Prognostic value of metabolic tumour volume on baseline 18F-FDG PET/CT in addition to NCCN-IPI in patients with diffuse large B-cell lymphoma: further stratification of the group with a high-risk NCCN-IPI.

PURPOSE: The purpose of this study was to determine the prognostic value of metabolic volumetric parameters as a quantitative index on pre-treatment 18F-FDG PET/CT in addition to the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 103 consecutive patients with DLBCL and baseline FDG PET/CT were retrospectively evaluated. Quantitative metabolic parameters, including total metabolic tumour volume (TMTV) using a standardized uptake value (SUV) of ≥2.5 as the threshold, were estimated. Receiver operating characteristic curve analysis was used to determine the optimal cut-off values for the metabolic parameters. The relationships between study variables and patient survival were tested using Cox regression analysis. Patient survival rates were derived from Kaplan-Meier curves and compared using the log-rank test. RESULTS: Median follow-up was 34 months. In patients with a low TMTV (<249 cm3), the 3-year progression free survival (PFS) rate was 83% and the overall survival (OS) rate was 92%, in contrast to 41% and 57%, respectively, in those with a high TMTV (≥249 cm3). In univariate analysis, a high TMTV and NCCN-IPI ≥4 were associated with inferior PFS and OS (P < 0.0001 for all), as was a high total lesion glycolysis (P = 0.004 and P = 0.005, respectively). In multivariate analysis, TMTV and NCCN-IPI were independent predictors of PFS (hazard ratio, HR, 3.11, 95% confidence interval, CI, 1.37-7.07, P = 0.007, and HR 3.42, 95% CI 1.36-8.59, P = 0.009, respectively) and OS (HR 3.41, 95% CI 1.24-9.38, P = 0.017, and HR 5.06, 95% CI 1.46-17.60, P = 0.014, respectively). TMTV was able to separate patients with a high-risk NCCN-IPI of ≥4 (n = 62) into two groups with significantly different outcomes; patients with low TMTV (n = 16) had a 3-year PFS rate of 75% and an OS rate of 88%, while those with a high TMTV had a 3-year PFS rate of 32% and an OS rate of 47% (χ2 = 7.92, P = 0.005, and χ2 = 8.26, P = 0.004, respectively). However, regardless of TMTV, patients with a low-risk NCCN-IPI of <4 (n = 41) had excellent outcomes (3-year PFS and OS rates of 85% and 95%, respectively). CONCLUSION: Pretreatment TMTV was an independent predictor of survival in patients with DLBCL. Importantly, TMTV had an additive prognostic value in patients with a high-risk NCCN-IPI. Thus, the combination of baseline TMTV with NCCN-IPI may improve the prognostication and may be helpful guide the decision for intensive therapy and clinical trials, especially in DLBCL patients with a high-risk NCCN-IPI.

Gray matter correlates of dopaminergic degeneration in Parkinson's disease: A hybrid PET/MR study using (18) F-FP-CIT.

Dopaminergic degeneration is a hallmark of Parkinson's disease (PD), which causes various symptoms affected by corticostriatal circuits. So far, the relationship between cortical changes and dopamine loss in the striatum is unclear. Here, we evaluate the gray matter (GM) changes in accordance with striatal dopaminergic degeneration in PD using hybrid PET/MR. Sixteen patients with idiopathic PD underwent (18) F-FP-CIT PET/MR. To measure dopaminergic degeneration in PD, binding ratio (BR) of dopamine transporter in striatum was evaluated by (18) F-FP-CIT. Voxel-based morphometry (VBM) was used to evaluate GM density. We obtained voxelwise correlation maps of GM density according to the striatal BR. Voxel-by-voxel correlation between BR maps and GM density maps was done to evaluate region-specific correlation of striatal dopaminergic degeneration. There was a trend of positive correlation between striatal BR and GM density in the cerebellum, parahippocampal gyri, and frontal cortex. A trend of negative correlation between striatal BR and GM density in the medial occipital cortex was found. Voxel-by-voxel correlation revealed that the positive correlation was mainly dependent on anterior striatal BR, while posterior striatal BR mostly showed negative correlation with GM density in occipital and temporal cortices. Decreased GM density related to anterior striatal dopaminergic degeneration might demonstrate degeneration of dopaminergic nonmotor circuits. Furthermore, the negative correlation could be related to the motor circuits of posterior striatum. Our integrated PET/MR study suggests that the widespread structural progressive changes in PD could denote the cortical functional correlates of the degeneration of striatal dopaminergic circuits. Hum Brain Mapp 37:1710-1721, 2016. © 2016 Wiley Periodicals, Inc.

Prognostic value of volumetric parameters of (18)F-FDG PET in non-small-cell lung cancer: a meta-analysis.

PURPOSE: We conducted a comprehensive systematic review of the literature on volumetric parameters from (18)F-FDG PET and a meta-analysis of the prognostic value of metabolic tumour volume (MTV) and total lesion glycolysis (TLG) in patients with lung cancer. METHODS: A systematic search of MEDLINE and EMBASE was performed using the keywords "positron emission tomography (PET)", "lung cancer", and "volume". Inclusion criteria were: (18)F-FDG PET used as an initial imaging tool; studies limited to non-small-cell lung cancer (NSCLC); volume measurement of lung cancer; patients who had not undergone surgery, chemotherapy, or radiotherapy before the PET scan; and studies that reported survival data. Event-free survival and overall survival were evaluated as outcomes. The impact of MTV and TLG on survival was measured in terms of the hazard ratio (HR) effect size. Data from each study were analysed using Review Manager 5.2. RESULTS: Thirteen eligible studies including 1,581 patients were analysed. Patients with high MTV showed a worse prognosis with an HR of 2.71 (95% CI 1.82 - 4.02, p < 0.00001) for adverse events and an HR of 2.31 (95% CI 1.54 - 3.47, p < 0.00001) for death. Patients with high TLG also showed a worse prognosis with an HR of 2.35 (95% CI 1.91 - 2.89, p < 0.00001) for adverse events and an HR of 2.43 (95% CI 1.89 - 3.11, p < 0.00001) for death. The prognostic value of MTV and TLG remained significant in a subgroup analysis according to TNM stage as well as the methods for defining cut-off values and tumour delineation. CONCLUSION: Volumetric parameters from (18)F-FDG PET are significant prognostic factors for outcome in patients with NSCLC. Patients with a high MTV or TLG are at higher risk of adverse events and death. MTV and TLG were significant prognostic factors in patients with TNM stage I/II and stage III/IV NSCLC.

Abnormal metabolic connectivity in the pilocarpine-induced epilepsy rat model: a multiscale network analysis based on persistent homology.

Temporal lobe epilepsy is associated with dysfunctional brain networks. Here we investigated metabolic connectivity in the pilocarpine-induced epilepsy rat model and applied a new multiscale framework to the analysis of metabolic networks of small-animal brains. [(18)F]fluorodeoxyglucose PET was acquired in pilocarpine-induced chronic epilepsy rats and controls to yield interregional metabolic correlation by inter-subject manner. When interregional correlation of epilepsy rats and controls was compared directly, the epilepsy rats showed reduced connectivity involving the left amygdala and left entorhinal cortex. When regional graph properties were calculated to characterize abnormal nodes in the epileptic brain network, the epilepsy rats showed reduced nodal and local efficiencies in the left amygdala. Then, a new multiscale framework, persistent brain network homology, was used to examine metabolic connectivity with a threshold-free approach and the difference between two networks was analyzed using single linkage distances (SLDs) of all pairwise nodes. We found a tendency for longer SLDs between the left insula/left amygdala and bilateral cortical/subcortical structures in the epilepsy rats. Persistent brain network homology analysis as well as interregional correlation study implied the abnormal left limbic-paralimbic-neocortical network in the pilocarpine-induced epilepsy rat models. In conclusion, we found a globally disrupted network in the epileptic brain in rats, particularly in the limbic and paralimbic structures by direct comparison, graph properties and multiscale network analysis. These results demonstrate that the multiscale and threshold-free network analysis can be used to find the network abnormality in small-animal brains as a preclinical research.

The effectiveness of recombinant human thyroid-stimulating hormone versus thyroid hormone withdrawal prior to radioiodine remnant ablation in thyroid cancer: a meta-analysis of randomized controlled trials.

We evaluated the efficacy of recombinant human thyroid-stimulating hormone (rhTSH) versus thyroid hormone withdrawal (THW) prior to radioiodine remnant ablation (RRA) in thyroid cancer. A systematic search of MEDLINE, EMBASE, the Cochrane Library, and SCOPUS was performed. Randomized controlled trials that compared ablation success between rhTSH and THW at 6 to 12 months following RRA were included in this study. Six trials with a total of 1,660 patients were included. When ablation success was defined as a thyroglobulin (Tg) cutoff of 1 ng/mL (risk ratio, 0.99; 95% confidence interval, 0.96-1.03) or a Tg cutoff of 1 ng/mL plus imaging modality (RR 0.97; 0.90-1.05), the results of rhTSH and THW were similar. There were no significant differences when ablation success was defined as a Tg cutoff of 2 ng/mL (RR 1.03; 0.95-1.11) or a Tg cutoff of 2 ng/mL plus imaging modality (RR 1.02; 0.95-1.09). When a negative (131)I-whole body scan was used solely as the definition of ablation success, the effects of rhTSH and THW were not significantly different (RR 0.97; 0.93-1.02). Therefore, ablation success rates are comparable when RRA is prepared by either rhTSH or THW.

In vivo visualization and monitoring of viable neural stem cells using noninvasive bioluminescence imaging in the 6-hydroxydopamine-induced mouse model of Parkinson disease.

Transplantation of neural stem cells (NSCs) has been proposed as a treatment for Parkinson disease (PD). The aim of this study was to monitor the viability of transplanted NSCs expressing the enhanced luciferase gene in a mouse model of PD in vivo. The PD animal model was induced by unilateral injection of 6-hydroxydopamine (6-OHDA). The behavioral test using apomorphine-induced rotation and positron emission tomography with [18F]N-(3-fluoropropyl)-2'-carbomethoxy-3'-(4-iodophenyl)nortropane ([18F]FP-CIT) were conducted. HB1.F3 cells transduced with an enhanced firefly luciferase retroviral vector (F3-effLuc cells) were transplanted into the right striatum. In vivo bioluminescence imaging was repeated for 2 weeks. Four weeks after transplantation, [18F]FP-CIT PET and the rotation test were repeated. All 6-OHDA-injected mice showed markedly decreased [18F]FP-CIT uptake in the right striatum. Transplanted F3-effLuc cells were visualized on the right side of the brain in all mice by bioluminescence imaging. The bioluminescence intensity of the transplanted F3-effLuc cells gradually decreased until it was undetectable by 10 days. The behavioral test showed that stem cell transplantation attenuated the motor symptoms of PD. No significant change was found in [18F]FP-CIT imaging after cell transplantation. We successfully established an in vivo bioluminescence imaging system for the detection of transplanted NSCs in a mouse model of PD. NSC transplantation induced behavioral improvement in PD model mice.

18F-FDG PET/CT Evaluation of Thymomas: a Pictorial Review.

The World Health Organization classification divides thymomas according to morphology, epithelial component, and cell atypia. They are grouped into 3 large subgroups: low-risk thymomas (types A, AB, and B1), high-risk thymomas (types B2 and B3), and thymic carcinomas. Tumor subtype represents an independent prognostic factor, which determines therapeutic decision. All thymomas show some degree of 18F-FDG uptake, which tends to increase with the grade of malignancy; this is related to glucose transporter 1 (GLUT1) expression. This review collects all types of thymomas with illustrative images and provides a guide to get familiar with histological characteristics of the lesions and have them in mind because, even imaging findings can overlap among subtypes, certain characteristics can be combined to make an accurate diagnosis based on 18F-FDG PET-CT findings.

Novel use of gamma correction for precise (99m)Tc-HDP pinhole bone scan diagnosis and classification of knee occult fractures.

OBJECTIVE: The aim of this study was to introduce gamma correction pinhole bone scan (GCPBS) to depict specific signs of knee occult fractures (OF) on (99m)Tc-hydroxydiphosphonate (HDP) scan. MATERIALS AND METHODS: Thirty-six cases of six different types of knee OF in 27 consecutive patients (male = 20, female = 7, and age = 18-86 years) were enrolled. The diagnosis was made on the basis of a history of acute or subacute knee trauma, local pain, tenderness, cutaneous injury, negative conventional radiography, and positive magnetic resonance imaging (MRI). Because of the impracticability of histological verification of individual OF, MRI was utilized as a gold standard of diagnosis and classification. All patients had (99m)Tc-HDP bone scanning and supplementary GCPBS. GCPBS signs were correlated and compared with those of MRI. The efficacy of gamma correction of ordinary parallel collimator and pinhole collimator scans were collated. RESULTS: Gamma correction pinhole bone scan depicted the signs characteristic of six different types of OF. They were well defined stuffed globular tracer uptake in geographic I fractures (n = 9), block-like uptake in geographic II fractures (n = 7), simple or branching linear uptake in linear cancellous fractures (n = 4), compression in impacted fractures (n = 2), stippled-serpentine uptake in reticular fractures (n = 11), and irregular subcortical uptake in osteochondral fractures (n = 3). All fractures were equally well or more distinctly depicted on GCPBS than on MRI except geographic II fracture, the details of which were not appreciated on GCPBS. Parallel collimator scan also yielded to gamma correction, but the results were inferior to those of the pinhole scan. CONCLUSIONS: Gamma correction pinhole bone scan can depict the specific diagnostic signs in six different types of knee occult fractures. The specific diagnostic capability along with the lower cost and wider global availability of bone scanning would make GCPBS an effective alternative.

Texture Analysis of F-18 Fluciclovine PET/CT to Predict Biochemically Recurrent Prostate Cancer: Initial Results.

Predicting biochemical recurrence of prostate cancer is imperative for initiating early treatment, which can improve the outcome of cancer treatment. However, because of inter- and intrareader variability in interpretation of F-18 fluciclovine positron emission tomography/computed tomography (PET/CT), it is difficult to reliably discern between necrotic tissue owing to radiation therapy and tumor tissue. Our goal is to develop a computational methodology using Haralick texture analysis that can be used as an adjunct tool to improve and standardize the interpretation of F-18 fluciclovine PET/CT to identify biochemical recurrence of prostate cancer. Four main textural features were chosen by variable selection procedure using least absolute shrinkage and selection operator logistic regression and bootstrapping, and then included as predictors in subsequent logistic ridge regression model for prediction (n = 28). Age at prostatectomy, prostate-specific antigen (PSA) level before the PET/CT imaging, and number of days between the prostate-specific antigen measurement and PET/CT imaging were also included in the prediction model. The overfitting-corrected area under the curve and Brier score of the proposed model were 0.94 (95% CI: 0.81, 1.00) and 0.12 (95% CI: 0.03, 0.23), respectively. Compared with a model with textural features (TI model) and that with only clinical information (CI model), the proposed model achieved 2% and 32% increase in AUC and 8% and 48% reduction in Brier score, respectively. Combining Haralick textural features based on the PET/CT imaging data with clinical information shows a high potential of enhanced prediction of the biochemical recurrence of prostate cancer.

Radiation dosimetry and biodistribution of (99m)Tc-ethylene dicysteine-deoxyglucose in patients with non-small-cell lung cancer.

PURPOSE: To assess the radiation dosimetry and biodistribution of (99m)Tc-labeled ethylene dicysteine deoxyglucose ((99m)Tc-EC-DG) in patients with non-small-cell lung cancer (NSCLC). METHODS: Serial whole-body scans were acquired 0, 2, 4, 6 and 24 h after injection of (99m)Tc-EC-DG (925 MBq) in seven NSCLC patients. Radiation dosimetry, blood clearance and SPECT imaging of the primary tumor were assessed. RESULTS: The critical organ was the bladder wall, with average radiation absorbed dose over all seven patients of 2.47x10(-2) mGy/MBq. The average effective dose equivalent and effective dose were 6.20x10(-3) mSv/MBq (6.89 mSv/1,110 MBq) and 5.90x10(-3) mSv/MBq (6.54 mSv/1,110 MBq), respectively. The primary tumor was visualized with SPECT in six patients. On final pathology, one patient had a granuloma, which did not enhance with (99m)Tc-EC-DG. CONCLUSION: (99m)Tc-EC-DG has acceptable dosimetric and biodistribution properties as a diagnostic tumor-imaging agent. Future studies are planned to evaluate its diagnostic potential.

Imaging and dosimetry of 99mTc EC annexin V: preliminary clinical study targeting apoptosis in breast tumors.

BACKGROUND: Early detection of cellular events is important to predict the outcome of the patients. This study was aimed to use (99m)Tc EC-annexin V to image tumor cells undergoing apoptosis. METHODS: In 10 patients with breast cancer, scintigraphic images and dosimetric estimates were obtained after administering (99m)Tc EC-annexin V. RESULTS: Nine of the 10 cases showed detectable (99m)Tc EC-annexin V uptake in tumor. Higher values of T/N ratios are associated with patient after treatment. CONCLUSIONS: Apoptosis can be quantified using (99m)Tc EC-annexin V.

Noninferiority of 99mTc-Ethylenedicysteine-Glucosamine as an Alternative Analogue to 18F-Fluorodeoxyglucose in the Detection and Staging of Non-Small Cell Lung Cancer.

Objective.99mTc-ethylenedicysteine-glucosamine (99mTc-EC-G) was developed as a potential alternative to 18F-FDG for cancer imaging. A Phase 2 study was conducted to compare 18F-FDG PET/CT and 99mTc-EC-G SPECT/CT in the detection and staging of patients with non-small cell lung cancer (NSCLC). This study was aimed to demonstrate that 99mTc-EC-G SPECT/CT was not inferior to 18F-FDG PET/CT in patients with confirmed NSCLC. Methods. Seventeen patients with biopsy proven NSCLC were imaged with 99mTc-EC-G and 18F-FDG to detect and stage their cancers. Imaging with PET/CT began 45-60 minutes after injection of 18F-FDG. Imaging with 99mTc-EC-G began at two hours after injection (for 5 patients) or three hours (for 12 patients). SPECT/CT imaging devices from the three major vendors of SPECT/CT systems were used at 6 participating study sites. The image sets were blinded to all clinical information and interpreted by independent PET and SPECT expert readers at a central independent core laboratory. Results. 100% concordance between 99mTc-EC-G and 18F-FDG for primary lesion detection, lesion location and size, and confidence that the biopsied lesion was malignant. There was 70% agreement between 99mTc-EC-G and 18F-FDG for metastatic lesion detection, location and size, and confidence that the suspicious lesions were malignant. Conclusions. Evaluation of primary and suspicious metastatic lesions detected by 99mTc-EC-G and 18F-FDG on 17 patients resulted in excellent agreement for detection of primary and metastatic lesions. The study results indicated that 99mTc-EC-G SPECT/CT has the potential to be a clinically viable alternative to 18F-FDG PET/CT and 99mTc-EC-G is not inferior to 18F-FDG PET/CT.

Bone and soft-tissue sarcoma: preoperative staging with fluorine 18 fluorodeoxyglucose PET/CT and conventional imaging.

PURPOSE: To retrospectively compare the diagnostic accuracy of positron emission tomography (PET)/computed tomography (CT), PET, conventional imaging, and combined PET/CT and conventional imaging for tumor staging of bone and soft-tissue sarcomas, by using histologic or follow-up imaging findings as the reference standard. MATERIALS AND METHODS: Institutional review board approval was received for this HIPAA-compliant study; informed consent was obtained. Integrated PET/CT was performed in 117 patients (69 male patients, 48 female patients; mean age, 42 years +/- 21 [standard deviation]; range, 9-86 years). Conventional imaging consisted of magnetic resonance imaging of the primary site, chest radiography, whole-body contrast material-enhanced CT, and bone scintigraphy. A total of four reviewers assessed all images. Overall and T staging were evaluated in 69 (59%) patients who underwent surgical removal of the primary tumors and had pathologically proved results. N and M staging were evaluated in all patients, and their reference methods were based on histologic findings (n = 101) and follow-up CT findings (n = 16). RESULTS: Interpretations based on combined PET/CT and conventional imaging findings correctly staged tumors in 60 (87%) of 69 patients, overstaged tumors in eight (12%) patients, and understaged tumors in one (1%) patient. Overall staging accuracy of combined PET/CT and conventional imaging was significantly higher than that at PET (P < .0001). Combined PET/CT and conventional imaging resulted in correct N staging in 114 (97%) of 117 patients and M staging in 109 (93%) of 117 patients. Combined PET/CT and conventional imaging helped reduce overstaging in three (4%) patients and helped change tumor diagnosis from unresectable to resectable in two (2%) patients compared with PET/CT. CONCLUSION: The combination of PET/CT and conventional imaging is accurate in preoperative staging of bone and soft-tissue sarcoma.

Imaging of neuroendocrine tumors.

Neuroendocrine tumors may arise from a wide range of organs and may occur in various locations in the body. They include carcinoid tumors, paragangliomas (pheochromocytomas), medullary thyroid carcinomas, and islet cell tumors of the pancreas. In this article the authors focus on the more common tumors with origins primarily in the abdomen, namely carcinoid, paraganglioma, and pancreatic islet cell tumors. Imaging assists in delineating the sites and extent of disease, in preoperative planning for resection of the primary tumor and metastatic disease, and in follow-up. Discussion is restricted to the main imaging modalities used in these tumors: cross-sectional imaging, namely CT and MRI, and nuclear medicine studies.

Unsuspected bone and soft tissue lesions identified at cancer screening using positron emission tomography.

BACKGROUND: [F-18]-fluorodeoxy-D-glucose (18FDG) positron emission tomography (PET) is a sensitive modality for detecting malignant lesions. The purpose of the present study was to describe unknown bone and soft tissue lesions in adults identified at cancer screening using PET. METHODS: A total of 4283 individuals of more than or equal to 40 years of age were enrolled. All individuals underwent scans from the base of the skull to proximal thigh. The images were reviewed and a consensus was reached by two board-certified radiologists and a nuclear medicine specialist for the diagnoses. Diagnoses of the lesions were confirmed by histological examination, typical radiologic findings, obvious progression in number and/or size of the lesion on follow-up examinations, and medical examination of interview. RESULTS: Unsuspected focal abnormality in the bone and soft tissue were found in 62 individuals (1.4%). The mean size of the lesion was 26 mm (range, 6-155 mm). There were 29 bone lesions (47%) and 33 soft tissue lesions (53%). A malignant lesion was found in one case (1.6%) and histologic diagnosis was primary non-Hodgkin lymphoma of the vertebra. Other major diagnoses were healing bone (n = 11, 18%) and benign cystic lesions of bone and soft tissue (n = 9, 15%), and brown fat of soft tissue (n = 4, 6%). CONCLUSION: Unsuspected bone and soft tissue lesions of a wide variation of pathologic and clinical diagnoses were encountered at cancer screening using PET. Correlation with clinical history and other imaging findings is essential in the differential diagnosis.

Magnetic resonance screening trial for hepatic metastasis in patients with locally controlled choroidal melanoma.

OBJECTIVE: The aim of the present study was to evaluate the value of magnetic resonance (MR) screening for detection of hepatic metastasis in patients with locally controlled choroidal melanoma. METHODS: MR examinations were performed after an initial diagnosis of choroidal melanoma in 159 patients (mean age 56 years: range, 10-86 years). The MR follow-up interval was 5.2 +/- 1.7 years (range, 1.2-6.6 years). A total of 363 MR studies were reviewed by two radiologists for predominant signal intensity characteristics. Hepatic metastasis was verified by histological examination: tumor resection and CT-guided needle biopsy specimens and/or on the basis of an obvious progression in number and/or size of the lesions on the follow-up MR examination. RESULTS: The majority of patients underwent MR examinations from one to three times (n = 126, 79%). During a mean follow-up period of 5.7 years, a focal abnormality in the liver was found in 20 patients (13%). Of these, 15 patients (9%) were diagnosed as having hepatic metastasis. The number of the metastatic lesions with a short T1 and short T2 pattern were one (n = 1, 9%), two (n = 2, 18%), three (n = 1, 9%) and multiple (n = 7, 63%). The focal abnormalities of MR examinations in five other patients consisted of vascular artifacts (n = 3, 15%) and cysts with hemorrhage (n = 2, 10%). CONCLUSIONS: The screening of MR examinations detected hepatic metastasis in 15 of 159 patients (9%) with locally controlled choroidal melanoma.

Functional imaging of estrogen receptors with radiolabeled-GAP-EDL in rabbit endometriosis model.

RATIONALE AND OBJECTIVES: Endometriosis is a common women's health problem. Animal models provide an invaluable tool to study the natural history of endometriosis. We previously have reported that (99m)Tc-labeled glutamate peptide-estradiol ((99m)Tc-GAP-EDL) is a useful agent for imaging functional estrogen receptor (ER) via an ER-mediated process. This study was to evaluate the feasibility of using radiolabeled GAP-EDL to image ER-positive (ER +) endometriosis in nonprimate animal models. MATERIALS AND METHODS: 3-Aminoethyl estradiol (EDL) was conjugated to glutamate peptide (GAP) to yield GAP-EDL. In vitro cellular uptake studies of (99m)Tc and (68)Ga-GAP-EDL inhibition with cold estrone were conducted in 13,762 rat mammary tumor cells. To create a rabbit model with endometriosis, part of uterine tissue was dissected and grafted in the peritoneal wall. Eight weeks after surgery, scintigraphic images were obtained after intravenous injection of (99m)Tc-GAP-EDL (1 mCi/rabbit, intravenous) at 0.5-2.0 hours, and (68)Ga-GAP-EDL at 45 minutes. We also performed (68)Ga-GAP-EDL blocking study in rabbit model by using tamoxifen. The rabbits were sacrificed and the grafts were excised for histologic examination. RESULTS: In vitro uptake study of (99m)Tc- and (68)Ga-GAP-EDL in 13,762 rat breast cancer cells showed gradually increasing uptake of both tracers. Accumulation of (68)Ga-GAP-EDL in 13,762 cells was inhibited with cold estrone in a dose-dependent manner. In the endometriosis model, the grafted uterine tissue could be visualized by (99m)Tc-GAP-EDL. Necropsy was performed at 2.5 hours after injection time. Four follicular endometrial lesions in eight implanted endometrial tissues were detected, and all lesions could be detected by (99m)Tc-GAP-EDL. Planar scintigraphy of uterus, ovary and implants of necropsy specimen revealed an increased uptake of (99m)Tc-GAP-EDL in comparison with surrounding abdominal wall tissue. Microscopic examinations support that (99m)Tc-GAP-EDL was accumulated in the microinvasive endometrial tissue. After blocking with tamoxifen, (68)Ga-GAP-EDL accumulation in the endometrial grafts could not be visualized, and endometrial tissue-to-normal tissue count ratios were statistically higher in a nonblocked image than that in the blocked image. CONCLUSIONS: Endometriosis uptake of radiolabeled GAP-EDL was via an estrogen receptor-mediated process. Radiolabeled-GAP-EDLs are useful agents for imaging endometriosis.

Evaluation and localization of lymphatic drainage and sentinel lymph nodes in patients with head and neck melanomas by hybrid SPECT/CT lymphoscintigraphic imaging.

In patients with head and neck tumors, preoperative lymphoscintigraphy can be used to map lymphatic drainage patterns and identify sentinel lymph nodes. However, it is very difficult to determine the exact locations of head and neck sentinel nodes on preoperative lymphoscintigraphy without the use of anatomic landmarks. Lymph nodes in the head and neck are grouped into 7 regions, or levels, on the basis of anatomic landmarks. In patients undergoing standard lymphoscintigraphy, obtaining lateral marker images that show important anatomic landmarks can help with the localization of sentinel nodes. However, technical problems often render marker images of little or no use. Hybrid SPECT/CT lymphoscintigraphic imaging facilitates the localization of sentinel nodes by reliably showing the relationships between sentinel nodes and important anatomic structures. After reading this article, the reader should understand the lymph node level classification system for head and neck melanomas, be able to describe the technique used for the imaging of sentinel nodes in the head and neck region, and be able to demonstrate how SPECT/CT lymphoscintigraphic imaging can enable precise sentinel node localization and thus help to ensure minimal dissection.

Bilateral Renal Metastasis of Hürthle Cell Thyroid Cancer with Discordant Uptake Between I-131 Sodium Iodide and F-18 FDG.

Renal metastasis of thyroid cancer is extremely rare. We report the case of a 62-year-old woman with Hürthle cell thyroid cancer (HCTC) with lungs, bones, and bilateral kidneys metastases. The renal metastatic lesions were clearly demonstrated by 131I whole body scan (WBS) with SPECT/CT. However, they exhibited false-negative results in 18F-FDG PET/CT, kidney ultrasonography, and contrast-enhanced CT scan. The findings imply that tumors have low glucose metabolism and are able to accumulate radioiodine, which is not commonly found in the relatively aggressive nature of HCTC. The patient received two sessions of 200 mCi 131I therapy within 6 months duration. There was complete treatment response as evaluated by the second post-therapeutic 131I SPECT/CT and serum thyroglobulin. To our knowledge, renal metastasis from HCTC with positive 131I but negative 18F-FDG uptake has not been reported in the literature. This case suggests that 131I SPECT/CT is useful for lesion localization and prediction of 131I therapy response.

Clinical Significance of Pretreatment FDG PET/CT in MIBG-Avid Pediatric Neuroblastoma.

PURPOSE: 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging is well known to have clinical significance in the initial staging and response evaluation of the many kinds of neoplasms. However, its role in the pediatric neuroblastoma is not clearly defined. In the present study, the clinical significance of FDG-PET/computed tomography (CT) in 123I- or 131I-metaiodobenzylguanidine (MIBG)-avid pediatric neuroblastoma was investigated. METHODS: Twenty patients with neuroblastoma who undertook pretreatment FDG PET/CT at our institute between 2008 and 2015 and showed MIBG avidity were retrospectively enrolled in the present study. Clinical information-including histopathology, and serum markers-and several PET parameters-including SUVmax of the primary lesion (Psuv), target-to-background ratio (TBR), metabolic tumor volume (MTV), and coefficient of variation (CV)-were analyzed. The prognostic effect of PET parameters was evaluated in terms of progression-free survival (PFS). RESULTS: Total 20 patients (4.5 ± 3.5 years) were divided as two groups by disease progression. Six patients (30.0 %) experienced disease progression and one patient (5.0 %) died during follow-up period. There were not statistically significant in age, stage, MYCN status, primary tumor size, serum lactate dehydrogenase (LDH), neuron-specific enolase (NSE), and ferritin level between two groups with progression or no progression. However, Psuv (p = 0.017), TBR (p = 0.09), MTV (p = 0.02), and CV (p = 0.036) showed significant differences between two groups. In univariate analysis, PFS was significantly associated with Psuv (p = 0.021) and TBR (p = 0.023). CONCLUSIONS: FDG-PET parameters were significantly related with progression of neuroblastoma. FDG-PET/CT may have the potential as a valuable modality for evaluating prognosis in the patients with MIBG-avid pediatric neuroblastoma.