The application of positron emission tomography in the research and development of central nervous system drugs / 中国临床药理学与治疗学

Positron emission tomography (PET) now plays an important role in the research and development (R&D) of central nervous system (CNS) drugs. PET could characterize the biodistribution, pharmacokinetics, and receptor binding of CNS drugs quantitatively. The present review summarized the quantitative methods of PET used in the pharmacokinetics and receptor occupancy analysis of CNS drugs. Moreover, the present review listed various applications of PET supporting R&D of CNS drugs, which could provide a new direction for the R&D of CNS drugs.

Progress in diagnosis and treatment of hepatic alveolar echinococcosis / 器官移植

Hepatic echinococcosis is a chronic parasitic disease, which is caused by the larvae of Echinococcus multilocularis. It has a high risk of disability and mortality, which is also known as "parasite cancer". In clinical practice, hepatic echinococcosis can be divided into hepatic alveolar echinococcosis and hepatic cystic echinococcosis. Hepatic echinococcosis is widely prevalent worldwide. It mainly occurs in the populations residing agricultural and pastoral areas in western China, posing significant threats to the quality of life of local residents. At present, surgery is the main treatment for hepatic echinococcosis in clinical settings. With rapid development of surgical diagnosis and treatment technology and deepening understanding of hepatic echinococcosis, diagnosis and treatment regimens have also been constantly improved. In this article, research progresses on the diagnosis and treatment of hepatic alveolar echinococcosis were reviewed, aiming to provide reference for clinicians, deliver early diagnosis and treatment, mitigate adverse effects of this disease upon patients and improve clinical prognosis.

Evolução da Captação Miocárdica de 18F-FDG em Paciente com Diagnóstico de Cardiotoxicidade / Progression of Myocardial 18F-FDG Uptake in a Patient with Cardiotoxicity

Resumo O objetivo deste relato é mostrar a evolução da cardiotoxicidade (CTX) por quimioterápicos em paciente com linfoma por exames de imagens, destacando a importância da captação miocárdica de flúor-18 fluordeoxiglicose (18F-FDG) pela tomografia por emissão de pósitrons, acoplada à tomografia computadorizada (PET/CT). Feminino, 43 anos, com linfoma uterino, submetida a histerectomia, três esquemas de quimioterapia (QT), sucessivamente, e radioterapia. Apresentou episódios de insuficiência cardíaca aguda dois anos após QT. Ecocardiograma mostrou redução da fração de ejeção do ventrículo esquerdo (FEVE). Análise retrospectiva do 18F-FDG PET/CT observou elevação da captação miocárdica em todos os exames durante o seguimento oncológico. Apesar da remissão oncológica, a paciente desenvolveu IC com FEVE reduzida. Durante a QT, ocorreu aumento difuso e significativo da captação miocárdica de 18F-FDG, que precedeu a queda do desempenho cardíaco, e pareceu refletir alterações metabólicas nos cardiomiócitos relacionadas à CTX. A análise da captação miocárdica de 18F-FDG modificaria o desfecho cardiológico da paciente? Esse questionamento é relevante, visto que outros pacientes podem se beneficiar desse método como marcador precoce de CTX. Os exames de imagem são imprescindíveis no acompanhamento de pacientes com risco de CTX. O ecocardiograma permanece como principal auxílio diagnóstico, porém o 18F-FDG PET/CT pode estar surgindo como uma poderosa ferramenta para um diagnóstico mais precoce dessa condição clínica.

Abstract The objective of this case report was to present the progression of chemotherapy-induced cardiotoxicity in a patient with lymphoma, highlighting the importance of myocardial fluor-18-fluorodeoxyglucose (18F-FDG) uptake by positron emission tomography coupled with computed tomography (PET/CT). 43-year-old female patient with uterine lymphoma, who underwent hysterectomy followed by three chemotherapy regimens and radiotherapy. The patient had episodes of acute heart failure two years after chemotherapy. Echocardiogram revealed a reduction in left ventricular ejection fraction (LVEF). A retrospective analysis of 18F-FDG PET/CT showed an increase in myocardial uptake in all tests performed during oncologic treatment. Despite disease remission, the patient developed heart failure with reduced LVEF. During chemotherapy, there was a diffuse, significant increase in myocardial 18F-FDG uptake, which preceded the decrease in myocardial performance and seemed to reflect metabolic changes in cardiomyocytes, related to cardiotoxicity. Would an analysis of myocardial 18F-FDG uptake yield a different cardiac outcome in this patient? This question is relevant, considering that other patients may benefit from the use of PET as an early marker of cardiotoxicity. Imaging tests are essential in the follow-up of patients at risk of cardiotoxicity. Although echocardiography remains the main imaging test in the diagnosis of cardiotoxicity, 18F-FDG PET/CT may be a powerful tool for the early diagnosis of this condition.

Implementation of positron emission tomography with 18F-fluorodeoxyglucose associated with computed tomography in patients with sarcoidosis. Its effect on disease staging and the therapeutic approach

Objetives: to evaluate the benefit of implementing 18F-FDG PET/TC in the staging and treatment adjustment of patients with sarcoidosis, compared with the signs and symptoms and complementary test results usually employed. Materials and methods: an observational, analytical electronic chart review of a retrospective cohort of patients seen for sarcoidosis in the internal medicine department of a Spanish university hospital. Results: a total of 31 patients (18 males) were evaluated, with an average age of 54.6±14.71 years and 11±5.75 years since their sarcoidosis diagnosis. In the 84.6% of the reviews, positive uptake was objectified on the 18F-FDG PET/TC. In the 42.3% of the occasions, the objectified find ing allowed restaging of the patient. The 18F-FDG PET/TC result justified the choice of treatment in the 71% of the reviews. Conclusions: 18F-FDG PET/TC provided additional advantages in the staging and therapeutic management of patients with sarcoidosis, compared with the evaluation of signs and symptoms and other clinical tests usually employed in follow up, due to its greater accuracy in determining the activity and extension of the disease. (Acta Med Colomb 2022; 48. DOI: https://doi.org/10.36104/amc.2023.2778).

Colonoscopy following the positron emission tomography/computed tomography scan in patients with incidental colorectal uptake: what is the most effective management?

SUMMARY OBJECTIVE: Colorectal cancer is one of the most common malignancies. Survival rates are directly related to the stage of cancer at the time of diagnosis, emphasizing the value of early diagnosis. Positron emission tomography with 18F-fluorodeoxyglucose is the gold standard imaging technique in staging, monitoring after treatment, and follow-up. We aimed to assess the importance of incidental 18F-fluorodeoxyglucose uptake by colon and rectum in positron emission tomography-computed tomography imaging to determine a significant cutoff value for further investigation using colonoscopy and histopathological assessment. METHODS: We performed a retrospective analysis of patients with both 18F-fluorodeoxyglucose-positron emission tomography/computed tomography scan and colonoscopy during 1 year and included the cases who had undergone a colonoscopy within 3 months following the positron emission tomography/computed tomography scan due to an incidental positive finding. Patients with a diagnosed colorectal malignancy or with a history of previous colorectal operations were excluded. RESULTS: A total of 81 patients were included in this study. Among 81 colonoscopic evaluations, histopathology revealed malignancy in 8 patients, and the prevalence of incidental colorectal cancer 18F-fluorodeoxyglucose uptake was found to be 9.87%. SUVmax was found to be significantly related to malignancy and other colonoscopic findings (p<0.001). SUVmax cutoff value to suggest colorectal cancer was found to be median [7.9 (4.1-12.7)] (p<0.001). CONCLUSION: Regarding the studies determining a significant cutoff value, incidental colonic 18F-fluorodeoxyglucose uptake on positron emission tomography/computed tomography should lead the clinician to further investigation with colonoscopic biopsy, although the cutoff values for SUVmax are not certain and different in almost every published study, and negative positron emission tomography.computed tomography findings should not completely rule out malignancy, especially in high-risk patients.

Brain glucose metabolism and gray matter volume in retired professional soccer players: a cross-sectional [18F]FDG-PET/MRI study / Metabolismo glicolítico cerebral e volume de substância cinzenta em jogadores de futebol profissionais aposentados: um estudo transversal de [18F]FDG-PET/RM

Abstract Background Professional soccer athletes are exposed to repetitive head impacts and are at risk of developing chronic traumatic encephalopathy. Objective To evaluate regional brain glucose metabolism (rBGM) and gray matter (GM) volume in retired soccer players (RSPs). Methods Male RSPs and age and sex-matched controls prospectively enrolled between 2017 and 2019 underwent neurological and neuropsychological evaluations, brain MRI and [18F]FDG-PET in a 3.0-Tesla PET/MRI scanner. Visual analysis was performed by a blinded neuroradiologist and a blinded nuclear physician. Regional brain glucose metabolism and GM volume were assessed using SPM8 software. Groups were compared using appropriate statistical tests available at SPM8 and R. Results Nineteen RSPs (median [IQR]: 62 [50-64.5] years old) and 20 controls (60 [48-73] years old) were included. Retired soccer players performed worse on mini-mental state examination, digit span, clock drawing, phonemic and semantic verbal fluency tests, and had reduced rBGM in the left temporal pole (pFDR = 0.008) and the anterior left middle temporal gyrus (pFDR = 0.043). Semantic verbal fluency correlated with rBGM in the right hippocampus, left temporal pole, and posterior left middle temporal gyrus (p ≤ 0.042). Cray matter volume reduction was observed in similar anatomic regions but was less extensive and did not survive correction for multiple comparisons (pFDR ≥ 0.085). Individual [18F]FDG-PET visual analysis revealed seven RSPs with overt hypometabolism in the medial and lateral temporal lobes, frontal lobes, and temporoparietal regions. Retired soccer players had a higher prevalence of septum pellucidum abnormalities on MRI. Conclusion Retired soccer players had reduced rBCM and CM volume in the temporal lobes and septum pellucidum abnormalities, findings possibly related to repetitive head impacts.

Resumo Antecedentes Jogadores profissionais de futebol estão expostos a impactos cranianos repetitivos e ao risco de desenvolver encefalopatia traumática crônica. Objetivo Avaliar o metabolismo glicolítico cerebral regional (MCCr) e o volume de substância cinzenta (vSC) em jogadores de futebol aposentados (JFAs). Métodos Jogadores de futebol aposentados masculinos e controles pareados por idade e sexo foram incluídos prospectivamente entre 2017 e 2019. Foram realizadas avaliações neurológica e neuropsicológica, ressonância magnética (RM) e [18F]FDG-PET cerebrais (3.0-Tesla PET/RM). As imagens foram analisadas visualmente por um neurorradiologista e um médico nuclear cegos ao grupo de cada participante. O metabolismo glicolítico cerebral regional e o vSC foram avaliados através do programa SPM8. Os grupos foram comparados através de testes estatísticos apropriados disponíveis em SPM8 e R, de acordo com a distribuição e o tipo dos dados. Resultados Dezenove JFAs (mediana [IIQ]: 62 [50-64.5] anos) e 20 controles (60 [48-73] anos) foram incluídos. Os JFAs tiveram pior desempenho no mini-exame do estado mental e nos testes de dígitos, desenho do relógio, fluência verbal e fluência semântica e apresentaram MCCr significativamente reduzido no polo temporal e no giro temporal médio anterior esquerdos. Fluência semântica (animais) apresentou correlação positiva com MCCr no hipocampo direito, no polo temporal esquerdo e no aspecto posterior do giro temporal médio esquerdo. Menor vSC foi observado nas mesmas regiões, porém este achado não sobreviveu à correção para comparações múltiplas. Análise individual do [18F]FDG-PET cerebral revelou sete JFAs com claro hipometabolismo nas faces medial e lateral dos lobos temporais, nos lobos frontais e nas regiões temporoparietais. Os JFAs apresentaram ainda maior prevalência de anormalidades do septo pelúcido. Conclusão Os JFAs apresentam MCCr e vSC reduzidos nos lobos temporais, além de anormalidades do septo pelúcido, achados possivelmente relacionados a impactos cranianos repetitivos.

Examining differences in brain metabolism associated with childhood maltreatment and suicidal attempts in euthymic patients with bipolar disorder: a PET and machine learning study

Objective: Childhood maltreatment (CM) is a significant risk factor for the development and severity of bipolar disorder (BD) with increased risk of suicide attempts (SA). This study evaluated whether a machine learning algorithm could be trained to predict if a patient with BD has a history of CM or previous SA based on brain metabolism measured by positron emission tomography. Methods: Thirty-six euthymic patients diagnosed with BD type I, with and without a history of CM were assessed using the Childhood Trauma Questionnaire. Suicide attempts were assessed through the Mini International Neuropsychiatric Interview (MINI-Plus) and a semi-structured interview. Resting-state positron emission tomography with 18F-fluorodeoxyglucose was conducted, electing only grey matter voxels through the Statistical Parametric Mapping toolbox. Imaging analysis was performed using a supervised machine learning approach following Gaussian Process Classification. Results: Patients were divided into 18 participants with a history of CM and 18 participants without it, along with 18 individuals with previous SA and 18 individuals without such history. The predictions for CM and SA were not significant (accuracy = 41.67%; p = 0.879). Conclusion: Further investigation is needed to improve the accuracy of machine learning, as its predictive qualities could potentially be highly useful in determining histories and possible outcomes of high-risk psychiatric patients.

18F-FDG PET/CT Metabolic Parameters and Circulating Tumour DNA Mutation Abundance in Diffuse Large B-Cell Lymphoma: Correlation and Survival Analysis / 中国实验血液学杂志

OBJECTIVE@#To investigate the correlation between 18Fluoro-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) metabolic parameters and peripheral blood circulating tumour DNA (ctDNA) in patients with diffuse large B-cell lymphoma (DLBCL), and the prognostic value of these two types of parameters in predicting progression-free survival (PFS).@*METHODS@#Clinical, PET/CT and ctDNA data of DLBCL patients who underwent peripheral blood ctDNA testing and corresponding PET/CT scans during the same period were retrospectively analyzed. At the time of ctDNA sampling and PET scan, patients were divided into baseline and relapsed/refractory (R/R) groups according to different disease conditions. CtDNA mutation abundance was expressed as variant allele frequency (VAF), including maximum VAF (maxVAF) and mean VAF (meanVAF). Total metabolic tumour volume (TMTV) and total lesion glycolysis (TLG) were obtained by the 41% maximum normalized uptake value method, and the distance between the two farthest lesions (Dmax) was used to assess the correlation between PET parameters and ctDNA mutation abundance using Spearman correlation analysis. The receiver operating characteristic (ROC) curves were used to obtain the optical cut-off values of those parameters in predicting PFS in the baseline and R/R groups, respectively. Survival curves were outlined using the Kaplan-Meier method and log-rank test was performed to compare survival differences.@*RESULTS@#A total of 67 DLBCL patients ［28 males and 39 females, median age 56.0(46.0, 67.0) years］ were included and divided into baseline group (29 cases) and R/R group (38 cases). Among these PET parameters, baseline TMTV, TLG, and Dmax were significantly correlated with baseline ctDNA mutation abundance, except for maximum standardized uptake value (SUVmax) (maxVAF vs TMTV: r=0.711; maxVAF vs TLG: r=0.709; maxVAF vs Dmax: r=0.672; meanVAF vs TMTV: r=0.682; meanVAF vs TLG: r=0.677; meanVAF vs Dmax: r=0.646). While in all patients, these correlations became weaker significantly. Among R/R patients, only TMTV had a weak correlation with meanVAF (r=0.376). ROC analysis showed that, the specificity of TMTV, TLG and Dmax in predicting PFS was better than mutation abundance, while the sensitivity of ctDNA mutation abundance was better. Except R/R patients, TMTV, TLG, Dmax, and VAF were significantly different at normal/elevated lactate dehydrogenase in baseline group and all patients (all P<0.05). Survival curves indicated that high TMTV (>109.5 cm3), high TLG (>2 141.3), high Dmax (>33.1 cm) and high VAF (maxVAF>7.74%, meanVAF>4.39%) were risk factors for poor PFS in baseline patients, while only high VAF in R/R patients (both maxVAF and meanVAF >0.61%) was a risk factor for PFS.@*CONCLUSION@#PET-derived parameters correlate well with ctDNA mutation abundance, especially in baseline patients. VAF of ctDNA predicts PFS more sensitively than PET metabolic parameters, while PET metabolic tumour burden with better specificity. TMTV, TLG and VAF all have good prognostic value for PFS. PET/CT combined with ctDNA has potential for further studies in prognostic assessment and personalized treatment.

Biograph Vision 600 PET performance testing and analysis / 中国辐射卫生

Objective To test and analyze the performance of Biograph Vision 600 PET/CT according to the NEMA NU2—2012 standard to achieve reliable, repeatable, and inter-system comparable performance measurement, and to provide a basis for future equipment stability testing and status detection. Methods The Biograph Vision PET equipment features a detector based on silicon photomultipliers, with 3.2 mm lutetium oxyorthosilicate crystals and full cover of the scintillation region. The spatial resolution, sensitivity, noise-equivalent count rate, scatter fraction, coincidence count rate, image quality, scatter correction, and time-of-flight resolution of Biograph Vision PET were tested by referring to the test model and method of the NEMA NU2—2012 standard. Results The Biograph Vision 600 PET equipment showed lateral and axial spatial resolutions of 3.69 mm and 3.81 mm at 1 cm off-center of the field of view, respectively and of 4.29 mm and 4.48 mm at 10 cm, respectively. The sensitivity was 17.5 kcps/MBq. The time-of-flight resolution changed from 210 ps to 215 ps as the count rate increased to the peak noise equivalent count rate. The NEMA peak noise-equivalent count rate was 247 kcps at 30.3 kBq/ml. The corresponding scatter fraction was 34.8%. With the NEMA module, the overall image quality contrast range was 73.6%-92.8%, and the background variability was 2.3%-6.5%; the mean lung residual error was 3.4%; and the time-of-flight resolution was 210 ps. Conclusion This performance test was performed according to the NEMA NU2—2012 standard, showing that all parameters were better than the ex-factory standard, which can provide a reference for other institutions selecting equipment and also provide a basis for future equipment stability testing and status detection.

How much exposure dose does a patient receive in PET/CT examination? / 中国辐射卫生

@#Positron emission tomography/computed tomography (PET/CT) scanner is an irreplaceable instrument in clinical diagnosis. The exposure dose that a patient receives is the sum of the doses caused by PET and CT examination. This study discussed the exposure dose level that a patient received during PET/CT examination according to the research data. Like other radiological diagnostic methods, PET/CT examination brings benefits outweighing its radiation risk. It is not advisable to exaggerate or ignore the exposure dose. The patient’s exposure dose caused by PET/CT examination should be controlled as much as possible under the premise of meeting clinical needs.

Progress in application of positron emission tomography/computed tomography (PET/CT) imaging in tumor screening / 中国辐射卫生

@#Worldwide, the incidence of cancer is greatest in China. Tumor screening is effective to achieve early diagnosis, improve prognosis, increase the quality of life, and reduce mortality among cancer patients. Positron emission tomography/computed tomography (PET/CT) imaging provides metabolic data to support initial staging, treatment planning, and response evaluation in tumor screening, as well as tumor follow-up. The progressive integration of PET/CT imaging in radiotherapy has its basic principle in the biological heterogeneity of inter- and intra-tumor malignant lesions, and the radiation dose is required to be adjusted to achieve effective local tumor control among cancer patients. In addition, PET/CT imaging provides data on the biological features of tumor lesions, such as metabolism, hypoxia, and proliferation, which is useful to identify radiation-resistant regions and optimize treatment plans. These data are effective to reduce the uncertainty and variability in the anatomic description of tumor sites. This review summarizes the application of PET/CT imaging in common tumors.

Diagnostic Efficacy of 18F-FDG PET/CT in Detecting Bone Marrow Infiltration in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma / 生物医学与环境科学（英文）

OBJECTIVE@#Diffuse large B-cell lymphoma (DLBCL) is often associated with bone marrow infiltration, and 2-deoxy-2-(18F) fluorodeoxyglucose positron emission tomography/computed tomography ( 18F-FDG PET/CT) has potential diagnostic significance for bone marrow infiltration in DLBCL.@*METHODS@#A total of 102 patients diagnosed with DLBCL between September 2019 and August 2022 were included. Bone marrow biopsy and 18F-FDG PET/CT examinations were performed at the time of initial diagnosis. Kappa tests were used to evaluate the agreement of 18F-FDG PET/CT with the gold standard, and the imaging features of DLBCL bone marrow infiltration on PET/CT were described.@*RESULTS@#The total detection rate of bone marrow infiltration was not significantly different between PET/CT and primary bone marrow biopsy ( P = 0.302) or between the two bone marrow biopsies ( P = 0.826). The sensitivity, specificity, and Youden index of PET/CT for the diagnosis of DLBCL bone marrow infiltration were 0.923 (95% CI, 0.759-0.979), 0.934 (95% CI, 0.855-0.972), and 0.857, respectively.@*CONCLUSION@#18F-FDG PET/CT has a comparable efficiency in the diagnosis of DLBCL bone marrow infiltration. PET/CT-guided bone marrow biopsy can reduce the misdiagnosis of DLBCL bone marrow infiltration.

Research progress of FAPI PET/CT in the diagnosis of malignant liver tumors / 中华肝脏病杂志

Malignant liver tumors have a high incidence and mortality rate. Therefore, it is of great significance to promptly learn about tumor advancement status through relevant examinations for patients' follow-up, diagnosis, and therapy as well as the improvement of the five-year survival rate. The primary lesions and intrahepatic metastases of malignant liver tumors have been better demonstrated in the clinical study with the use of various isotope-labeled fibroblast activating protein inhibitors because of their low uptake in liver tissues and high tumor/background ratio, which provides a new method for early diagnosis, precise staging, and radionuclide therapy. In light of this context, a review of the research progress of fibroblast-activating protein inhibitors for the diagnosis of liver malignant tumors is presented.

Perianal Paget 's disease complicated with lung adenocarcinoma and anal canal carcinoma: A case report and literature review / 中南大学学报(医学版)

Perianal Paget's disease (PPD) is a rare malignant cutaneous tumor. This paper reported a case of PPD complicated by lung adenocarcinoma and anal canal cancer. The patient, a 76-year-old female, had been experiencing recurrent lower abdominal pain and perianal pruritus for the past 5 years. Upon physical examination, a cauliflower-like neoplasm in size of 5 cm×6 cm was observed on the right perianal skin, with local skin ulceration and a small amount of fluid discharge. The left perianal skin was also involved. In thoracoknee position, a hard mass was palpable in the rectal submucosa at 5-6 points 2 cm from the anal verge. Chest CT revealed multiple lesions in both lungs, indication of metastatic tumors. Further evaluation with fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) indicated multiple hypermetabolic nodules in the lungs, hypermetabolic lymph nodes throughout the body, early FDG uptake in a small patch of skin on the left hip, and increased FDG uptake in the anorectal region. Histopathological examination confirmed the diagnosis of lung adenocarcinoma. This resulted in the patient being diagnosed with PPD, lung adenocarcinoma, anal canal cancer, and systemic multiple lymph node metastasis. The combination of PPD with gastrointestinal tumors and other metachronous malignant tumors is highly prevalent. Colonoscopy, FDG-PET/CT, histopathology, and immunohistochemistry play crucial roles in early identification of local lymph node and distant involvement, facilitating the evaluation of potential malignant tumors and differential diagnosis. Treating methods for PPD are currently diverse, including postoperative combined or single chemotherapy, radiotherapy, targeted therapy, and photodynamic therapy. As trerapeutical options continue to develop, the extent and efficacy of surgery need to be reassessed.

Advances in molecular imaging of cerebral amyloid angiopathy / 中华神经科杂志

Cerebral amyloid angiopathy (CAA) is a common age-related small vessel disease characterized by amyloid-β (Aβ) deposition in the wall of small arterioles and capillaries of the leptomeninges and cerebral cortex. Several molecular imaging technologies such as amyloid-β positron-emission tomography (PET) and 18F-fluorodeoxyglucose-PET have been successfully applied in the patients with CAA. Amyloid-PET may indicate the distribution and burden of Aβ deposition by the tracer′s specific binding to the pathological markers, providing qualitative and quantitative information for the diagnosis of CAA. However, amyloid-β PET is inadequate to differentiate CAA from other Aβ-related diseases like Alzheimer′s disease. Other novel techniques of molecular imaging including tau-PET, single photon emission computed tomography and other highly selective PET radioligands have been investigated widely at present. This article mainly reviewed the advances in molecular imaging of CAA.

Clinical characteristics and analysis of diagnosis and treatment of 16 patients with GATOR1 complex-related epilepsy / 中华神经科杂志

Objective:To analyze the clinical manifestations, gene mutation characteristics and treatment effects of patients with GATOR1 complex-related epilepsy, and to explore the diagnosis and treatment of this disease.Methods:The medical history, electroencephalogram, brain imaging, genetic test results, treatment and follow-up data of patients with GATOR1 complex-related epilepsy who attended the Children′s Hospital Affiliated to Capital Institute of Pediatrics, Beijing Tsinghua Changgung Hospital, and Shanghai Deji Hospital from May 2017 to July 2022 were retrospectively analyzed.Results:A total of 16 patients with GATOR1 complex-related epilepsy were collected, including 7 males and 9 females. The age of onset of epilepsy was from 2 months to 14 years. Ten cases had focal seizures only, 2 cases had generalized seizures only, and 4 cases had coexistence of focal seizures and generalized seizures, of which generalized seizures included generalized tonic-clonic seizure, spastic seizure, and myoclonic seizure. Among the 16 patients, 2 had infantile spasms, 3 had familial focal epilepsy with variable focus, and 1 had sleep related hyperkinetic epilepsy. Electroencephalogram intervals suggested multiple brain areas discharge or diffuse discharge. A total of 13 DEPDC5 gene mutation sites, 1 NPRL2 gene mutation site, and 2 NPRL3 gene mutation sites were found; 4 sites of DEPDC5 gene were reported sites, the rest were unreported; all mutations had pathogenic significance; 8 cases had nonsense mutation, 1 case had large fragment deletion, 4 cases had frameshift mutation, 1 case had integer mutation, 2 cases had splicing mutation; 13 cases′ mutation was inherited from parents, 2 cases had new mutation, and 1 case had unverified mutation. Magnetic resonance imaging (MRI) showed 5 of the 16 patients were normal, and 11 had abnormal cerebral cortex structure, manifested as bottom-of-sulcus focal cortical dysplasia (FCD), abnormal formation of sulci and (or) gyri with or without ill-defined gray-white matter and malformation of cortical dysplasia of the bilateral brain. Seven patients underwent stereotactic electroencephalogram (SEEG) monitoring, and the SEEG showed low-amplitude fast rhythm at the beginning in 6 patients, of whom 5 cases started from the frontal lobe, and 1 case started from the parietal lobe. Eight patients were only treated with drugs, 1 with single-drug therapy and the rest with multi-drug combination therapy. Eight patients underwent surgery. Among them, 5 patients with DEPDC5 gene mutation underwent epileptogenic cortex excising after SEEG monitoring, and postoperative pathological examinations showed FCDⅡ, FCDⅢ or non-specific changes; 1 patient was waiting for surgery. One patient with NPRL3 gene mutation underwent epileptogenic foci resection and postoperative pathological examinations showed FCDⅡa; the other patient with NPRL3 gene mutation underwent radiofrequency thermocoagulation after SEEG monitoring. Follow-up showed that 3 patients were seizure-free with drug treatment, and 4 patients had fewer seizures after drug treatment. Six cases underwent epileptic foci resection. Five of them were assisted by SEEG to locate the epileptic foci before surgery and were seizure-free after the operation, but the range of surgical resection was wider than the abnormal range shown by MRI; whereas 1 case who was not assisted by SEEG showed no improvement. There was still 1 case who underwent SEEG-guided radiofrequency thermocoagulation and had no improvement after operation. Conclusions:GATOR1 complex-related epilepsy mostly manifests as focal seizures. SEEG shows that seizures originate from the frontal lobe more often, and cortical developmental abnormalities are often found. DEPDC5 gene mutations are the most common ones, mostly inherited from parents, with high incomplete penetrance rate. Therefore, genetic testing is recommended for non-acquired brain structural abnormalities. For those who are refractory to drugs, a radical cure can be obtained by resection of the epileptogenic foci after preoperative evaluation.

Automatic radiolabeling of the norepinephrine transporter targeted tracer 18F-mFBG and evaluation of 18F-mFBG PET/CT imaging in pheochromocytoma / 中华核医学与分子影像杂志

Objective:To fulfill the automatic radiolabeling of the norepinephrine transporter (NET) trancer 18F-meta-fluorobenzylguanidine (mFBG), and explore the 18F-mFBG PET/CT imaging effect of pheochromocytoma. Methods:On the basis of the chemical structure of mFBG, a spirocyclic iodonium ylide was used as the precursor to undergo a 3-step reaction sequence (radiofluorination, deprotection and neutralization) on AllinOne synthesis module. Purification by high performance liquid chromatography and formulation were conducted to generate 18F-mFBG. The corresponding quality control tests of 18F-mFBG product was performed. Afterwards, a postoperative patient with pheochromocytoma underwent 18F-mFBG PET/CT imaging. Results:The radiosynthesis was accomplished within 70 min, and 18F-mFBG was obtained in (17.8±2.4)% non-decay-corrected radiochemical yield ( n=5), with radiochemical purity >97% and molar activity >59.2 GBq/μmol. Sterility test, bacterial endotoxins test, abnormal toxicity test and the acetonitrile residue all met the requirements of Pharmacopoeia of the People′ s Republic of China (2020 Volume Ⅳ). The 18F-mFBG PET/CT imaging disclosed high uptake in pheochromocytoma and clear localization of lesions. Conclusions:The automatic radiolabeling of the NET targeted tracer 18F-mFBG is successfully realized by commercially available synthesis module, and the production quality meets all requirements for clinical translation. 18F-mFBG has a potential to image neuroendocrine lesions in clinical setting.

Dual-phase 18F-fluorocholine PET/CT imaging in uremic hyperparathyroidism / 中华核医学与分子影像杂志

Objective:To investigate the application value of dual-phase 18F-fluorocholine (FCH) PET/CT imaging in uremic hyperparathyroidism (uHPT). Methods:Twenty patients (10 males, 10 females, age: (46.8±12.3) years) who were diagnosed with uHPT and underwent neck ultrasound and dual-phase (5, 45 min) 18F-FCH PET/CT imaging at Affiliated Hospital of Southwest Medical University between December 2019 and March 2022 were retrospectively analyzed. Patients underwent parathyroidectomy within 1 month after PET/CT imaging. The sensitivity of neck ultrasound and dual-phase 18F-FCH PET/CT imaging for the diagnosis of hyperfunctioning parathyroid glands were compared based on the surgical results. The early- and late-phase 18F-FCH PET/CT images were compared visually and quantitatively, and the difference of SUV max between parathyroid hyperplasia and parathyroid adenoma was compared. The correlations between SUV max and important laboratory parameters and the volume of lesions measured on CT were tested. Fisher exact test, paired t test, independent-sample t test and Spearman rank correlation analysis were used for statistical analysis. Results:A total of 69 masses were removed in 20 patients with uHPT, and 55 parathyroid hyperplasia and 10 parathyroid adenomas were identified by pathology. Dual-phase 18F-FCH PET/CT imaging (87.69%, 57/65) was more sensitive than neck ultrasound (56.92%, 37/65) for the diagnosis of hyperfunction of the parathyroid gland ( P=0.001). The early imaging detected more lesions than late imaging (57 vs 49) respectively, which showing higher sensitivity (87.69%(57/65) vs 75.38%(49/65); P<0.001). The SUV max(5.75±2.21 vs 4.08±1.51) and the corresponding parathyroid-to-thyroid ratio (2.99±0.99 vs 3.57±1.30) were both significantly different between early and late imaging ( t values: 8.28, 4.33, both P<0.001). There were no significant differences between parathyroid hyperplasia and parathyroid adenoma in SUV max(early imaging: 5.08±2.27 vs 6.58±2.24; t=-1.90, P=0.063; late imaging: 3.89±1.54 vs 4.93±1.04; t=-1.94, P=0.059). The sum of SUV max of all lesions in early imaging was not correlated with preoperative serum parathyroid hormone (PTH) or Ca or P or lesion size ( rs values: from -0.22 to 0.06, all P>0.05). Conclusions:Dual-phase 18F-FCH PET/CT imaging has high sensitivity in the diagnosis of uHPT, and early and late imaging shows advantages in different aspects, with good preoperative localization ability. Therefore, for patients with uHPT, it is recommended to complete the dual-phase 18F-FCH PET/CT examination before surgery.

Diagnostic value of 18F-PSMA-1007 PET/CT in seminal vesicle invasion of prostate cancer / 中华核医学与分子影像杂志

Objective:To evaluate the diagnostic value of the 18F-prostate specific membrane antigen (PSMA)-1007 PET/CT in seminal vesicle invasion (SVI) of prostate cancer. Methods:Clinical and pathological materials of 88 patients (age: 51-84 years) who underwent radical prostatectomy (RP) between May 2019 and December 2021 in the First Affiliated Hospital of Xi′an Jiaotong University were analyzed retrospectively. All patients underwent 18F-PSMA-1007 PET/CT examination for primary staging before surgery. The diagnostic efficiency of 18F-PSMA-1007 PET/CT in SVI was obtained using postoperative pathological results as the " gold standard" and ROC curve was drawn. Furthermore, univariate and multivariate logistic regression analyses were used to screen the influencing factors for 18F-PSMA-1007 PET/CT prediction of SVI. Results:The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of 18F-PSMA-1007 PET/CT in diagnosing SVI were 79.55%(70/88), 72.73%(16/22), 81.82%(54/66), 57.14%(16/28) and 90.00%(54/60), respectively. The ROC AUC was 0.77. Results of univariate logistic regression showed that total prostate specific antigen (tPSA), primary SUV max, Gleason score, International Society of Urological Pathology (ISUP) grade group were associated with 18F-PSMA-1007 PET/CT prediction of SVI. Results of multivariate logistic regression showed that Gleason score (odds ratio ( OR)=2.04, 95% CI: 1.19-3.50, P=0.009) was a predictor of SVI in prostate cancer. Conclusion:18F-PSMA-1007 PET/CT has certain diagnostic value in SVI of prostate cancer, and combining with Gleason score can improve the diagnostic efficiency.

Predictive value of pre-surgical 18F-FDG PET/CT metabolic parameters for mediastinal lymph node metastasis in patients with lung adenocarcinoma / 中华核医学与分子影像杂志

Objective:To investigate predictive value of model based on pre-surgical 18F-FDG PET/CT metabolic parameters for mediastinal lymph node metastasis (LNM) in lung adenocarcinoma. Methods:A total of 288 patients with lung adenocarcinoma (135 males, 153 females, age (61.6±8.5) years) who diagnosed and treated in the Fourth Hospital of Hebei Medical University from January 2016 to February 2021 were enrolled retrospectively. All patients underwent 18F-FDG PET/CT examination within 1 month before operation, and underwent complete resection of primary lung tumor and standard lymph node dissection. PET/CT parameters were extracted (PET metabolic parameters: minimum SUV(SUV min), SUV max, SUV mean, SUV standard deviation (SUV std), metabolic tumor volume (MTV) and total lesion glycolysis (TLG); CT parameters: minimum CT value (HU min), maximum CT value (HU max), mean CT value (HU mean), CT value standard deviation (HU std)). Multivariate logistic regression analysis was used for screening parameters and establishing model to predict LNM. ROC curves analyses were used to evaluate the predictive performance of models. Results:Among 288 patients, 90 had LNM, and 361 metastatic lymph nodes (N1: 186, N2: 175) were reported by pathology. SUV min (odds ratio ( OR)=1.859, 95% CI: 1.074-3.220, P=0.027), SUV max ( OR=2.255, 95% CI: 1.306-3.893, P=0.004), SUV mean ( OR=0.277, 95% CI: 0.115-0.665, P=0.004) were predictors of LNM. The AUC of PET/CT model was 0.849 (95% CI: 0.804-0.893), and the sensitivity, specificity, accuracy, and positive and negative predictive values were 87.8%(79/90), 72.2%(143/198), 77.1%(222/288), 59.0%(79/134) and 92.9%(143/154), respectively. Conclusion:The model based on 18F-FDG PET/CT metabolic parameters can improve the accuracy of pre-surgical N-staging in patients with lung adenocarcinoma.