CT, PET, and PET/CT for staging of patients with indolent non-Hodgkin's lymphoma.

PURPOSE: The aim was to investigate the potential impact of positron emission tomography (PET)/computed tomography (CT) as compared to PET and CT on the staging of patients with indolent lymphoma. PROCEDURES: PET/CTs from 45 patients with indolent lymphoma undergoing staging or restaging were studied. Clinical follow-up, additional imaging, and histology served as the gold standard. RESULTS: PET/CT correctly diagnosed 92 nodal regions as positive for lymphomatous involvement and 458 as disease free vs 68 and 449 for PET and 64 and 459 for CT, respectively. The respective sensitivities, specificities, and accuracies were 99%, 100%, and 99.8% for PET/CT, 68%, 97.5%, and 92.2% for PET, and 70%, 100%, and 94.7% for CT. PET/CT performed significantly better than PET (p < 0.001 for sensitivity, specificity, and accuracy) and CT (p < 0.001 for sensitivity and accuracy). PET/CT also correctly identified significantly more extra-nodal lesions (22) than CT (14) and PET (nine). CONCLUSIONS: PET/CT provides significantly more accurate information compared to PET and CT for the staging and re-staging of patients with indolent lymphoma.