Potential Utility of FDG PET-CT as a Non-invasive Tool for Monitoring Local Immune Responses

PURPOSE: The tumor microenvironment is known to be associated with the metabolic activity of cancer cells and local immune reactions. We hypothesized that glucose metabolism measured by 2-deoxy-2-(¹⁸F)fluoro-D-glucose (¹⁸F-FDG) positron emission tomography (PET)-computed tomography (CT) (¹⁸F-FDG PET-CT) would be associated with local immune responses evaluated according to the presence of tumor infiltrating lymphocytes (TILs). MATERIALS AND METHODS: We retrospectively reviewed 56 patients who underwent ¹⁸F-FDG PET-CT prior to gastrectomy. In resected tumor specimens, TIL subsets, including cluster of differentiation (CD) 3, CD4, CD8, Forkhead box P3 (Foxp3), and granzyme B, were subjected to immunohistochemical analysis. The prognostic nutritional index (PNI) was calculated as: (10×serum albumin value)+(0.005×peripheral lymphocyte counts). Additionally, the maximum standard uptake value (SUVmax) was calculated to evaluate the metabolic activity of cancer cells. RESULTS: The SUVmax was positively correlated with larger tumor size (R=0.293; P=0.029) and negatively correlated with PNI (R=−0.407; P=0.002). A higher SUVmax showed a marginal association with higher CD3 (+) T lymphocyte counts (R=0.227; P=0.092) and a significant association with higher Foxp3 (+) T lymphocyte counts (R=0.431; P=0.009). No other clinicopathological characteristics were associated with SUVmax or TILs. Survival analysis, however, indicated that neither SUVmax nor Foxp3 held prognostic significance. CONCLUSIONS: FDG uptake on PET-CT could be associated with TILs, especially regulatory T cells, in gastric cancer. This finding may suggest that PET-CT could be of use as a non-invasive tool for monitoring the tumor microenvironment in patients with gastric cancer.

Analysis of 18F-fluorodeoxyglucose positron emission tomography findings in patients with pituitary lesions

BACKGROUND/AIMS: Although magnetic resonance imaging (MRI) is a good visual modality for the evaluation of pituitary lesions, it has limited value in the diagnosis of mixed nodules and some cystic lesions. We evaluated the usefulness of 18F-fluorodeoxyglucose positron emission tomography (FDG PET) for patients with pituitary lesions. METHODS: 18F-FDG PET and MRI were performed simultaneously in 32 consecutive patients with pituitary lesions. The relationships between FDG uptake patterns in PET and MRI findings were analyzed. RESULTS: Of 24 patients with piuitary adenomas, 19 (79.2%) showed increased uptake of 18F-FDG in the pituitary gland on PET scans. All patients with pituitary macroadenomas showed increased 18F-FDG uptake on PET scans. Meanwhile, only five (50%) of the 10 patients with pituitary microadenomas showed positive PET scans. Interestingly, of two patients with no abnormal MRI findings, one showed increased 18F-FDG uptake on PET. For positive 18F-FDG uptake, maximum standardized uptake values (SUVmax) > 2.4 had 94.7% sensitivity and 100% specificity. In addition, SUVmax increased in proportion to the size of pituitary adenomas. Most cystic lesions did not show 18F-FDG uptake on PET scans. CONCLUSIONS: About 80% of pituitary adenomas showed positivity on PET scans, and SUVmax was related to the size of the adenomas. PET may be used as an ancillary tool for detection and differentiation of pituitary lesions.

Quantitative Analysis of Simultaneous EEG Features during PET Studies for Childhood Partial Epilepsy

PURPOSE: To demonstrate the significance of simultaneous electroencephalography (EEG) recording during 2-deoxy-2-[18F] fluoro-D-glucose (FDG)-positron emission tomography (PET) in childhood partial epilepsy. MATERIALS AND METHODS: We included 46 children with partial epilepsy who underwent simultaneous EEG during PET. We compared the epileptogenic area of several EEG features including epileptiform discharges, focal polymorphic slow waves, and electrographic seizures, with the abnormal metabolic region on PET. We also compared the epileptogenic area of simultaneous EEG and PET with findings on magnetic resonance imaging (MRI) and video/EEG, as well as the histopathological diagnosis of the resected cortical area, in eight patients who underwent surgical resection of the epileptogenic area. RESULTS: Hypometabolic regions on interictal PET were concordant with epileptogenic areas of epileptiform discharges and focal polymorphic slow waves, according to their frequency and/or severity, with odds ratios of 1.35 and 1.81, respectively (p<0.05). Hypermetabolic PET was also concordant with epileptogenic areas of ictal events longer than 20 seconds during the period of FDG uptake. Among the eight patients who underwent surgical resection, six patients, including two with non-lesional MRI, had concordant EEG and PET findings, were confirmed pathologically, and became seizure-free after surgery. CONCLUSION: Simultaneous EEG is useful in identifying epileptogenic areas due to a high concordance with abnormal PET metabolic areas. Moreover, simultaneous EEG may also prevent false lateralization of PET from postictal and mixed metabolism during ictal events, as well as abnormal hypermetabolism, during frequent interictal epileptiform discharges.

Imaging of Cancer Metabolism using Positron Emission Tomography

In the 1920's, Warburg reported an observation that cancer cells depend on glycolysis even in the presence of available oxygen likely due to impaired function of mitochondria. Since then, this Warburg s effect has been the most important hypothesis in cancer metabolism and is considered as a seventh hallmark of many human cancers. Aerobic glycolysis was originally attributable to increased bioenergetic needs in rapidly proliferating cancer cells. Recently, biosynthetic aspects of aerobic glycolysis, which reprograms cancer metabolism to synthesize macromolecules such as nucleotides, fatty acids, amino acids, etc., are under active investigation. Introduction of positron emission tomography (PET) and metabolic radiotracers including F-18 flurorodeoxyglucose (FDG) and C-11 acetate made it possible to image cancer metabolism in vivo and to renew the interests on this issue. Studies have found that cancer cells with highly glycolysis features are associated with resistance to many chemotherapeutic regimens and radiation treatment. Therefore, development of glycolytic inhibitors can have an incremental effect to conventional treatments. In addition, functional imaging with metabolic radiotracers will continuously play important roles in detecting cancers and monitoring therapeutic responses to novel anti-metabolic approaches to cancer cells.

Ictal single-photon emission computed tomography with slow dye injection for determining primary epileptic foci in infantile spasms / 소아과

PURPOSE: We investigated whether ictal single-photon emission computed tomography (SPECT) with prolonged injection of technetium-99m (99mTc) ethyl cysteinate dimer during repeated spasms can localize the epileptogenic foci in children with infantile spasms. METHODS: Fourteen children with infantile spasms (11 boys, 3 girls; mean age, 2.2+/-1.3 years) were examined. When a cluster of spasms was detected during video electroencephalography (EEG) monitoring, 99mTc ethyl cysteinate dimer was slowly and continuously injected for 2 minutes to determine the presence of ictal SPECT. For 7 children, the ictal and interictal SPECT images were visually analyzed, while for the remaining 7 children, the SPECT images were analyzed using the subtraction ictal SPECT coregistered to magnetic resonance imaging (MRI) (SISCOM) technique. Subsequently, we analyzed the association between the ictal SPECT findings and those of other diagnostic modalities such as EEG, MRI, and positron emission tomography (PET). RESULTS: Increase in cerebral blood flow on ictal SPECT involved the epileptogenic foci in 10 cases6 cases analyzed by visual assessment and 4 analyzed by the SISCOM technique. The ictal SPECT and video-EEG findings showed moderate agreement (Kappa=0.57; 95% confidence interval, 0.18-0.96). CONCLUSION: Ictal SPECT with prolonged injection of a tracer could provide supplementary information to localize the epileptogenic foci in infantile spasms.

The Result of Evaluation According to Radioactivity of Sequential Sentinel Nodes Biopsy in Breast cancer / 한국유방암학회지

PURPOSE: Radio-guided sentinel node biopsy has become a standard method for evaluating the axillary status. However, there is no guideline for the optimum extent of sentinel lymphadenectomy. The object of this study was to assess the probability of metastases according to the sequence of radioactivity in the sentinel nodes and to determine the accuracy of the methods for evaluating metastases. METHODS: 80 consenting patients underwent sentinel lymph node biopsy using 99mTc-phytate. All the lymph nodes that showed radioactivity higher than surroundings were excised and labeled as SN1 to SN5 according to the sequential radioactivity. All the excised sentinel nodes were evaluated by frozen sectioning (FS) and permanent sectioning (PS). The sensitivity, specificity, negative predictive value and accuracy of the procedure were then analyzed according to the evaluation method. RESULTS: All 80 patients showed a variable number of axillary sentinel node sites (SN1-SN5) and 19 patients (23.8%) had three or more sentinel node sites, with an average number of 1.98. The sensitivity, specificity, NPV and accuracy were higher on PS (94.4%, 100%, 98.4% and 98.8% respectively) than on FS (88.9%, 100%, 96.9% and 97.5% respectively). 20 patients were found to have metastatic breast cancer within the sentinel lymph nodes by IHC, but one case of a metastatic, non-sentinel node was found in the 60 patients with negative sentinel nodes, so that the final false negative rate was 4.8%. In 18 of the 20 sentinel node-positive patients(90.0%), the most radioactive lymph node (SN1) was a positive node. The removal of the most radioactive sentinel node and the 2nd most radioactive sentinel node accurately staged all 20 sentinel node-positive patients. CONCLUSION: Careful evaluation of the sentinel nodes with FS, PS and IHC study is essential to reduce the false negative results. In addition, excision of the highest and the 2nd highest lymph nodes is essential and the excision of the 3rd highest node if any, should also be considered for obtaining a better treatment results.

Comparison of CT and 18F-FDG PET for Detecting Peritoneal Metastasis on the Preoperative Evaluation for Gastric Carcinoma

OBJECTIVE: The aim of our study was to compare the accuracy of CT and 18F-FDG PET for detecting peritoneal metastasis in patients with gastric carcinoma. MATERIALS AND METHODS: One-hundred-twelve patients who underwent a histologic confirmative exam or treatment (laparotomy, n = 107; diagnostic laparoscopy, n = 4; peritoneal washing cytology, n = 1) were retrospectively enrolled. All the patients underwent CT and 18F-FDG PET scanning for their preoperative evaluation. The sensitivities, specificities and accuracies of CT and 18F-FDG PET imaging for the detection of peritoneal metastasis were calculated and then compared using Fisher's exact probability test (p < 0.05), on the basis of the original preoperative reports. In addition, two board-certified radiologists and two board-certified nuclear medicine physicians independently reviewed the CT and PET scans, respectively. A receiver-operating characteristic curve analysis was performed to compare the diagnostic performance of CT and 18F-FDG PET imaging for detecting peritoneal metastasis. RESULTS: Based on the original preoperative reports, CT and 18F-FDG PET showed sensitivities of 76.5% and 35.3% (p = 0.037), specificities of 91.6% and 98.9% (p = 0.035), respectively, and equal accuracies of 89.3% (p = 1.0). The receptor operating characteristics curve analysis showed a significantly higher diagnostic performance for CT (Az = 0.878) than for PET (Az = 0.686) (p = 0.004). The interobserver agreement for detecting peritoneal metastasis was good (κ value = 0.684) for CT and moderate (κ value = 0.460) for PET. CONCLUSION: For the detection of peritoneal metastasis, CT was more sensitive and showed a higher diagnostic performance than PET, although CT had a relatively lower specificity than did PET.

Differential diagnosis of pelvic masses with serum CA-125, ultrasound, and positron emission tomography / 대한산부인과학회지

OBJECTIVE: The purpose of this study was to evaluate whether positron emission tomography (PET) is more valid than transvaginal ultrasonography (TVS) or serum CA125 in differentiating malignant ovarian tumor from benign ovarian tumor. METHODS: Fifty patients with adnexal tumor were evaluated with PET, TVS and serum CA 125 before surgery. PET was used to determine the uptake of FDG (18F-2-fluoro-2-deoxyglucose) for characterization of ovarian tumor. Sassone score was used as sonomorphological scoring system to distinguish from malignant to benign lesion. This scoring system is based on ovarian inner wall structure, wall thickness, septation, and echogenicity. Serum CA-125 levels were measured. After surgery, based on histopathologic findings, sensitivity, specificity, accuracy of each diagnostic modality at each cut-off value were calculated. And the validity of three diagnostic modalities was analysed further with receiver operating characteristics (ROC) curve. RESULTS: In the sonographic evaluation of adnexal tumors, the sensitivity and specificity were 63% and 76% at the cut off level of 9 of Sassone score. With PET, both sensitivity and specificity was not improved respectively. The ROC curves show that PET does not provide statistically significant benefits to predict ovarian malignancy. CONCLUSION: Our results suggested that CA-125 has no statistical significance and PET did not provide more significant additional diagnostic information than TVS for differentiation of malignant ovarian tumor from benign ovarian tumor.

18F-FDG PET and 99mTc-ECD SPECT between Ictal and Interictal Phase in a Patient with Status Epilepticus Arising from the Occipital Lobe

A 35-year-old woman suffered from elementary visual symptom that was confirmed as nonconvulsive simple partial status epilepticus arising from the right occipital lobe. 99mTc-ECD SPECT and 18F-FDG PET were done during the ictal and interictal phase, respectively, which were documented by EEG. Subtraction images of SPECT and PET were overlayed on the MRI by SISCOM to compare the area of metabolic change with that of perfusion change. There was no definite mismatch between the hypermetabolic area and the hyperperfusion area during nonconvulsive status epilepticus.

A Systemic Lupus Erythematosus Patient with Protein Losing Enteropathy

Protein-losing enteropathy (PLE) is a rare manifestation of systemic lupus erythematosus (SLE), and it is an uncommon cause of hypoalbuminemia without proteinuria. We describe a case of an 11 year-old girl who had diarrhea and periorbital edema as the initial symptoms of SLE. PLE was diagnosed by 24-hour stool alpha-1 antitrypsin clearance and 99mTc-human serum albumin scintigraphy.

Neuropsychiatric Lupus Diagnosed by Brain PET: A Case Report / 대한류마티스학회지

Neuropsychiatric lupus is a complication of systemic lupus erythematosus (SLE) characterized by profound metabolic alteration including impaired blood flow, ischemia, decreased aerobic metabolism and progressive neuronal loss of central nervous system. Because of the lack of useful diagnostic methods, it's diagnosis and management is difficult. Recently, F-18- fluoro-2-deoxy-D-glucose positron emission tomography (18FDG-PET) is considered to be a sensitive and reliable method for evaluating SLE patients with neuropsychiatric involvement as compared with brain computed tomography (CT) or magnetic resornance imaging (MRI). In SLE patient having mild or severe neuropsychiatric manifestations, 18FDG-PET shows hypo- or hypermetabolism by different glucose utilization in brain tissue. We experienced a 23-year-old woman with SLE who presented with seizure and loss of consciousness. Initially, brain MRI finding was negative, but brain 18FDG-PET revealed significant hypometabolism in the cerebral hemisphere at active stage of disease and complete resolution of metabolic abnormalities after treatment. Herein, we report a case of neuropsychiatric lupus diagnosed by brain 18FDG-PET.

Recent Advances in Radionuclide Therapy

Radionuclides are naturally occurring unstable atoms that undergo radioactive decay. There are ways of radioactive decay emitting different types of radiation based on their physical properties. Radiation for medical purposes include gamma rays, characteristic X-rays, negative and positive electrons, and alpha particles. Different from external radiotherapy, radionuclide therapy internally delivers therapeutic doses of radiation to the targeted tissue. Historically, P-32 orthophosphate was used for the management of myeloproliferative disorders. I-131 has been used for the treatment of hyperthyroidism as well as thyroid cancer for decades. It is one of the most commonly used therapeutic radionuclides in the current practice and its usefulness has been well established by selectively ablating thyroid tissue. For bone pain by osteoblastic metastases, phosphorus-32, strontium-89, samarium-153, or rhenium-186 could be effectively used in combination with narcotics. Another well known radionuclide therapy is I-131 MIBG for the palliation of patients with inoperable tumors of neural crest origin. In contrast to systemic administration of radioactive materials, local control of malignant tumors could be done by delivering radiation through an intratumoral or intraarterial route. In addition, radioactive skin patch or stent has a promising role in killing skin cancers, esophageal cancer, or malignant biliary strictures. Recently, I-131 or Y-90 conjugated with monoclonal antibodies increases the efficacy of radiation damage to lymphoma tissue employing the targeting effect of monoclonal antibodies. Likewise, radionuclide therapy in combination with gene therapy seems to be promising albeit tumor specific ways of gene delivery should be further investigated. Other possible candidates in radionuclide therapy are radioactive peptides and antisense oligonuclides.

The Role of FDG PET in Malignant Lymphoma / 대한핵의학회잡지

No abstract available.

The Role of FDG PET in Malignant Lymphoma / 대한핵의학회잡지

No abstract available.

A Case of Fraley's Syndrome with Benign Hematuria

Fraley's syndrome is a disorder of vascular impression on the renal infundibulum which is associated with unexplained disabling flank pain, painless microscopic hematuria, and urinary tract infection. We experienced one case of Fraley's syndrome in a 12-year-old girl whose chief complaint was persistent microscopic hematuria. We report this case with a brief review of related literatures.

Osteosarcoma: Correlation of T1 Map and Histology Map

PURPOSE: To determine whether T1 mapping shows regional differences between viable and necrotic regions of osteosarcomas after anticancer chemotherapy and to assess whether this mapping is able to express the characteristics of various intramural tissue components. MATERIALS AND METHODS: Eleven of 20 osteosarcomas were included in this study, while the remaining nine were excluded because the tumor site was inappropriate for comparison of T1 map and tumor macrosection. All patients underwent MR imaging for the purpose of T1 mapping, followed by pre-operative chemotherapy and subsequentl limb-salvage surgery. Spin echo pulse sequencing was used with varying TR (100, 200, 400, 800, 1600, and 2400 msec) and a constant TE of 20 msec. Using a C-language software program, T1 relaxation time was calculated on a pixel-by-pixel basis and then a T1 map was generated by using a post-processing program, NIH Image. We attempted correlation of the T1 map and histologic findings, particularly in regions of interest(ROI) if certain areas were different from other regions on either the T1 or histologic map. Value was expressed as an average of the ratio of T1 of ROI and T1 of fat tissue, and this was used as an internal reference for normalization of the measurement. RESULTS: Tumor necrosis was 100%(Grade IV) in six specimens, and over 90 % (Grade III) in five. Viable tumor cells were found mostly in regions with chondroid matrix and seldom in regions with osteoid matrix. Regardless of cell viability, values ranged from 0.9 to 9.87(mean, 4.02) in tumor necrotic area with osteoid matrices, and from 3.04 to 3.9(mean, 3.55) in areas with chondroid matrices. Other regions with fibrous tissue proliferation, hemorrhage, and fatty necrosis showed values of 2.92-9.83(mean, 7.20), 2.65 -5.96(mean, 3.59), and 1.43 -3.11(mean, 2.68) respectively. The values of various tissues overlapped. No statistically significant difference was found between regions in which tumors were viable and those with tumor necrosis. CONCLUSION: Although we hypothesized that areas of necrotic tumor would show an increased water component(proton number) and would have a longer T1 value than viable tumor tissues, our results were otherwise. Necrotic osteosarcoma tissves showed a wide range of T1 values according to the prevailing tissue components.

Changing Role of Nuclear Medicine for the Evaluation of Focal Hepatic Tumors: From Lesion Detection to Tissue Characterization / 대한핵의학회잡지

The role of scintigraphic imaging has moved from the detection of lesions to the tissue-specific characterization of lesions over the past 2 decades. Major advances in nuclear medicine imaging include: 1) positron imaging, 2) improved instrumentation, such as the use of multidetector (dual or triple head) gamma cameras for single photon emission computed tomography, and 3) development of numerous new radiopharmaceuticals for positron or single photon imaging ( labeled glucose analogue, amino acids, fatty acids, hormones, drugs, receptor ligands, monoclonal antibodies, etc). These advanced have resulted in a significantly improved efficacy of radionuclide techniques for the evaluation of various of focal gepatic tumors is reviewed in this article with an emphasis on the clinical applications of various tracer studies and imaging findings.

The Roles of MR Imaging in Monitoring Therapeutic Effectiveness in Rheumatoid Arthritis: Preliminary Result

PURPOSE: It is difficult to determine objectively therapeutic response in rheumatoid arthritis. This study was carried out in order to assess the feasibility of MR imaging to determine disease status following antirheu-matoid medication. MATERIALS AND METHODS: Eight patients with rheumatoid arthritis underwent MR studies before treatment and approximately one year after the beginning of antirheumatoid medication. Coronal images were obtained, using a T1- and T2-weighted spin echo(n=8), contrast-enhanced T1-weighted images(n=8) and dynamic contrast-enhanced images(n=4). Bone erosions, synovial hypertrophy and bone marrow enhancement in pre- and post-medication studies were compared. On dynamic study, enhancement ratio(E) of pannus was measured(E=SNR at 30sec/SNR at precontrast). Changes of MRI findings and enhancement ratio between pre- and post-medication were compared with disease status as assessed by clinical index. RESULTS: In three patients, improvement of bone marrow edema and synovial hypertrophy was noted, and in addition, there was no evidence of newly developed boneerosion. In two of these patients, complete remission was noted on the basis of the ARA criteria. In another three patients, despite improvement of bone marrow edema and synovial hypertrophy and improved clinical parameters including morning stiffness and ESR, discrete and newly developed bone erosions were noted. In one patient with apoor response to antirheumatoid medication, aggravation of bone marrow edema and synovial hypertrophy was seen, but no definite change in bone erosions was noted. In the remaining one patient, no remarkable changes were seenin bone marrow edema, synovial hypertrophy or bone erosion. Clinically this patient showed no morning stiffness or elevated ESR. The enhancement ratio of pannus decreased in all 4 cases, especially where there were complete remission. CONCLUSION: Synovial extent, bone marrow enhancement, bone erosions and enhancement ratio of pannusmay be good parameters for monitoring disease activity in the follow-up of the patients with rheumatoid arthritis.

The Morphometric Study of the Pons and Cerebellum in Korean using MRI

PURPOSE: To evaluate the size of normal pons and cerebellum in vivo and the change in size according to age, and to compare those with measurement of the diseased pons and cerebellum. MATERIALS AND METHODS: 121 normal adults(M:F=54:67), 5 patients with OPCD and 19 patients with WallerJan degeneration were studied. The normal group was divided into 5 subgroups according to the age (ranged from 20 to 72 years). 1.5T GE Signa MR unit was used. On axial plane, the AP(A) and transverse(B) diameters of the pons, the size of the middle cerebellar peduncle(C), and transverse diameter of the posterior fossa(D) and the cerebellum(E) were measured. On midsagittal plane, the longitudinal(F) and AP(G) diameters of the basis pontis were measured. The ratios of E/D and F/G were calculated. The student t test was used for statistical analysis. RESULTS: C, E and F/G were 15.5mm+/-1.3, 99.8mm+/-4.3 and 1.63+/-.10, respectively. F/G, H/I, and H/J were larger in male(p<.01). All data of the pons showed no statistically significant differences among age groups. E of the seventh decades was shorter than that of the third decades(p<.05). C(12.7 mm+/-1.4) in OPCD and F/G(1. 81+/-.10) in Wallerian degeneration(p<.01) showed the most significant differences when they were compared to the normal. CONCLUSION: Although the cerebellum decreased in size with age, the pons maintained its size up to eighth' decades. The measurement of middle cerebellar peduncle on axial plane (C) and the ratio of basis pontis on midsagittal plane (F/G) were important in the evaluation of OPCD and WallerJan degeneration, respectively.