Discovery and development of brain-penetrant 18F-labeled radioligands for neuroimaging of the sigma-2 receptors

We have discovered and synthesized a series of indole-based derivatives as novel sigma-2 (σ 2) receptor ligands. Two ligands with high σ 2 receptor affinity and subtype selectivity were then radiolabeled with F-18 in good radiochemical yields and purities, and evaluated in rodents. In biodistribution studies in male ICR mice, radioligand [18F]9, or 1-(4-(5,6-dimethoxyisoindolin-2-yl)butyl)-4-(2-[18F]fluoroethoxy)-1H-indole, was found to display high brain uptake and high brain-to-blood ratio. Pretreatment of animals with the selective σ 2 receptor ligand CM398 led to significant reductions in both brain uptake (29%-54%) and brain-to-blood ratio (60%-88%) of the radioligand in a dose-dependent manner, indicating high and saturable specific binding of [18F]9 to σ 2 receptors in the brain. Further, ex vivo autoradiography in male ICR mice demonstrated regionally heterogeneous specific binding of [18F]9 in the brain that is consistent with the distribution pattern of σ 2 receptors. Dynamic positron emission tomography imaging confirmed regionally distinct distribution and high levels of specific binding for [18F]9 in the rat brain, along with appropriate tissue kinetics. Taken together, results from our current study indicated the novel radioligand [18F]9 as the first highly specific and promising imaging agent for σ 2 receptors in the brain.

Development of a highly-specific

As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified

Radical prostatectomy on a 66-year-old patient with a positive 18F-PSMA uptake: Potential application for multiple negative prostate biopsy results

@#The decision to proceed with radical prostatectomy has to be supported with biopsy-proven prostate cancer. However, when a patient has persistently multiple negative prostate biopsies and a high PSA, a serious diagnostic and therapeutic dilemma arises. The PIRADS score generated by the multiparametric-MRI of the prostate provides a guide for a template biopsy using MRI-ultrasound fusion technology, with the hope of minimizing a false negative result. Fluorine-18 Prostate-Specific Membrane Antigen (18F-PSMA) PET CT scan, on the other hand, is used mainly for staging prostate cancer after biochemical recurrence. The use of 18F-PSMA PET CT in the primary clinical diagnosis of prostate cancer has never been reported.The authors performed radical prostatectomy on a 66-year-old HIV-positive male with suspicious lesion on 18F-PSMA, PIRADS 5 on mp-MRI, and a persistently elevated PSA >100 despite multiple negative biopsies. The final histopathological analysis confirmed the presence of adenocarcinoma of the prostate, Gleason 7 (3+4), with negative margins. There were no intraoperative complications, and the patient was discharged in good condition. On follow-up, he had a nadir PSA of 0.058 ng/ml, has partial incontinence, and decreased erectile function and was advised phosphodiesterase inhibitors. 18F-PSMA may be utilized in the decision process for patients who are highly suspected with malignancy but have no preoperatively biopsy-proven cancer after multiple negative biopsies.

Correlation of18F-FDG PET/CT SUVmax value with clinical parameters and biological indicators in patients with lymphoma / 肿瘤

Objective: To evaluate the application value of fluorine-18-fludeoxyglucose (18F-FDG) PET/CT maximal standard uptake (SUVmax) in the diagnosis of lymphoma. Methods: A total of 103 patients with lymphoma which confirmed by pathological diagnosis in Gansu Provincial Hospital from January 2011 to December 2016 were collected. All patients underwent a whole body simultaneous18F-FDG PET/CT and had complete clinical data. The possible relationships of SUVmax with the different pathological subtypes, clinical stages and risk grades of lymphoma were analyzed. The correlations of SUVmax value with Ki-67 index, lactate dehydrogenase (LDH) and erythrocyte sedimentation rate (ESR) were analyzed. Results: There was no significant difference in SUVmax between Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) (P > 0.05). The SUVmax in patients with strongly invasive diffuse large B-cell lymphoma (DLBCL), T-lymphoblastic lymphoma (T-LBL), anaplastic large cell lymphoma (ALCL) and natural killer (NK)/T cell lymphoma was higher than that in patients with relatively weakly invasive mantle cell lymphoma (MCL), peripheral T-cell lymphoma (PTCL), small lymphocytic lymphoma (SLL), follicular lymphoma (FL) (grade 1-2) and marginal zone lymphoma (MZL) (P 0.05). The SUVmax had no significant difference between stage -Ⅱ and III- in the patients with lymphoma (P > 0.05). The SUVmax in the patients with high-risk NHL was higher than that in the patients with intermediate- and low-risk NHL (both P 0.05). Conclusion:18F-FDG PET/CT SUVmax can be used as a reference indicator for evaluating the invasive degree of lymphoma, predicting Ki-67 index, and judging the risk classification of NHL.

Diagnostic Value of Volume-Based Fluorine-18-Fluorodeoxyglucose PET/CT Parameters for Characterizing Thyroid Incidentaloma

OBJECTIVE: To assess clinical value of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) for differentiation of malignant from benign focal thyroid incidentaloma. MATERIALS AND METHODS: This retrospective study included 99 patients with focal thyroid incidentaloma of 5216 non-thyroid cancer patients that had undergone PET/CT. PET/CT semi-quantitative parameters, volume-based functional parameters, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of thyroid incidentaloma were assessed. Receiver-operating characteristic (ROC) analysis was conducted and areas under the curve (AUC) were compared by Hanley and McNeil test to evaluate usefulness of maximum standardized uptake value (SUVmax), MTV and TLG, as markers for differentiating malignant from benign thyroid incidentalomas. RESULTS: Of 99 thyroid incidentalomas, 64 (64.6%) were malignant and 35 (35.4%) were benign. Malignant thyroid incidentalomas were larger (1.8 cm vs. 1.3 cm, p = 0.006), and had higher SUVmax (11.3 vs. 4.8, p 0.05). A threshold TLG 4.0 of 2.475 had 81.3% sensitivity and 94.3% specificity for identifying malignant thyroid incidentalomas. CONCLUSION: Volume-based PET/CT parameters could potentially have clinical value in differential diagnosis of thyroid incidentaloma along with SUVmax.

Selección de un ciclotrón para la producción de radionúclidos de uso en medicina nuclear. Experiencia Cubana / Selection of cyclotron for the production of radionuclides for nuclear medicine. Cuban experience

En el trabajo se ofrecen argumentos para la selección de un ciclotrón de 18 MeV en protones, en su variante Twin. Estará dedicado solo a reacciones nucleares con dichas partículas a los efectos de asegurar el suministro en Cuba de radionúclidos para la tomografía de emisión positrónica (PET) (fundamentalmente ), así como en perspectiva Iodo- para tomografía de emisión de fotón simple (SPECT). Se dan datos que indican la posibilidad de suministrar -FDG al menos a cinco centros PET. Ello posibilitará el acceso de Cuba a una de las más avanzadas tecnología de imagen, el PET/TAC, con el consiguiente beneficio para la atención a pacientes afectados de cáncer y enfermedades cardiovasculares y neurológicas

The work provides arguments for the selection of 18 MeV cyclotron in protons, in its Twin variant. It will be used only for nuclear reactions with these particles in order to ensure the supply of radionuclides in Cuba, for the positron emission tomography ( mainly) as well as for single photon emission computed tomography (, for example), in the future. Data indicating the possibility of supplying -FDG to at least five PET centers are given. This shall allow Cuba to access the one of the most advanced imaging technology, with the consequent benefit for patients suffering from cancer, cardiovascular and neurological diseases

Relationship Between Dual Time Point FDG PET/CTand Clinical Prognostic Indexes in Patients with High Grade Lymphoma: a Pilot Study / 대한핵의학회잡지

PURPOSE: This study investigated the correlative relationship between metabolic parameters estimated from dual time point 2-deoxy-2-[¹⁸F] fluoro-D-glucose (¹⁸F-FDG) positron emission tomography/computerized tomography (PET/CT) and the clinical tools predicting the outcome of a lymphoma. We also measured metabolic and volumetric alterations between early and delayed ¹⁸F-FDG PET/CT in patients with high grade lymphoma (HGL).METHODS: The samples were 122 lymph nodes and extralymphatic lesions from 26 patients diagnosed with HGL. All patients were applied to the International Prognostic Index (IPI), Ann Arbor stage, and revised IPI as clinical prognostic parameters. ¹⁸F-FDG dual time point PET/ CT (DTPFP) consisted of an early scan 1 h after ¹⁸F-FDG injection and a delayed scan 2 h after the early scan. Based on an analysis of DTPFP, we estimated the standardized uptake value (SUV) of tumors from the early and delayed scans, retention index (RI) representing the percentage change between early and delayed SUV, and metabolic volume different index (MVDI) calculated using metabolic tumor volumes (MTV).RESULTS: RI(max) showed a multiple positive correlative relationship with stage and IPI in lesion-by-lesion analysis (p < 0.01). In the case of IPI, the high risk group exhibited higher RI(max) than the low risk group (p = 0.004). In the case of revised IPI, the RI(max) of the low risk group were significantly lower than the intermediate and high risk groups, respectively (p < 0.01). The MVDIs of the best outcome group were decreased in comparison to the moderate outcome group (p = 0.029). There was a significant negative correlative relationship between RI(max) and MVDI, and the inclinations for decreased MVDIs were slightly associated with increased RIs.CONCLUSIONS: RI(max) extracted from DTPFP had a significant relationship to extranodal involvement, staging, IPI, and revised IPI. MVDI showed significant negative correlation with RI(max). Further large scale studies are warranted to support and extend these preliminary results.

Value of 18F-FDG PET-CT in monitoring recurrence and metastasis of small intestinal adenocarcinoma / 肿瘤研究与临床

Objective To evaluate the clinical value of 18F-FDG PET-CT imaging on monitoring recurrence, metastasis and therapeutic decision-making in small intestinal adenocarcinoma patients after radical surgery. Methods Twenty-two patients were enrolled, who underwent surgical operation before received PET-CT scan. PET-CT findings were retrospectively observed to compare with the results of follow-up [postoperative pathology and (or) long-term clinical follow-up]. The roles of PET-CT on therapeutic decision-making were then investigated. Results Among 22 patients, 14 cases were finally diagnosed as recurrence and (or) metastasis, the other 8 cases as disease-free survival after long-term follow-up. According to PET-CT, 13 cases were diagnosed as recurrence and (or) metastasis (including 12 true-positive and 1 false-positive), and 9 cases were negative (including 2 false-negative). The diagnostic sensitivity, specificity, accuracy, positive predictive value and negative predictive value of PET-CT were 85.7 % (12/14), 87.5 % (7/8), 86.4 %(19/22), 92.3%(12/13) and 77.8%(7/9), respectively. The therapeutic decisions were changed in 10 patients (10/22, 45.5 % ) based on PET-CT results. Conclusion 18F-FDG PET-CT has an important clinical value on the detection of recurrence and (or) metastasis of small intestinal adenocarcinoma, which is an ideal method of monitoring.

Tomografia por emissão de pósitrons com FDG-18F na avaliação de pacientes com artrite reumatoide - revisão sistemática / Positron emission tomography with 18F-FDG in the evaluation of patients with rheumatoid arthritis - a systematic review

Introdução A artrite reumatoide (AR) é uma doença caracterizada pela inflamação da membrana sinovial. Diversos autores têm investigado o papel da tomografia por emissão de pósitrons (PET) com flúor-18 (FDG-18F) na AR. Objetivos Revisão sistemática da literatura atual sobre o papel do PET com FDG-18F no diagnóstico, determinação da atividade da doença e avaliação da resposta ao tratamento em pacientes com AR. Métodos Foram realizadas buscas nas bases de dados Medline, Biblioteca Cochrane, Lilacs, Pubmed e Scopus nos idiomas português, inglês e espanhol, utilizando as palavras-chave «artrite reumatoide¼, «sinovite¼, «FDG¼, «PET¼, «metabolismo glicolítico¼ e «atividade da doença¼. Resultados 142 artigos foram inicialmente identificados, dos quais apenas 40 relacionavam-se diretamente ao tema. Foram selecionados 12 artigos originais e três relatos de caso que preenchiam os critérios de inclusão. Discussão A presença de fibroblastos e macrófagos ativados no pannus é responsável pela intensa captação periarticular de FDG-18F. Os padrões de captação não permitem o diagnóstico diferencial com outras artrites. A intensidade de captação e o número de articulações envolvidas são parâmetros metabólicos de atividade da doença que apresentam boa correlação com os índices compostos. Estudos longitudinais de PET têm se mostrado úteis na avaliação da resposta ao tratamento com anti-TNF. Quando realizado precocemente, PET pode predizer a resposta terapêutica. Conclusão Embora o real papel dessa nova técnica na investigação da AR ainda não esteja estabelecido, PET com FDG-18F é uma ferramenta ...

Introduction Rheumatoid arthritis (RA) is a disease characterized by inflammation of the synovial membrane. Several authors have investigated the role of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (18F-FDG) in RA. Objectives To systematically review the current literature on the role of 18F-FDG PET in the diagnosis, determination of disease activity and assessment of treatment response in patients with RA. Methods Searches were conducted in Medline, Cochrane Library, Lilacs, Pubmed and Scopus in Portuguese, English and Spanish languages, using the keywords «rheumatoid arthritis¼, «synovitis¼, «FDG¼, «PET¼, «glycolytic metabolism¼ and «disease activity¼. Results One hundred and forty-two articles were initially identified, of which only 40 were related directly to the subject. Twelve original articles and three case reports that met the inclusion criteria were selected. Discussion The presence of activated macrophages and fibroblasts in pannus are responsible for the intense periarticular uptake of 18F-FDG. The uptake patterns do not allow the differential diagnosis with other arthritides. The uptake intensity and the number of joints involved are metabolic parameters of disease activity that correlate well with the composite indices. Longitudinal studies of PET have proven useful in assessing the response to treatment with anti-TNF. When performed early, PET can predict the therapeutic response. Conclusion Although the actual role of this new technique for the investigation of RA is not yet established, 18F-FDG PET is a promising tool in determining the activity and prediction of response to treatment of patients with RA. .

Evaluation of focal thyroid lesions incidentally detected in fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography images.

Background and Purpose: Increased uptake in the thyroid gland (TG) is often identified as an incidental finding on the whole body fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) in non-thyroid cancer patients. Currently, there is no consensus on the appropriate approach for the management of these cases. Thyroid ultrasound, scintigraphy and fine-needle aspiration biopsy (FNAB) are suggested to exclude malignant thyroid lesions. Our aim is to determine the importance of increased F-18-FDG uptake in the TG on positron emission tomography/computed tomography (PET/CT) scans in patients who are being screened for various forms of non-thyroid cancer. Materials and Methods: We evaluated 2000 cases undergoing whole body PET/CT scanning between April 2011 and October 2012. The age, sex, type of primary cancer, maximum standardized uptake value (SUV max ), size of the thyroid nodules and cervical lymph nodes (CLNs) on 18 F-FDG PET/CT images and if available, the biopsy results were evaluated. Results: In total, 57 patients (23 men, 34 women, mean age ± standard deviation (SD), 60.89 ± 14 years) showed an increased fluorine-18-fluorodeoxyglucose ( 18 F-FDG) uptake by the TG (average SUV max : 4.07 ± 3.7). The CLNs were detected in 19/57 patients (33%). Only 20 cases (35%) received FNAB. The final histopathological diagnosis was papillary thyroid carcinoma in seven patients (mean SUV max ± SD: 6.0 ± 5.43) and benign thyroid disease in seven patients (mean SUV max ± SD: 2.36 ± 0.63). The FNAB results were undetermined for six patients. Conclusion: Focal high 18 F-FDG uptake in the TG may be associated with an increased risk of malignancy, but the clinical significance is unclear. More data are needed to elucidate the role of the SUV in the differentiation of benign and malign thyroid lesions. If a focal increase in 18 F-FDG uptake in the TG on PET/CT is present, a prompt histopathological evaluation should be suggested to clinicians for definitive diagnosis.

Muscular Sarcoidosis Detected by F-18 FDG PET/CT in a Hypercalcemic Patient

Sarcoidosis is a systemic granulomatous disease of unknown etiology that involves many organs, occasionally mimicking malignancy. We herein report a 50-yr-old woman of muscular sarcoidosis of chronic myopathic type, manifested by hypercalcemia and muscle wasting. Besides insignificant hilar lymphadenopathy, her sarcoidosis was confined to generalized atrophic muscles and therefore, F-18 FDG PET/CT alone among conventional imaging studies provided diagnostic clues for the non-parathyroid-related hypercalcemia. On follow-up PET/CT during low-dose steroid treatment, FDG uptake in the muscles disappeared whereas that in the hilar lymph nodes remained. PET/CT may be useful in the evaluation of unexpected disease extent and monitoring treatment response in suspected or known sarcoidosis patients.

FDG PET or PET/CT in Evaluation of Renal Angiomyolipoma

OBJECTIVE: Angiomyolipoma is the most common benign kidney tumor. However, literature describing FDG PET findings on renal angiomyolipoma (AML) is limited. This study reports the FDG PET and PET/CT findings of 21 cases of renal AML. MATERIALS AND METHODS: The study reviews FDG PET and PET/CT images of 21 patients diagnosed with renal AML. The diagnosis is based on the classical appearance of an AML on CT scan with active surveillance for 6 months. The study is focused on the observation of clinical and radiographic features. RESULTS: Six men and 15 women were included in our study. The mean age of the patients was 57.14 +/- 9.67 years old. The mean diameter of 21 renal AML on CT scans was 1.76 +/- 1.00 cm (Min: 0.6 cm; Max: 4.4 cm). CT scans illustrated renal masses typical of AMLs, and the corresponding FDG PET scans showed minimal FDG activities in the area of the tumors. None of the 21 AMLs showed a maximum standardized uptake value (SUVmax) greater than 1.98. No statistically significant correlation was present between SUVmax and tumor size. CONCLUSION: Renal AMLs demonstrate very low to low uptake on FDG PET and PET/CT imaging in this study. When a fat-containing tumor in the kidney is found on a CT scan, it is critical to differentiate an AML from a malignant tumor including an RCC, liposarcoma, and Wilms tumor. This study suggests that FDG PET or PET/CT imaging is useful for differentiating a renal AML from a fat-containing malignant tumor.

A Novel Aromatic Fluorine-18 Labeling Method Using Iodonium Salts Precursor / 핵의학분자영상

As many new drug substances contained various aromatic rings and fluorine attached to an electron rich aromatic ring or on the meta-position, a strategy towards improvement in aromatic fluorination of these compounds is highly desirable. The introduction of fluorine-18 onto aromatic rings showed in the limited condition containing electron withdrawing group (EWG) on the para- or ortho-position to get reasonable radiochemical yield so far. No-carrier added (NCA) [18F]fluoroarene syntheses by iodonium salts recently reported that has the potential to greatly increase the yield in systems or positions that normally not reactive enough to give sufficient yields in simple model reaction. This review describes the methodological approach towards effective aromatic fluorination by diaryliodonium salts and future prospects in an application of novel PET radiotracer.

Avaliação pré-operatória com PET-18F-FDG de nódulos de tireóide com citologia indeterminada / Preoperative evaluation of cytologically indeterminate thyroid nodules with 18F-FDG PET

Esse artigo tem o objetivo de discutir o papel da tomografia por emissão de pósitrons (PET) com 18F-FDG na avaliação pré-operatória de pacientes com nódulos de tireóide com citologia indeterminada. Para o cálculo da sensibilidade, foram selecionados todos os estudos com pacientes com carcinoma de tireóide. Para o cálculo da especificidade, foram selecionados apenas estudos desenhados para avaliação dos pacientes com nódulos com citologia indeterminada. O achado de captação focal na PET-18F-FDG relacionou-se com a presença de carcinoma de tireóide na maioria dos estudos. A sensibilidade do exame foi bastante alta na detecção de malignidade tireoidiana, porém sua especificidade variou de 0 por cento a 66 por cento, sendo de 39 por cento em estudo brasileiro. Concluindo, os estudos indicam que a PET-18F-FDG pode reduzir o número de tireoidectomias desnecessárias em pacientes com nódulos de tireóide com citologia indeterminada. Entretanto, o percentual relativamente elevado de resultados falso-positivos, o alto custo, a baixa disponibilidade do exame em países em desenvolvimento e a pouca experiência clínica ainda limitam o uso da PET-18F-FDG com essa finalidade.

The aim of this article is to discuss the role of 18F-FDG Positron Emission Tomography (PET) in the preoperative evaluation of patients with cytologically indeterminate thyroid nodules. All studies with patients with thyroid cancer were selected to the calculation of sensitivity. Only studies aiming to evaluate patients with thyroid nodules whose cytological result was indeterminate were selected to establish the specificity. The finding of focal 18F-FDG uptake at PET was associated with the presence of thyroid malignancy in most of the studies. The sensitivity of the exam to the detection of thyroid malignancy was extremely high, but the specificity varied from 0 to 66 percent. In our experience, the specificity was 39 percent. In conclusion, the studies suggest that 18F-FDG PET can reduce the number of unnecessary thyroidectomies performed in patients with cytologically indeterminate thyroid nodules. However, the relatively high percentage of false positive results, the high costs, the low availability of this exam in developing countries and the low clinical experience still restrict the use of 18F-FDG PET when recommended with this aim.

Standard test of labelling for efficiency for quality control of no carrier added 90YCL3 / Prueba estándar de la eficiencia del marcaje para el control de la calidad del 90YCI3 sin portador añadido

ABSTRACT Particle emitting radionuclides (e.g. b--emitters 90Y and 177Lu, b-emitter 149Tb, Auger electron emitter 165Er or positron emitter 86Y) are more and more frequently used in research and clinical practice for imaging and radionuclide targeted therapy in nuclear medicine. These radiometals, altogether threevalent lanthanides or actinides with high specific radioactivity, coupled to biomolecule carriers (peptides or monoclonal antibodies) through chelating link (e.g. DTPA or DOTA) bind to specific antigens and/or receptors of diseased tissues, which enables the imaging (positron emitters) or destruction (b--, a-, and Auger electron emitter) of the diseased tissue releasing the antigens or carrying the receptors. The radionuclide precursor 90YCl3 (solution of hard b--emitter 90Y in diluted HCl) with high purity and specific activity is already commercially produced and succesfully used in nuclear medicine, e.g. for radioimmunotherapy (RIT) of Lymphoma. Specification and purity of our product obtained using extraction 90Sr/90Y generator (using technology of centrifuge extractors with di-2-ethylhexylphosphoric acid, D2EHPA) is examined and compared to other similar products in this contribution. A standard method for determination of labelling efficiency of the 90YCl3 precursor based on its reaction with DOTA-Tyr3-Octreotide (DOTA-TOC) and ITLC-SG chromatographic separation is described and proposed for the quality control.

Los radionucleidos emisores de partículas (ej. emisores b 90Y y 177Lu, emisores a 149Tb, emisor de electrones Auger 165Er o emisor de positrones 86Y) se emplean cada vez más en la investigación, en la práctica clínica para el procesamiento de imágenes y en la terapia dirigida de radionuclidos en medicina nuclear. Estos radiometales junto con actínidos o lantánidos trivalentes con alta actividad específica, asociados a portadores de biomoléculas (péptidos o anticuerpos monoclonales) por medio de un enlace con quelatos (ej. DTPA o DOTA) se unen a antígenos específicos receptores de tejidos afectados que permiten el procesamiento de imágenes (emisores de positrones) o la destrucción (b--, a-, y emisores de electrones de Auger) de los tejidos afectados que liberan los antígenos o portan los receptores. El precursor del radionucleido 90YCI3 (solución de emisor b- duro - 90Y en HCI diluido) con elevada pureza y actividad específica ya se produce comercialmente y se usa exitosamente en la medicina nuclear, por ejemplo, para la radioinmunoterapia (RIT) del linfoma. En esta contribución se examina la especificación y la pureza de nuestro producto, obtenido mediante extracción con generador 90Sr/90Y (empleando la tecnología de extractores por centrifugado con ácido di-2-ethylhexyl phosphoric D2EHPA) y se compara con otros productos similares. Se describe y propone para el control de la calidad un método estándar para determinar la eficiencia en el marcaje del precursor del 90YCI3 basado en su reacción con DOTA-Tyr3-ostreotido (DOTA-TOC) y separación cromatográfica ITLC-SG.

A Case with Viral Encephalitis presenting a Dissociations in the Retrograde Amnesia

We describe a case of anterograde and retrograde amnesia resulting from probable herpes simplex encephalitis. In retrograde amnesia, dissociations not only between episodic and semantic memories, but also between semantic memories for personal and public things were observed. We postulated, using FDG-PET, that the former was caused by mesial temporal lesions, based on `multiple trace theory', and the latter, by bilateral lateral temporal lesions, which were probably related to the retrieval of semantic memory, especially for public things.

A Case of Systemic Lupus Erythematosus Presenting with Chorea: Evidence for Striatal Hypermetabolism

Chorea is an uncommon clinical manifestation of Sytemic lupus erythematosus (SLE). Its pathogenic mechanism has not been clearly clarified. We report a 54-year-old woman with SLE who presented with generalized chorea as an initial manifestation. Fluorine-18-fluorodeoxyglucose (FDG) PET revealed increased metabolism in the bilateral putamen. Intravenous and oral administration of steroid markedly improved chorea. Hypermetabolism of the bilateral putamen diminished on follow-up FDG-PET after the disappearance of chorea. This study suggests that chorea in SLE is associated with striatal hypermetabolism.

Correlation of GLUT-1 Expression and F-18-FDG Uptake on Positron Emission Tomography in Breast Carcinoma / 대한암학회지

PURPOSE: Fluorine-18-fluorodeoxyglucose (F-18-FDG) positron emission tomography (PET) has been proven to be useful in the detection of breast cancer. However, the degree of FDG uptake was variable. In this study, we evaluated the relationship between glucose transporter-1 (GLUT-1) expression with the FDG uptake in patients with breast cancer. MATERIALS AND METHODS: 15 patients with proven breast cancer underwent F-18-FDG PET. After surgical resection, anti-GLUT-1 immunohistochemical staining was performed in tumor tissues to measure the GLUT-1 expression. We evaluated the correlation between semi-quantitative FDG uptake by standardized uptake value (SUV) and GLUT-1 expression. RESULTS: In total 15 patients, there was no significant correlation between SUV and GLUT-1 expression. We separated the patients into two groups according to the tumor size. In the group of large tumor (short diameter > or =2 cm), there was no significant correlation. However, in the group of small tumor (short diameter <2 cm), there was a significant correlation between the FDG uptake and GLUT-1 expression (rho=0.812, p=0.047). CONCLUSION: GLUT-1 expression can influence the FDG uptake in the small breast cancers. For large breast cancers, other factors as well as GLUT-1 expression may influence the FDG uptake.

The Usefulness of F-18-FDG PET and The Effect of Scan Protocol in Diagnosis of Intraocular Tumors / 대한핵의학회잡지

PURPOSE: It is important to differentiate malignant from benign lesions of intraocular masses in choosing therapeutic plan. Biopsy of intraocular tumor is not recommended due to the risk of visual damage. We evaluated the usefulness of F-18-FDG PET imaging in diagnosing intraocular neoplasms. MATERIALS AND METHODS: F-l8-FDG PET scan was performed in 13 patients (15 lesions) suspected to have malignant intraocular tumors. There were 3 benign lesions (retinal detachment, choroidal effusion and hemorrhage) and 10 patients with 12 malignant lesions (3 melanomas, 7 retinoblastomas and 2 metastatic cancers). Regional eye images (256*256 and 128*128 matrices) were obtained with or without attenuation correction. Whole body scan was also performed in eight patients (3 benign and 6 malignant lesions). RESULTS: All malignant lesions were visualized while all benign lesions were not visualized. The mean peak standardized uptake value (SUV) of malignant lesions was 2.64+/-0.57 g/ml. There was no correlations between peak SUV and tumor volume. Two large malignant lesions (>1000 mm3 ) showed hot uptake on whole body scan. But two medium-sized lesions (100-l000 mm3) looked faint and two small (<100 mm3) lesions were not visualized. The images reconstructed with 256*256 matrix showed lesions more clearly than those with 128X128 matrix. CONCLUSION: F-18-FDG PET scan is highly sensitivity in detecting malignant intraocular tumor. For the evaluation of small-sized intraocular lesions, whole body scan is not appropriate because of low sensitivity. A regional scan with sufficient acquisition time is recommended for that purpose. Image reconstruction in matrix size of 256*256 produced clearer images than the ones in 128X128, but it does not affect the diagnostic sensitivity.

The Differentiation of Benign from Malignant Soft Tissue Lesions using FDG-PET: Comparison between Semi-quantitative Indices / 대한핵의학회잡지

The purpose of this study is to evaluate the diagnostic accuracy of various quantitative indices for the differentiation of benign from malignant primary soft tissue tumors by FDG-PET. A series of 32 patients with a variety of histologically or clinically confirmed benign (20) or malignant (12) soft tissue lesions were evaluated with emission whole body (5min/bed position) PET after injection of [18F]FDG. Regional 20min transmission scan for the attenuation correction and calculation of SUV was performed in 16 patients (10 benign, 6malignant) followed by dynamic acquisition for 56min. Postinjection transmission scan for the attenuation correction and calculation of SUV was executed in the other 16 patients (10 benign, 6 malignant). The following indices were obtained : the peak and average SUV (pSUV, aSUV) of lesions, tumor-to-background ratio acquired at images of 51 min p.i. (TBR51), tumor-to-background ratio of areas under time-activity curves (TBRarea) and the ratio between the activities of tumor ROI at 51 min p.i. and at the time which background ROI reaches maximum activity on the time-activity curves (T51/Tmax). The pSUV, aSUV, TBR51, and TBRarea, in malignant lesions were significantly higher than those in benign lesions. We set the cut-off values of pSUV, aSUV, TBR51, TBRarea and T51/Tmax for the differentiation of benign and malignant lesions at 3.5, 2.8, 5.1, 4.3 and 1.55, respectively. The sensitivity, specificity and accuracy were 91.7%, 80.0%, 84.4% by pSUV and aSUV, 83.3%, 85.0%, 84.4% by TBR51, 83.3%, 100%, 93.8% by TBRarea and 66.7%, 70.0%, 68.8% by Tsl/Tmax. The time-activity curves did not give additional information compared to SUV or TBR. The one false negative was a case with low-grade fibrosarcoma and all four false positives were cases with inflammatory change on histology. The visual analysis of FDG-PET also detected the metastatic lesions in malignant cases with comparable accuracy. In conclusion, all pSUV, aSUV, TBR51, and TBRarea are useful metabolic semi-quantitative indices with good accuracy for the differentiation of benign from malignant soft-tissue lesions.