Correlation of brain cell glucose metabolism and patient's condition in children with epileptic encephalopathy An assessment using fluorine-18-fluoro-2-deoxy-D-glucose positron emission computed tomography

We examined a total of 16 children with epileptic encephalopathy using fluorine-18-fluoro-2-deoxy-D-glucose （18F-FDG） positron emission computed tomography （PET）, magnetic resonance imaging （MRI） and electroencephalography. Children with infantile spasms showed significant mental retardation, severely abnormal electroencephalogram recordings, and bilateral diffuse cerebral cortex hypometabolism with I^F-FDG PET imaging. MRI in these cases showed brain atrophy, multi-micropolygyria, macrogyria, and porencephalia. In cases with Lennox-Gastaut syndrome, 18F-FDG PET showed bilateral diffuse glucose hypometabolism, while MRI showed cortical atrophy, heterotopic gray matter and tuberous sclerosis. MRI in cases with myoclonic encephalopathy demonstrated bilateral frontal and temporal cortical and white matter atrophy and 18F-FDG PET imaging showed bilateral frontal lobe atrophy with reduced bilateral frontal cortex, occipital cortex, temporal cortex and cerebellar glucose uptake. In children who could not be clearly classified, MRI demonstrated cerebral cortical atrophy and ~aF-FDG PET exhibited multifocal glucose hypometabolism. Overall, this study demonstrated that the degree of brain metabolic abnormality was consistent with clinical seizure severity. In addition, ~SF-FDG PET imaging after treatment was consistent with clinical outcomes. These findings indicate that ~SF-FDG PET can be used to assess the severity of brain injury and prognosis in children with epileptic encephalopathy.

Congenital hyperinsulinism:Role of fluorine-18L-3, 4 hydroxyphenylalanine positron emission tomography scanning

Congenital hyperinsulinism(CHI) is a rare but complex heterogeneous disorder caused by unregulated secre-tion of insulin from the β-cells of the pancreas leading to severe hypoglycaemia and neuroglycopaenia. Swift diagnosis and institution of appropriate management is crucial to prevent or minimise adverse neurodevel-opmental outcome in children with CHI. Histologically there are two major subtypes of CHI, diffuse and focal disease and the management approach will significantly differ depending on the type of the lesion. Patients with medically unresponsive diffuse disease require a near total pancreatectomy, which then leads on to the de-velopment of iatrogenic diabetes mellitus and pancre-atic exocrine insufficiency. However patients with focaldisease only require a limited pancreatectomy to re-move only the focal lesion thus providing complete cure to the patient. Hence the preoperative differentiation of the histological subtypes of CHI becomes paramount in the management of CHI. Fluorine-18L-3, 4-hydroxy-phenylalanine positron emission tomography(18F-DOPA-PET) is now the gold standard for pre-operative differentiation of focal from diffuse disease and locali-sation of the focal lesion. The aim of this review article is to give a clinical overview of CHI, then review the role of dopamine in β-cell physiology and finally discuss the role of 18F-DOPA-PET imaging in the management of CHI.

Cost-effectiveness of Fluorine-18-Fluorodeoxyglucose positron emission tomography in tumours other than lung cancer: A systematic review

AIM: To systematically review published data on the cost-effectiveness of Fluorine-18-Fluorodeoxyglucose positron emission tomography(FDG-PET) or PET/computed tomography(PET/CT) in tumours other than lung cancer. METHODS: A comprehensive literature search of studies published in PubMed/MEDLINE, Scopus and Embase databases through the 10th of October in 2013 was carried out. A search algorithm based on a combination of the terms:(1) "PET" or " PET/computed tomography(PET/CT)" or "positron emission tomography"; and(2) "cost-effectiveness" or "cost-utility" or "cost-efficacy" or "technology assessment" or "health technology assessment" was used. Only cost-effectiveness or cost-utility analyses in English language were included. Exclusion criteria were:(1) articles not within the field of interest of this review;(2) review articles, editorials or letters, conference proceedings; and(3) outcome evaluation studies, cost studies or health technology assessment reports. For each included study, information was col-lected concerning basic study, type of tumours evaluated, perspective/type of study, results, unit and comparison alternatives. RESULTS: Sixteen studies were included. Head and neck tumours were evaluated in 4 articles, lymphoma in 4, colon-rectum tumours in 3 and breast tumours in 2. Only one article was retrieved for melanoma, oesophagus and ovary tumours. Cost-effectiveness results of FDG-PET or PET/CT ranged from dominated to dominant. CONCLUSION: Literature evidence about the costeffectiveness of FDG-PET or PET/CT in tumours other than lung cancer is still limited. Nevertheless, FDGPET or PET/CT seems to be cost-effective in selective indications in oncology(staging and restaging of head and neck tumours, staging and treatment evaluation in lymphoma).

Significance of incidental focal fluorine-18 fluorodeoxyglucose uptake in colon/rectum,thyroid,and prostate:With a brief literature review

BACKGROUND Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography(F-18 FDG PET/CT),a functional imaging method,is usually performed on the entire torso,and regions of unexpected suspicious focal hypermetabolism are not infrequently observed.Among the regions,colon,thyroid,and prostate were found to be the common organs in a recent umbrella review.Some studies reported that a high rate of malignancy was shown in incidentally identified focal hypermetabolic regions and suggested that further examinations should not be ignored.AIM To investigate the malignancy rate of incidental focal FDG uptake,useful PET parameters and their cutoffs in discrimination between malignant and benign lesions.METHODS Retrospectively,the final reports of 16510 F-18 FDG PET/CT scans performed at our hospital between January 2016 and March 2022 were reviewed to identify incidentally observed FDG uptake in the colon/rectum,thyroid,and prostate.The scans of patients with current or prior malignancies at each corresponding location,without the final reports of histopathology or colonoscopy(for colon and rectum)for the corresponding hypermetabolic regions,or with diffuse(not focal)hypermetabolism were excluded.Finally,88 regions of focal colorectal hypermetabolism in 85 patients(48 men and 37 women with mean age 67.0±13.4 years and 63.4±15.8 years,respectively),48 focal thyroid uptakes in 48 patients(12 men and 36 women with mean age 62.2±13.1 years and 60.8±12.4 years,respectively),and 39 focal prostate uptakes in 39 patients(mean age 71.8±7.5 years)were eligible for this study.For those unexpected focal hypermetabolic regions,rates of malignancy were calculated,PET parameters,such as standardized uptake value(SUV),capable of distinguishing between malignant and benign lesions were investigated,and the cutoffs of those PET parameters were determined by plotting receiver operating characteristic curves.RESULTS In the colon and rectum,29.5%(26/88)were malignant and 33.0%(29/88)were premalignant lesions.Both SUVmax and SUVpeak differentiated malignant/premalignant from benign lesions,however,no parameters could distinguish malignant from premalignant lesions.Higher area under the curve was shown with SUVmax(0.752,95%CI:0.649-0.856,P<0.001)and the cutoff was 7.6.In the thyroid,60.4%(29/48)were malignant.The majority were well-differentiated thyroid cancers(89.7%,26/29).The results of BRAF mutation tests were available for 20 of the 26 welldifferentiated thyroid cancers and all 20 had the mutation.Solely SUVmax differentiated malignant from benign lesions and the cutoff was 6.9.In the prostate,56.4%(22/39)were malignant.Only SUVmax differentiated malignant from benign lesions and the cutoff was 3.8.Overall,among the 175 focal hypermetabolic regions,60.6%(106/175)were proven to be malignant and premalignant(in colon and rectum)lesions.CONCLUSION Approximately 60%of the incidentally observed focal F-18 FDG uptake in the colon/rectum,thyroid,and prostate were found to be malignant.Of the several PET parameters,SUVmax was superior to others in distinguishing between malignant/premalignant and benign lesions.Based on these findings,incidental focal hypermetabolism should not be ignored and lead physicians to conduct further investigations with greater confidence.

Assessment of incidental focal colorectal uptake by analysis of fluorine-18 fluorodeoxyglucose positron emission tomography parameters

BACKGROUND Colon and rectal cancers are among the top five cancers worldwide in terms of their incidence and mortality rates.As the treatment options for cure include surgery even in specific advanced-stage cases,the early detection of lesions is important for applying active treatment methods.Fluorine-18 fluorodeoxyglucose(F-18 FDG)positron emission tomography/computed tomography(PET/CT)is an established imaging study for many types of cancers;however,physiologic uptake in the gastrointestinal tract is a frequent finding and may interfere with lesion identification.Nevertheless,as unexpectedly observed focal colorectal F-18 FDG uptake may harbor malignant lesions,further examination must not be avoided.AIM To assess the clinical implications of unexpected focal colorectal F-18 FDG uptake by analyzing FDG PET parameters.METHODS A total of 15143 F-18 FDG PET/CT scans performed at our hospital between January 2016 and September 2021 were retrospectively reviewed to identify incidentally observed focal colorectal FDG uptake.Finally,83 regions showing focal colorectal FDG uptake with final histopathological reports from 80 patients(45 men and 35 women with mean ages of 66.9±10.7 years and 63.7±15.3 years,respectively)were eligible for inclusion in the present study.Each focal hypermetabolic colorectal region was classified as malignant,premalignant,or benign according to the histopathological report.PET parameters such as maximum and peak standardized uptake value(SUVmax and SUVpeak),metabolic tumor volume(MTV),mean SUV of the metabolic tumor volume(mSUVmtv),and total lesion glycolysis(TLG)were measured or calculated for the corresponding hypermetabolic regions.Parametric and nonparametric statistical comparisons of these parameters were performed among the three groups.Receiver operating characteristic curves were plotted to identify cut-off values.RESULTS The detection rate of incidental focal colorectal uptake was 0.53%(80/15,143).Of the 83 regions with unexpected focal colorectal hypermetabolism,28.9%(24/83)were malignant,32.5%(27/83)were premalignant,and 38.6%(32/83)were benign.Overall,61.4% of the regions had malignant or premalignant lesions.SUVmax,SUVpeak,and mSUVmtv differentiated malignant and/or premalignant lesions from benign lesions with statistical significance(P<0.05).mSUVmtv3.5 differentiated malignant from benign lesions,with the largest area under the curve(AUC)of 0.792 and a cut-off of 4.9.SUVmax showed the largest AUC of 0.758 with a cut-off value of 7.5 for distinguishing between premalignant and benign lesions.Overall,SUVmax with a cut-off value of 7.6(AUC:0.770,95% confidence interval(CI):0.668-0.872;sensitivity,0.686;specificity,0.688)was a superior parameter for distinguishing between malignant/premalignant and benign lesions or physiologic uptake.No parameters differentiated malignant from premalignant lesions.Moderate or weak positive correlations were observed between the long diameter of the malignant lesions and PET parameters such as SUVpeak and some mSUVmtv.CONCLUSION Approximately two-thirds(61.4%)of incidental focal hypermetabolic colorectal regions were malignant/premalignant lesions,for which SUVmax was an independent diagnostic parameter.Unexpected suspicious focal colorectal FDG uptake should not be avoided and consideration for further evaluation is strongly recommended not to miss the two-thirds.

Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography for Osteochondromas Utilizing a Triple-Time Point Protocol

Purpose: The purpose of this study was to assess solitary osteochondroma and hereditary multiple osteochondral exostoses (HMOCE) utilizing FDG PET and a triple time point protocol. Methods: Seven patients were consented and recruited for PET evaluation of presumed benign osteochondroma. Following injection of 15 mCi of FDG, the lesion(s) of interest was imaged with PET-CT at 45 minutes post injection, whole body at 50 minutes post, and lesion of interest at 95 minutes post injection. A maximum standardized uptake value (SUVmax) was obtained for the lesion(s) of interest at each time point, and an SUVΔ was calculated for each lesion of interest from the first time point to the third time point. Results: 16 lesions from 7 patients were included in the study. Mean SUVmax for all 3 time points was 1.04 with a standard deviation of 0.50 (range 0.3 - 2.2). The mean SUV was 0.096 with a range of 0 - 0.4. Among the 3 patients with histologically confirmed osteochondromas, mean SUVmax was 0.67, with standard deviation of 0.23 and range of 0.3 to 1.0. The mean SUVΔ13 was 0.081 (range 0 - 0.4), mean SUVΔ12 was 0.10 (0 - 0.3), and mean SUVΔ23 was 0.11 (range 0 - 0.4) (p = 0.74). Conclusion: Benign lesions were found to not have progressively increasing uptake on multiple time point FDG PET. Until chondrosarcomas are evaluated using triple time point 18FDG PET, its applicability in the evaluation of osteochondroma versus malignant change remains uncertain.

Fluorine-18 Radiochemistry: A Novel Thiol-Reactive Prosthetic Group, [18F]FBAMPy

A novel thiol-reactive bifunctional agent, an analogue of fluorobenzaldehyde-O-[6-(2,5-dioxo-2,5- dihydro-pyrrol-1-yl)-hexyl]oxime, (FBAM) has been synthesized. The new prosthetic group, [18F]- FBAMPy, replaces the 4-fluorophenyl moiety with a 2-fluoropyridinyl moiety leading to increased polarity (FBAM analytical HPLC Rf = 6.4 min;FBAMPy Rf = 4.8 min) while retaining the sulfur-reactive pendant. By altering the polarity of the molecule, this new prosthetic group should have significant impact in coupling it with small peptides and other biomolecules.

^(18)F-FDG的放射性标记、显像原理与临床研究进展

PET/CT是当今最先进的诊断技术之一,实现了解剖学影像与功能学影像的融合。18 F-FDG是最为重要的正电子药物,其使用量占全部PET/CT显像的95%以上。FDG-PET已经广泛应用于诊断肿瘤、心脏病和癫痫等多种疾病。本文回顾了18F-FDG的发展历史,介绍了18 F-FDG的制备与质量控制,分析了18 F-FDG显像原理,阐述了FDG-PET等临床应用研究进展。

Potential of (18)~F-FDG-PET as a valuable adjunct to clinical and response assessment in rheumatoid arthritis and seronegative spondyloarthropathies

AIM: To evaluate the role of fluorine-18-labeled fluorodeoxyglucose positron emission tomography (18F-FDG PET) in various rheumatic diseases and its potential in the early assessment of treatment response in a limited number of patients. METHODS: This study involved 28 newly diagnosed patients, of these 17 had rheumatoid arthritis (RA) and 11 had seronegative spondyloarthropathy (SSA). In the SSA group, 7 patients had ankylosing spondylitis, 3 had psoriatic arthritis, and one had non-specific SSA. Patients with RA were selected as per the American College of Rheumatology criteria. One hour after FDG injection, a whole body PET scan was performed from the skull vertex to below the knee joints using a GE Advance dedicated PET scanner. Separate scans were acquired for both upper and lower limbs. Post-treatment scans were performed in 9 patients in the RA group (at 6-9 wk from baseline) and in 1 patient with psoriatic arthropathy. The pattern of FDG uptake was analysed visually and quantified as maximum standardized uptake value (SUVmax) in a standard region of interest. Metabolic response on the scan was assessed qualitatively and quantitatively and was correlated with clinical assessment. RESULTS: The qualitative FDG uptake was in agreement with the clinically involved joints, erythrocyte sedimentation rate, C-reactive protein values and the clinical assessment by the rheumatologist. All 17 patients in the RA group showed the highest FDG avidity in painful/swollen/tender joints. The uptake pattern was homogeneous, intense and poly-articular in distribution. Hypermetabolism in the regional nodes (axillary nodes in the case of upper limb joint involvement and inguinal nodes in lower limb joints) was a constant feature in patients with RA. Multiple other extra-articular lesions were also observed including thyroid glands (in associated thyroiditis) and in the subcutaneous nodules. Treatment response was better appreciated using SUVmax values than visual interpretation, when compared with clinical evaluation. Four patients showed a favourable response, while 3 had stable disease and 2 showed disease progression. The resolution of regional nodal uptake (axillary or inguinal nodes based on site of joint involvement) in RA following disease modifying anti-rheumatoid drugs was noteworthy, which could be regarded as an additional parameter for identifying responding patients. In the SSA group, uptake in the affected joint was heterogeneous, low grade and nonsymmetrical. In particular, there was intense tendon and muscular uptake corresponding to symptomatic joints. The patients with psoriatic arthritis showed intense FDG uptake in the joints and soft tissue. CONCLUSION: 18F-FDG PET accurately delineates the ongoing inflammatory activity in various rheumatic diseases (both at articular and extra-articular sites) and relates well to clinical symptoms. Different metabolic patterns on FDG-PET scanning in RA and SSA can have important implications for their diagnosis and management in the future with the support of larger studies. FDG-PET molecular imaging is also a sensitive tool in the early assessment of treatment response, especially when using quantitative information. With these benefits, FDG-PET could play a pivotal clinical role in the management of inflammatory joint disorders in the future.

Clinical role of ^(18)F-FDG PET/CT-based simultaneous modulated accelerated radiotherapy treatment planning for locally advanced nasopharyngeal carcinoma

Objective The aim of this study was to compare the long-term local control, overall survival, and late toxicities of positron emission tomography/computed tomography （PET/CT）-guided dose escalation radio- therapy versus conventional radiotherapy in the concurrent chemoradiotherapy treatment of locally ad- vanced nasopharyngeal carcinoma （NPC）. Methods Atotal of 48 patients with stage IIl-IVa NPC were recruited and randomly administered PET/CT- guided dose escalation chemoradiotherapy （group A） or conventional chemoradiotherapy （group B）. The dose-escalation radiotherapy was performed using the simultaneous modulated accelerated radiotherapy technique at prescribed doses of 77 gray （Gy） in 32 fractions （f） to the gross target volume （GTV）： planning target volume （PTV） 1 received 64 Gy/32 f, while PTV2 received 54.4 Gy/32 f. Patients in group B received uniform-dose intensity-modulated radiotherapy, PTV1 received 70 Gy/35 f and PTV2 received 58 Gy/29 f. Concurrent chemotherapy consisted of cisplatin [20 mg/m2 intravenous （IV） on days 1-4] and docetaxel （75 mg/m2 IV on days 1 and 8） administered during treatment weeks 1 and 4. All patients received 2-4 cycles of adjuvant chemotherapy of the same dose and drug regimen. Results The use of fluorine-18-fluorodeoxyglucose （18F-FDG） PET/CT significantly reduced the treat- ment volume delineation of the GTV in 83.3% （20/24） of patients. The 5-year local recurrence-free survival rates of the two groups were 100% and 79.2%, respectively （P = 0.019）. The 5-year disease free survival （DFS） rates were 95.8% and 75.0%, respectively （P = 0.018）. The 5-year local progression-free survival and DFS rates were significantly different. The 5-year overall survival （OS） rates were 95.8% and 79.2%, re- spectively. Differences in OS improvement were insignificant （P = 0.079）. Late toxicities were similar in the two groups. The most common late toxicities of the two arms were grade 1-2 skin dystrophy, xerostomia, subcutaneous fibrosis, and hearing loss. There were no cases of grade 4 late toxicity. Conclusion The use of 18F-FDG PET/CT-guided dose escalation radiotherapy is well tolerated and can reduce local recurrence rates for patients with locally advanced NPC compared to conventional chemora- diotherapy.

抗癌中药活性成分毛兰素衍生物^(18)F-FEE的^(18)F标记及其体内性质MicroPET/CT评价

目的:开展抗癌中药活性成分毛兰素衍生物氟乙氧基毛兰素(fluoroethoxylerianin,FEE)的^(18)F标记及^(18)F-FEE的Micro正电子发射体层成像(positron emission tomography,PET)/计算机体层成像(computed tomography,CT),初步探索^(18)F等正电子核素标记与PET/CT在中药活性成分来源的新药评价中的应用。方法:开展^(18)F-FEE的制备条件优化实验,包括影响^(18)F标记和水解反应的多种反应条件,利用放射性薄层色谱法(radio-TLC)检测标记率和水解效率,放射性高效液相色谱法(radio-HPLC)测量^(18)F-FEE的放射化学纯度,并进行正常BALB/c小鼠与HepG2细胞的BALB/c裸小鼠移植瘤模型的体内生物分布和MicroPET/CT评价。结果:优化的^(18)F标记反应条件是时间10 min、温度100℃、前体浓度5 mg/mL、溶剂为乙腈,优化的水解反应条件是时间10 min、温度100℃、HCl溶液浓度6 mol/L。根据优化条件,成功合成了^(18)F-FEE,其放射化学纯度大于95%。正常小鼠生物分布和MicroPET/CT显示,^(18)F-FEE主要分布于肝、肠、肾和膀胱等代谢组织,心、肺等组织的分布较低。HepG2肝癌细胞移植瘤模型MicroPET/CT发现,^(18)F-FEE长时间弥散分布于肿瘤组织,肿瘤%ID/g高,注射60 min后肿瘤-肌肉比值(T/M)高达10以上。结论:本研究优化了抗癌中药活性成分毛兰素衍生物^(18)F-FEE的优化制备条件,^(18)F-FEE的合成条件可靠、放射化学纯度高,在体内主要分布于肝、肠、肾等代谢组织,而且其在HepG2肿瘤内分布明显,为FEE抗肿瘤作用提供了直观的实验手段,为抗癌天然活性中药成分及其衍生物提供了新的评价技术。

Improved preparation and chemical kinetics on fully automated synthesis of [^(18)F]-THK523,a PET imaging probe for Tau pathologies

Extensive accumulation of neurofibrillary tangles(NFTs)consistently correlate with the degree of cognitive impairment and neuronal circuitry deterioration associated with Alzheimer's disease.However,no PET probe is currently available for selective detection of NFTs in the living human brain.[^(18)F]-THK523 was developed as a potential in vivo imaging probe for tau pathology.In this paper,we report a new protected precursor,2-((2-(4-((tert-butoxycarbonyl)amino)phenyl)quinolin-6-yl)oxy)ethyl 4-methylbenzenesulfonate(THK-7),instead of2-((2-(4-aminophenyl)quinolin-6-yl)oxy)ethyl 4-methylbenzenesulfonate(BF241),and an improved automated radiosynfhesis of[^(18)F]-THK523 and the study on chemical kinetics of the labeling reaction of[^(18)F]-THK523,with high-yield(70±5%,n=6,decay-corrected to end of bombardment),and high radiochemical purity(>90%)and specific activity(2.5±0.5Ci/umol)from protected precursor on fully automated module at the end of radiosynthesis(45-55 min).The chemical kinetics for[^(18)F]-THK523 demonstrates that nucleophilic substitution can be carried out easily with protected precursor.

Radiosynthesis and biodistribution of [^(18)F]-tetracosactide using a semi-automated [^(18)F]SFB production module

In order to prepare a specific melanocortin type 2 receptor (MC2R) ligand, β1-24-corticotrophin was prepared in one-step reaction with [18F] SFB and β-1-24-corticotrophin pharmaceutical solution (1 mg/mL, pH=6.5). [18F]SFB was prepared in a semi-automated module in two steps with an overall radiochemical yield of 47% to EOB (not-decay corrected) in 90 min. The 18F-labeled intermediates and 18F-labeled peptide was checked by RTLC and HPLC. The results show that the radiochemical purity is >95% and the yield to EOB (not-decay corrected) is 29% for final 18F-labeled peptide at optimized conditions. Preliminary in vivo studies in normal mice were performed to determine biodistribution of the 18F-labeled peptide for 150 min. The results show that the major tracer uptake is consistent with the natural distribution of MC2R receptors in mammals. Testes/blood and testes/muscle ratios for 18F-labeled peptide at 150 min were 184 and 1.56, respectively, and adipocyte/blood and adipocyte/muscle ratios at 120 min were 221 and 142, respectively. The data support the specific receptor binding of the radiolabeled peptide as reported for MC2R receptor accumulation in adipocytes and testes and demonstrates the retention of biological activity of the peptide. This tracer can be used in detection of MC2R distribution in malignancies and sex organ diseases.

The possible value of ~18F-FDG positron emission tomography/computerized tomography imaging in detection of atherosclerotic plaque

Objective：To evaluate the clinical value with positron emission tomography/computerized tomography（PET/CT） imaging for the detection of vulnerable plaque in atherosclerotic lesions. Methods：Sixty people with a age of over 60[mean age （69.2 ± 7.1）years] underwent three dimension（3D） whole-body fluorine-18-2-fluoro-2-deoxy-D-glucose（^18F-FDG） PET/CT imaging and were evaluated retrospectively, including 6 cases assessed as normal and 54 cases with active atherosclerotic plaque. Fifty-four cases with SUVs and CT values in the aortic wall of high-FDG-uptake were measured retrospectively. These high-FDG-uptake cases in the aortic wall were divided into three groups according their CT value. Cases in group 1 had high uptake in atherosclerotic lesions of the aortic wall with CT value of less than 60 Hu（soft plaque）. Cases in group 2 had high uptake with CT value between 60-100 Hu （intermediate plaque）, Cases in group 3 had high uptake with CT value more than 100 Hu（calcified plaque）, Group 4 was normal. Results： In group 1, there were 42 high-FDG-uptake sites （average SUV 1.553 ± 0.486）. In group 2, there were 30 high-FDG-uptake sites（average SUV 1.393 ± 0.296）. In group 3, there were 36 high-FDG-uptake sites（average SUV 1.354 ± 0.189）. In group 4, there were 33 normal-FDG-uptake sites （average SUV was 1.102 ± 0.141）, The SUVs showed significant difference among the four groups（F = 678.909, P = 0.000）. There were also significant difference found between the normal-FDG-uptake group and the high-FDG-uptake groups（P = 0.000, 0.000, 0.001, respectively）. Conclusion：Different degrees of ^18F-FDG uptake in active large atherosclerotic plaque were shown in different stages of atherosclerotic plaque formation. The soft plaque had the highest FDG uptake in this study. This suggested that ^18F- FDG PET/CT imaging may be of great potential value in early diagnosis and monitoring of vulnerable soft plaque in atherosclerotic lesions.

The Role of ¹⁸F-FDG PET/CT in Staging Breast Carcinoma in Hanoi Oncology Hospital, Vietnam

Purpose: This study aimed to evaluate the role of 18F-FDG PET/CT scans in staging breast carcinoma. Materials and Methods: A descriptive study on 46 patients who were diagnosed with breast carcinoma in Hanoi Oncology Hospital, Vietnam from June 2019 to June 2021. Those patients underwent 18F-FDG PET/CT scans for pre-treatment staging. Results: There was a positive correlation between the size of primary tumors and their SUV (p < 0.0001, r = 0.759). The mean SUV was reported to be 2.5 for tumors under 2 cm, 5.89 for tumors from 2 - 5 cm, 13.6 for tumors above 5 cm, and 8.23 for skin invasive lesions. In terms of regional lymph node metastasis detection, the sensitivity and specificity of 18F-FDG PET/CT were 75% and 100%, respectively. The rate of distant metastasis detection was 15.2% (7/46 patients). Metastatic lesions were found in bone, lungs, liver, and lymph nodes. There was a significant difference in SUV among organs (p < 0.001), with the highest SUV found in bone metastasis. The rates of stage I, II, III and IV diagnosed after PET/CT are 8.7%;45.7%;30.4% and 15.2% respectively, compared to 10.9%;54.3%;32.6%;2.2% before taking 18F-FDG PET/CT. After PET/CT, 17.4% patients (8/46) had their treatment plan changed. Conclusions: 18F-FDG PET/CT plays an important role in staging breast carcinoma. Determining accurately the breast carcinoma stage by 18F-FDG PET/CT could help alter treatment strategy to best suit with patients, and avoid unnecessary surgery.

DNA三角双锥结构的放射性标记

分别采用点击化学方法对DNA三角双锥结构进行氟-18标记研究,采用二氯亚锡还原法对DNA三角双锥结构进行锝-99m标记研究.结果表明,点击化学方法不适用于DNA三角双锥结构的氟-18标记;而采用二氯亚锡还原法则制得了以DNA三角双锥结构为载体的分子影像探针99mTc-DBNs.

Imaging of atherosclerotic aorta of rabbit model by detection of plaque inflammation with fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography

Abstract：Background Atherosclerotic plaque rupture is the primary mechanism of thrombosis which plays a key role in the onset of acute coronary syndromes. Detection of these plaques prone to rupture （vulnerable plaque） could be clinically significant for prevention of cardiac events. It has been shown that high metabolism cells have a high uptake of fluorine-18 fluorodeoxyglucose （18F-FDG）. The objective of this study was to investigate the correlation of FDG uptake and the immuno-histochemistry parameters of plaques, and the effect of atorvastatin on vulnerable atherosclerotic plaque in a rabbit model.Methods Ten male New Zealand White rabbits were divided into three groups as follows： （1） normal control group （n=2,C group）： the animals were fed a standard diet at 120 g/d and were given water ad labium; （2） atherosclerosis group （n=4,As group）： animals were fed with high fat diet for 5 months after aortic endothelia damage; （3） treatment group （atherosclerosis ＋ atorvastatin, n=4, Statin group）： animals were fed with high fat diet for 5 months and then changed into normal chow plus atorvastatin （2.5 mg·d-1·kg-1） treatment for another 4 months. Then these four rabbits were imaged with fluorine-18 fluorodexyglucose positron emission tomography/computed tomography （PET/CT） and sacrificed for pathohistologic studies. FDG uptake by the aorta was expressed as target-to-background ratio （TBR）. Maximal standardized uptake value （SUV） was measured over the thoracic and abdominal aortas. The aortic smooth muscle cell （SMC） number, CD-14 antibody positive cell （macrophage） number and the ratio of the thickness of fibrous cap to the thickness of lipid core （cap-to-core ratio） in atherosclerotic plaques were analyzed.Results As group showed significantly higher uptake of FDG than C group （SUVs： 0.746±0.172 vs. 0.286±0.073, P 〈0.001）. After 4 months of atorvastatin treatment and the modification of diet, SUVs decreased significantly （Statin group：0.550±0.134, compared to As group, P 〈0.001）. However, no marked difference was found in TBR, the number of macrophages, the number of SMC and the cap-to-core ratio in the aortic segments between Statin group and As group.The correlation of aortic FDG uptake with SMC assessed by histopathology was negatively significant （r=0.57, P〈0.001）. When aortic FDG uptake was expressed as TBR, it correlated significantly （r=0.69, P 〈0.001） with the macrophage number, and also correlated significantly （r=0.78, P 〈0.001） with the cap-to-core ratio.Conclusion 18F-FDG PET/CT might serve as a useful non-invasive imaging technique for detection of atherosclerotic plaque and potentially permit monitoring of relative changes in inflammation within the atherosclerotic lesion.

一种肿瘤凋亡正电子发射断层显像探针的制备与表征

设计开发了一个靶向半胱氨酸天冬蛋白酶(caspase-3)的新型正电子发射断层显像(PET)探针[^(18)F]SF-DEVD-HE_(3),用于肿瘤细胞凋亡的可视化检测,对肿瘤疗效进行及时评价。该探针由四部分组成:caspase-3特异性识别的底物序列,Ac-Asp-Val-Glu-Asp(DEVD);分子内缩合基团,氰基苯并噻唑(CBT)和半胱氨酸(Cys);标记基团,三氟化硼(AmBF_(3))以及肽链,组氨酸-谷氨酸-组氨酸-谷氨酸-组氨酸-谷氨酸(HEHEHE)。采用化学合成和固相多肽合成法获得标记前体,利用^(18)F-^(19)F同位素交换法对其进行氟-18标记获得目标探针[18F]SF-DEVD-HE_(3)。测定了探针的脂水分配系数和稳定性等理化性质。结果显示,利用简化的合成方案以较高的产率(39.1%)获得标记前体;[18F]SF-DEVD-HE_(3)具有较高的放射标记产率(RLY,42.8%)和放射化学纯度(RCP,>99%);在磷酸缓冲溶液(PBS)和胎牛血清(FBS)中具有良好的稳定性;脂水分配系数(log P)为-1.28±0.05。结果表明,[18F]SF-DEVD-HE_(3)易于合成和放射性标记,具有良好的稳定性和水溶性,是一个潜在的检测肿瘤凋亡的PET探针。

一种caspase-3靶向激活型PET分子探针的制备与表征

诱导肿瘤细胞凋亡是多种肿瘤治疗方案的作用机制之一,因此检测肿瘤细胞是否产生凋亡已成为评价肿瘤治疗疗效的一种重要指标。以caspase-3为靶点设计凋亡靶向特异性探针,通过对其表达水平进行监测可以及时评估肿瘤疗效。本研究报道了一种靶向caspase-3的正电子发射断层显像(PET)探针[^(18)F]8。采用简便的固相合成法和点击缩合法合成多肽和前体8,利用^(18)F-^(19)F氟离子交换法进行放射性核素氟-18标记,得到放射化学产率16%和放射化学纯度95%的探针[^(18)F]8。探针[^(18)F]8在PBS和小鼠血清中具有较好的稳定性,脂水分配系数Log P为-1.69±0.01,表明探针亲水性较好。高效的合成方法以及良好的理化性质为探针应用于肿瘤凋亡模型的PET成像研究奠定了良好的基础。

Peptides Radiofluorination: Main Methods and Highlights

Peptides have an important role in organism and its high quantity present in tumors leading to development of radiolabeled peptides for tumor-specific imaging. Once the traditional methodologies used for radiofluorination do not work with peptides, due to their harsh conditions, other radiolabeling strategies had to be developed to supply the need. Direct radiofluorination is either an inefficient method, and the use of bidirectional groups, or prosthetic groups, is needed to enable the binding between the radionuclide fluorine-18 and a peptide functionalized. New peptides radiolabeling strategies have been developed sourcing increase the synthesis yield, its chemoselectivity, and the binding stability, and reduce the total process time and the number of steps required. The progress of radiofluorination methodologies led to development of the amidation, acylation, imidation, and alkylation techniques, the use of thiol groups, photochemical conjugation, chemoselective reactions, and “click chemistry”, in addition to use of FDG molecule and heteroatoms as linkers. This paper presents the main strategies used for peptides radiofluorination, presenting their positive and negative points, and the prosthetic groups most used in each method.