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).

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.

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.

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.

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.

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.

Drug-induced cardiomyopathy:Characterization of a rat model by[^18 F]FDG/PET and[^99m Tc]MIBI/SPECT

Background:Drug-induced cardiomyopathy is a significant medical problem.Clinical diagnosis of myocardial injury is based on initial electrocardiogram,levels of circulating biomarkers,and perfusion imaging with single photon emission computed tomography(SPECT).Positron emission tomography(PET)is an alternative imaging modality that provides better resolution and sensitivity than SPECT,improves diagnostic accuracy,and allows therapeutic monitoring.The objective of this study was to assess the detection of drug-induced cardiomyopathy by PET using 2-deoxy-2-[^18F]fluoro-D-glucose(FDG)and compare it with the conventional SPECT technique with[^99m Tc]-Sestamibi(MIBI).Methods:Cardiomyopathy was induced in Sprague Dawley rats using high-dose isoproterenol.Nuclear[^18F]FDG/PET and[^99m Tc]MIBI/SPECT were performed before and after isoproterenol administration.[^18F]FDG(0.1 mCi,200-400μL)and[^99m Tc]MIBI(2 mCi,200-600μL)were administered via the tail vein and imaging was performed 1 hour postinjection.Isoproterenol-induced injury was confirmed by the plasma level of cardiac troponin and triphenyltetrazolium chloride(TTC)staining.Results:Isoproterenol administration resulted in an increase in circulating cardiac troponin I and showed histologic damage in the myocardium.Visually,preisoproterenol and postisoproterenol images showed alterations in cardiac accumulation of[^18F]FDG,but not of[^99m Tc]MIBI.Image analysis revealed that myocardial uptake of[^18F]FDG reduced by 60%after isoproterenol treatment,whereas that of[^99m Tc]MIBI decreased by 45%.Conclusion:We conclude that[^18F]FDG is a more sensitive radiotracer than[^99m Tc]MIBI for imaging of drug-induced cardiomyopathy.We theorize that isoproterenolinduced cardiomyopathy impacts cellular metabolism more than perfusion,which results in more substantial changes in[^18F]FDG uptake than in[^99m Tc]MIBI accumulation in cardiac tissue.

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.

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.

Mapping Changes of Whole Brain Blood Flow in Rats with Myocardial Ischemia/Reperfusion Injury Assessed by Positron Emission Tomography

l8F-labeled fluorodeoxyglucose positron emission tomography (l8F-FDG PET) is the most sensitive tool for studying brain metabolism in vivo.We investigated the image patterns of 18F-FDG PET during reperfusion injury and correlated changes of whole brain blood flow utilizing a rat myocardial ischemia/reperfiision injury (MIRI) model.The results assessed by echocardiography indicated resultant cardiac dysfunction after ischemia-reperfusion in the rat heart.It was found that the average standardized uptake value (SUVaverage) of the whole brain was significantly decreased in model rats,and the glucose uptake of different brain regions including accumbens core/shell (Acb),left caudate putamen (LCPu),hippocampus (HIP),left hypothalamus (LHYP),olfactory (OLF),superior colliculus (SC),right midbrain (RMID),ventral tegmental area (VTA),inferior colliculus (IC) and left thalamus whole (LTHA) was significantly decreased in MIRI rats whereas no significant difference was found in the SUVaverage of amygdala (AMY),right Cpu,RHYP,right HYP,left MID,right THA,pons and medulla oblongata (MO).These l8F-FDG PET data provide a reliable identification method for brain metabolic changes in rats with MIRI.

Multimodality imaging in the diagnosis and management of prosthetic valve endocarditis:A contemporary narrative review

Infective endocarditis is one of the leading life-threatening infections around the world.With the exponential growth in the field of transcatheter interventions and advances in specialized surgical techniques,the number of prosthetic valves and cardiac implantable devices has significantly increased.This has led to a steep rise in the number of cases of prosthetic valve endocarditis(PVE)comprising up to 30%of all cases.Clinical guidelines rely on the use of the modified Duke criteria;however,the diagnostic sensitivity of the modified Duke criteria is reduced in the context of PVE.This is in part attributed to prosthesis related artifact which greatly affects the ability of echocardiography to detect early infective changes related to PVE in certain cases.There has been increasing recognition of the roles of complementary imaging modalities and updates in international society recommendations.Prompt diagnosis and treatment can prevent the devastating consequences of this condition.Imaging modalities such as cardiac computed tomography and 18-fluorodeoxyglucose positron emission tomography/computed tomography are diagnostic tools that provide a complementary role to echocardiography in aiding diagnosis,pre-operative planning,and treatment decisionmaking process in these challenging cases.Understanding the strengths and limitations of these adjuvant imaging modalities is crucial for the implementation of appropriate imaging modalities in clinical practice.

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.

Recent advances in photochemistry for positron emission tomography imaging

As a powerful noninvasive imaging technology,positron emission tomography(PET)has been playing an important role in disease theranostics and drug discovery.The successful application of PET relies on not only the biological properties of PET tracers but also the availability of facile and efficient radiochemical reactions to enable practical production and widespread use of PET tracers.Most recently,photochemistry is emerging as a novel,mild and efficient approach to generating PET agents.In this review,we focus on the recent advances in newly developed photocatalytic radiochemical reactions,innovation on automated photochemical radiosynthesis modules,as well as implementation in late-stage radiolabeling and radio-pharmaceutical synthesis for PET imaging.We believe that this review will inspire the development of more promising radiolabeling protocols for the preparation of clinically useful PET agents.

Discovery and development of brain-penetrant ^(18)F-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.

Synthesis and characterization of the two enantiomers of a chiral sigma-1 receptor radioligand:(S)-(+)-and(R)-(-)-[^(18)F]FBFP

Racemic[^(18)F]FBFP([^(18)F]1)proved to be a potentσ_(1) receptor radiotracer with superior imaging properties.The pure enantiomers of unlabeled compounds(S)-and(R)-1 and the corresponding iodonium ylide precursors were synthesized and characterized.The two enantiomers(S)-1 and(R)-1 exhibited comparable high affinity forσ_(1) receptors and selectivity overσ_(2) receptors.The Ca^(2+) fluorescence assay indicated that(R)-1 behaved as an antagonist and(S)-1 as an agonist forσ_(1) receptors.The ^(18)F-labeled enantiomers(S)-and(R)-[^(18)F]1 were obtained in>99%enantiomeric purity from the corresponding enantiopure iodonium ylide precursors with radiochemical yield of 24.4%±2.6%and molar activity of 86–214 GBq/μmol.In ICR mice both(S)-and(R)-[^(18)F]1displayed comparable high brain uptake,brain-to-blood ratio,in vivo stability and binding specificity in the brain and peripheral organs.In micro-positron emission tomography(PET)imaging studies in rats,(S)-[^(18)F]1 exhibited faster clearance from the brain than(R)-[^(18)F]1,indicating different brain kinetics of the two enantiomers.Both(S)-and(R)-[^(18)F]1 warrant further evaluation in primates to translate a single enantiomer with more suitable kinetics for imaging theσ_(1) receptors in humans.

Development of a highly-specific ^(18)F-labeled irreversible positron emission tomography tracer for monoacylglycerol lipase mapping

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 14 as a lead compound,which was then radiolabeled with fluorine-18 via a facile SNAr reaction to form 2-[^(18)F]fluoropyridine scaffold.Good blood-brain barrier permeability and high in vivo specific binding was demonstrated for radioligand [^(18)F]14(also named as [^(18)F]MAGL-1902).This work may serve as a roadmap for clinical translation and further design of potent 18F-labeled MAGL PET tracers.