Thoracic aortic microcalcification activity in combined positron emission tomography and magnetic resonance imaging.

INTRODUCTION: Non-invasive detection of pathological changes in thoracic aortic disease remains an unmet clinical need particularly for patients with congenital heart disease. Positron emission tomography combined with magnetic resonance imaging (PET-MRI) could provide a valuable low-radiation method of aortic surveillance in high-risk groups. Quantification of aortic microcalcification activity using sodium [18F]fluoride holds promise in the assessment of thoracic aortopathies. We sought to evaluate aortic sodium [18F]fluoride uptake in PET-MRI using three methods of attenuation correction compared to positron emission tomography computed tomography (PET-CT) in patients with bicuspid aortic valve, METHODS: Thirty asymptomatic patients under surveillance for bicuspid aortic valve disease underwent sodium [18F]fluoride PET-CT and PET-MRI of the ascending thoracic aorta during a single visit. PET-MRI data were reconstructed using three iterations of attenuation correction (Dixon, radial gradient recalled echo with two [RadialVIBE-2] or four [RadialVIBE-4] tissue segmentation). Images were qualitatively and quantitatively analysed for aortic sodium [18F]fluoride uptake on PET-CT and PET-MRI. RESULTS: Aortic sodium [18F]fluoride uptake on PET-MRI was visually comparable with PET-CT using each reconstruction and total aortic standardised uptake values on PET-CT strongly correlated with each PET-MRI attenuation correction method (Dixon R = 0.70; RadialVIBE-2 R = 0.63; RadialVIBE-4 R = 0.64; p < 0.001 for all). Breathing related artefact between soft tissue and lung were detected using Dixon and RadialVIBE-4 but not RadialVIBE-2 reconstructions, with the presence of this artefact adjacent to the atria leading to variations in blood pool activity estimates. Consequently, quantitative agreements between radiotracer activity on PET-CT and PET-MRI were most consistent with RadialVIBE-2. CONCLUSION: Ascending aortic microcalcification analysis in PET-MRI is feasible with comparable findings to PET-CT. RadialVIBE-2 tissue attenuation correction correlates best with the reference standard of PET-CT and is less susceptible to artefact. There remain challenges in segmenting tissue types in PET-MRI reconstructions, and improved attenuation correction methods are required.

Coronary sodium [18F]fluoride activity predicts outcomes post-CABG: a comparative evaluation with conventional metrics.

PURPOSE: The value of preoperative multidisciplinary approach remains inadequately delineated in forecasting postoperative outcomes of patients undergoing coronary artery bypass grafting (CABG). Herein, we aimed to ascertain the efficacy of multi-modality cardiac imaging in predicting post-CABG cardiovascular outcomes. METHODS: Patients with triple coronary artery disease underwent cardiac sodium [18F]fluoride ([18F]NaF) positron emission tomography/computed tomography (PET/CT), coronary angiography, and CT-based coronary artery calcium scoring before CABG. The maximum coronary [18F]NaF activity (target-to-blood ratio [TBR]max) and the global coronary [18F]NaF activity (TBRglobal) was determined. The primary endpoint was perioperative myocardial infarction (PMI) within 7-day post-CABG. Secondary endpoint included major adverse cardiac and cerebrovascular events (MACCEs) and recurrent angina. RESULTS: This prospective observational study examined 101 patients for a median of 40 months (interquartile range: 19-47 months). Both TBRmax (odds ratio [OR] = 1.445; p = 0.011) and TBRglobal (OR = 1.797; P = 0.018) were significant predictors of PMI. TBRmax>3.0 (area under the curve [AUC], 0.65; sensitivity, 75.0%; specificity, 56.8%; p = 0.036) increased PMI risk by 3.661-fold, independent of external confounders. Kaplan-Meier test revealed a decrease in MACCE survival rate concomitant with an escalating TBRmax. TBRmax>3.6 (AUC, 0.70; sensitivity, 76.9%; specificity, 73.9%; p = 0.017) increased MACCEs risk by 5.520-fold. Both TBRmax (hazard ratio [HR], 1.298; p = 0.004) and TBRglobal (HR = 1.335; p = 0.011) were significantly correlated with recurrent angina. No significant associations were found between CAC and SYNTAX scores and between PMI occurrence and long-term MACCEs. CONCLUSION: Quantification of coronary microcalcification activity via [18F]NaF PET displayed a strong ability to predict early and long-term post-CABG cardiovascular outcomes, thereby outperforming conventional metrics of coronary macrocalcification burden and stenosis severity. TRIAL REGISTRATION: The trial was registered with the Chinese Clinical Trial Committee (number: ChiCTR1900022527; URL: www.chictr.org.cn/showproj.html?proj=37933 ).

Automation of Copper-Mediated 18F-Fluorination of Aryl Pinacol Boronates Using 4-Dimethylaminopyridinium Triflate.

Currently, the copper-mediated radiofluorination of aryl pinacol boronates (arylBPin) using the commercially available, air-stable Cu(OTf)2Py4 catalyst is one of the most efficient synthesis approaches, greatly facilitating access to a range of radiotracers, including drug-like molecules with nonactivated aryl scaffolds. Further adjustment of this methodology, in particular, the [18F]fluoride recovery step for the routine preparation of radiotracers, has been the focus of recent research. In our recent study, an organic solution of 4-dimethylaminopyridinium trifluoromethanesulfonate (DMAPOTf) was found to be an efficient PTC for eluting radionuclides retained on the weak anion exchange cartridge, Oasis WAX 1cc, employing the inverse sorption-elution protocol. Notably, the following Cu-mediated radiofluorination of arylBPin precursors in the presence of the Cu(OTf)2(Py)4 catalyst can be performed with high efficiency in the same solvent, bypassing not only the conventional azeotropic drying procedure but any solvent replacement. In the current study, we aimed to translate this methodology, originally developed for remote-controlled operation with manual interventions, into the automated synthesis module on the TRACERlab automation platform. The adjustment of the reagent amounts and solvents allowed for high efficiency in the radiofluorination of a series of model arylBPin substrates on the TRACERlab FXFE Pro synthesis module, which was adapted for nucleophilic radiofluorinations. The practical applicability of the developed radiofluorination approach with DMAPOTf elution was demonstrated in the automated synthesis of 6-L-[18F]FDOPA. The radiotracer was obtained with an activity yield (AY; isolated, not decay-corrected) of 5.2 ± 0.5% (n = 3), with a synthesis time of ca. 70 min on the TRACERlab FX N Pro automation platform. The obtained AY was comparable with one reported by others (6 ± 1%) using the same boronate precursor, while a slightly higher AY of 6-L-[18F]FDOPA (14.5 ± 0.5%) was achieved in our previous work using commercially available Bu4NOTf as the PTC.

Development of an 18F-labeled anti-human CD8 VHH for same-day immunoPET imaging.

PURPOSE: Cancer immunotherapies (CITs) have revolutionized the treatment of certain cancers, but many patients fail to respond or relapse from current therapies, prompting the need for new CIT agents. CD8+ T cells play a central role in the activity of many CITs, and thus, the rapid imaging of CD8+ cells could provide a critical biomarker for new CIT agents. However, existing 89Zr-labeled CD8 PET imaging reagents exhibit a long circulatory half-life and high radiation burden that limit potential applications such as same-day and longitudinal imaging. METHODS: To this end, we discovered and developed a 13-kDa single-domain antibody (VHH5v2) against human CD8 to enable high-quality, same-day imaging with a reduced radiation burden. To enable sensitive and rapid imaging, we employed a site-specific conjugation strategy to introduce an 18F radiolabel to the VHH. RESULTS: The anti-CD8 VHH, VHH5v2, demonstrated binding to a membrane distal epitope of human CD8 with a binding affinity (KD) of 500 pM. Subsequent imaging experiments in several xenografts that express varying levels of CD8 demonstrated rapid tumor uptake and fast clearance from the blood. High-quality images were obtained within 1 h post-injection and could quantitatively differentiate the tumor models based on CD8 expression level. CONCLUSION: Our work reveals the potential of this anti-human CD8 VHH [18F]F-VHH5v2 to enable rapid and specific imaging of CD8+ cells in the clinic.

[18F]Fluoride PET provides distinct information on disease activity in ankylosing spondylitis as compared to MRI and conventional radiography.

PURPOSE: To relate [18F]fluoride uptake on PET with abnormalities on magnetic resonance imaging (MRI) and conventional radiography (CR) in ankylosing spondylitis (AS) patients. METHODS: Ten clinically active AS patients (female 6/10, age 38 ± 11 years) were included, and both spine and SI-joints were examined. PET scans were dichotomously scored for enhanced [18F]fluoride uptake, MRI scans were scored for fatty lesions, erosions, ankylosis, and bone marrow edema (BME), and CR was scored for erosions, syndesmophytes, and ankylosis. The overlap of lesions across all modalities was evaluated through univariate and multivariate analyses using a generalized mixed model. RESULTS: In the spine, 69 lesions with enhanced [18F]fluoride uptake, 257 MRI lesions, and 88 CR lesions were observed. PET lesions were mostly located in costovertebral and facet joints, outside the field of view (FOV) of the MRI and CR. However, PET lesions inside the FOV of MRI and CR partially showed no abnormality on MRI and CR. In lesions with abnormalities on multiple modalities, both univariate and multivariate analysis showed that PET activity had the strongest association with BME on MRI and ankylosis on CR. In the SI joints, 15 lesions (75%) with PET uptake were found, with 87% showing abnormalities on MRI and CR. CONCLUSION: [18F]fluoride PET lesions are often found outside the scope of MRI and CR, and even in the same location show only partial overlap with abnormalities on MRI (especially BME) and CR (especially ankylosis). This suggests that [18F]fluoride PET partially visualizes aspects of AS separate from MRI and CR, providing novel information. CLINICAL TRIAL REGISTRATION: NL43223.029.13 registered at 02-05-2013.  https://www.toetsingonline.nl/to/ccmo_search.nsf/fABRpop?readform&unids=C1257BA2002CC066C1257B4E0049A65A.

Imidazolium-methylene-trifluoroborate: A novel radioprosthetic group validated with preclinical 18 F-Positron Emission Tomography imaging of Prostate Specific Membrane Antigen in mice.

Organotrifluoroborates have gained acceptance as radioprosthetic groups for radiofluorination. Of these, the zwitterionic prosthetic group "AMBF3 " with a quaternary dimethylammonium ion dominates the trifluoroborate space. Herein, we report on imidazolium-methylene trifluoroborate (ImMBF3 ) as an alternative radioprosthetic group and report on its properties in the context of a PSMA-targeting EUK ligand that was previously been conjugated to AMBF3 . The ImMBF3 is readily synthesized from imidazole and conjugated via CuAAC "click" chemistry to give a structure similar to PSMA-617. 18 F-labeling proceeded in one step per our previous reports and imaged in LNCaP-xenograft bearing mice. The [18 F]-PSMA-617-ImMBF3 tracer proved to be less polar (LogP7.4 = -2.95 ± 0.03) while showing a significantly lower solvolytic rate (t1/2 = 8100 min) and slightly higher molar activity (Am) at 174 ± 38 GBq/µmol. Tumor uptake was measured at 13.7 ± 4.8%ID/g and a tumor:muscle ratio of 74.2 ± 35.0, tumor:blood ratio of 21.4 ± 7.0, tumor:kidney ratio of 0.29 ± 0.14, and tumor:bone ratio of 23.5 ± 9.5. In comparison with previously reported PSMA-targeting EUK-AMBF3 conjugates, we have altered the LogP7.4 value, tuned the solvolytic half-life of the prosthetic, and increased radiochemical conversion while achieving similar tumor uptake, contrast ratios, and molar activities compared with AMBF3 bioconjugates.

18F-fluoride PET/MR in cardiac amyloid: A comparison study with aortic stenosis and age- and sex-matched controls.

OBJECTIVES: Cardiac MR is widely used to diagnose cardiac amyloid, but cannot differentiate AL and ATTR subtypes: an important distinction given their differing treatments and prognoses. We used PET/MR imaging to quantify myocardial uptake of 18F-fluoride in ATTR and AL amyloid patients, as well as participants with aortic stenosis and age/sex-matched controls. METHODS: In this prospective multicenter study, patients were recruited in Edinburgh and New York and underwent 18F-fluoride PET/MR imaging. Standardized volumes of interest were drawn in the septum and areas of late gadolinium enhancement to derive myocardial standardized uptake values (SUV) and tissue-to-background ratio (TBRMEAN) after correction for blood pool activity in the right atrium. RESULTS: 53 patients were scanned: 18 with cardiac amyloid (10 ATTR and 8 AL), 13 controls, and 22 with aortic stenosis. No differences in myocardial TBR values were observed between participants scanned in Edinburgh and New York. Mean myocardial TBRMEAN values in ATTR amyloid (1.13 ± 0.16) were higher than controls (0.84 ± 0.11, P = .0006), aortic stenosis (0.73 ± 0.12, P < .0001), and those with AL amyloid (0.96 ± 0.08, P = .01). TBRMEAN values within areas of late gadolinium enhancement provided discrimination between patients with ATTR (1.36 ± 0.23) and all other groups (e.g., AL [1.06 ± 0.07, P = .003]). A TBRMEAN threshold >1.14 in areas of LGE demonstrated 100% sensitivity (CI 72.25 to 100%) and 100% specificity (CI 67.56 to 100%) for ATTR compared to AL amyloid (AUC 1, P = .0004). CONCLUSION: Quantitative 18F-fluoride PET/MR imaging can distinguish ATTR amyloid from other similar phenotypes and holds promise in improving the diagnosis of this condition.

Electrochemical Radiofluorination of Small Molecules: New Advances.

The development of new 18 F-based radiopharmaceuticals constantly demands innovations in the search for new radiofluorination methods. [18 F]fluoride is the simplest and most convenient chemical form of the isotope for the synthesis of 18 F-based radiopharmaceuticals. The ease of production and handling, as well as the possibility of obtaining high molar activities, makes it the preferred choice for radiofluorination. However, the use of [18 F]fluoride in late-stage radiofluorination comes with challenges, especially for the radiolabeling of electron-rich molecules where SN 2 and SN Ar reactions are not suitable. New developments in fluorination chemistry have been extensively studied to overcome these difficulties. Selective electrochemical oxidation of precursors, using a controlled potential, is one method to create reactive intermediates and overcome the activation energy required for nucleophilic fluorination of electron-rich moieties. This method has been used for years in cold fluorination of organic molecules and more recently has been adapted as an alternative to traditional radiofluorination methods. Although relatively young, this field stands out as a promising route for the synthesis of new PET probes as well as fluorinated pharmaceuticals. This review focuses on recent advances in electrochemical radiofluorination as an alternative for the late-stage radiolabeling of organic molecules.

One-step radiosynthesis and initial evaluation of a small molecule PET tracer for PD-L1 imaging.

Programmed cell death protein-ligand 1 (PD-L1) is a crucial biomarker in immunotherapy and its expression level plays a key role in the guidance of anti-PD-L1 therapy. It had been reported that PD-L1 was quantified by noninvasive imaging with more developed radiotracers. In our study, a novel [18F]fluoride labeled small molecule inhibitor, [18F]LN was designed for positron emission tomography (PET) imaging in both PD-L1 transfected (A375-hPD-L1) and non-transfected (A375) melanoma-bearing mice. LN showed the specificity (IC50 = 50.39 ± 2.65 nM) to PD-L1 confirmed by competitive combination and cell flow cytometry (FACS) analysis. The radiotracer [18F]LN was obtained via 18F-19F isotope exchange from precursor LN. After radiosynthesis, [18F]LN was achieved with a high radiochemical purity (RCP) above 95% and got a favorable molar activity of 36.34 ± 5.73 GBq/µmol. [18F]LN displayed the moderate affinity (Kd = 65.27 ± 3.47 nM) to PD-L1 by specific binding assay. And it showed 1.3-fold higher uptake in A375-hPD-L1 cells than that in A375 cells. PET imaging revealed that [18F]LN could enter into PD-L1 expressing tumor site and visualize the outline of tumor. And tumor uptake (1.96 ± 0.27 %ID/g) reached the maximum at 15 min in the positive group, showed 2.2-fold higher than the negative (0.89 ± 0.31 %ID/g) or the blocked (1.07 ± 0.26 %ID/g) groups. Meanwhile, biodistribution could slightly distinguish the positive from the negative. The results indicated [18F]LN would become an efficient tool for evaluating PD-L1 expression with further optimization.

A concisely automated synthesis of TSPO radiotracer [18 F]FDPA based on spirocyclic iodonium ylide method and validation for human use.

Fluorine-18 labeled N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide ([18 F]FDPA) is a potent and selective radiotracer for positron-emission tomography (PET) imaging of the translocator protein 18 kDa (TSPO). Our previous in vitro and in vivo evaluations have proven that this tracer is promising for further human translation. Our study addresses the need to streamline the automatic synthesis of this radiotracer to make it more accessible for widespread clinical evaluation and application. Here, we successfully demonstrate a one-step radiolabeling of [18 F]FDPA based on a novel spirocyclic iodonium ylide (SCIDY) precursor using tetra-n-butyl ammonium methanesulfonate (TBAOMs), which has demonstrated the highest radiochemical yields and molar activity from readily available [18 F]fluoride ion. The nucleophilic radiofluorination was completed on a GE TRACERlab FX2 N synthesis module, and the formulated [18 F]FDPA was obtained in nondecay corrected (n.d.c) radiochemical yields of 15.6 ± 4.2%, with molar activities of 529.2 ± 22.5 GBq/µmol (14.3 ± 0.6 Ci/µmol) at the end of synthesis (60 minutes, n = 3) and validated for human use. This methodology facilitates efficient synthesis of [18 F]FDPA in a commercially available synthesis module, which would be broadly applicable for routine production and widespread clinical PET imaging studies.

Partial volume correction for improved PET quantification in 18F-NaF imaging of atherosclerotic plaques.

BACKGROUND: Accurate quantification of plaque imaging using 18F-NaF PET requires partial volume correction (PVC). METHODS: PVC of PET data was implemented by the use of a local projection (LP) method. LP-based PVC was evaluated with an image quality (NEMA) and with a thorax phantom with "plaque-type" lesions of 18-36 mL. The validated PVC method was then applied to a cohort of 17 patients, each with at least one plaque in the carotid or ascending aortic arteries. In total, 51 calcified (HU > 110) and 16 non-calcified plaque lesions (HU < 110) were analyzed. The lesion-to-background ratio (LBR) and the relative change of LBR (ΔLBR) were measured on PET. RESULTS: Following PVC, LBR of the spheres (NEMA phantom) was within 10% of the original values. LBR of the thoracic lesions increased by 155% to 440% when the LP-PVC method was applied to the PET images. In patients, PVC increased the LBR in both calcified [mean = 78% (-8% to 227%)] and non-calcified plaques [mean = 41%, (-9%-104%)]. CONCLUSIONS: PVC helps to improve LBR of plaque-type lesions in both phantom studies and clinical patients. Better results were obtained when the PVC method was applied to images reconstructed with point spread function modeling.

Automated production of [18 F]FTHA according to GMP.

14-(R,S)-[18 F]fluoro-6-thia-heptadecanoic acid is a tracer for fatty acid imaging by positron emission tomography. High demand for this tracer required us to replace semiautomatic synthesis with a fully automated procedure. An automated synthesis device was constructed in-house for multistep nucleophilic 18 F-fluorination and a control system was developed. The synthesis device was combined with a sterile filtration unit and both were qualified. 14-(R,S)-[18 F]fluoro-6-thia-heptadecanoic acid was produced according to good manufacturing practice guidelines set by the European Union. The synthesis includes an initial nucleophilic labelling reaction, deprotection, preparative HPLC separation, purification of the final product, and formulation for injection. The duration and temperature of the reaction and hydrolysis were optimized, and the radiochemical stability of the formulated product was determined. The rotary evaporator used to evaporate the solvent after HPLC purification was replaced with solid phase extraction purification. We also replaced the human serum albumin used in the earlier procedure with a phosphate buffer-ascorbic acid mixture in the final formulation solution. From 2011 to 2016, we performed 219 synthesis procedures, 94% of which were successful. The radiochemical yield of 14-(R,S)-[18 F]fluoro-6-thia-heptadecanoic acid, decay-corrected to the end of bombardment, was 13% ± 6.3%. The total amount of formulated end product was 1.7 ± 0.8 GBq at end of synthesis.

Practical microscale one-pot radiosynthesis of 18 F-labeled probes.

High specific activity is often a significant requirement for radiopharmaceuticals. To achieve that with fluorine-18 (18 F)-labeled probes, it is mandatory to start from no-carrier-added fluoride and to reduce to a minimum the amount of precursor in order to decrease the presence of any pseudocarrier. In the present study, a feasible and efficient method for microscale one-pot radiosynthesis of 18 F-labeled probes is described. It allows a substantial reduction in precursor, solvent, and reagents, thus reducing also possible side reaction in the case of base-sensitive precursors. The method is based on the use of a small amount of Kryptofix 2.2.2/potassium [18 F]fluoride in MeOH (K.222/K[18 F]F-MeOH) obtained using Oasis MAX and MCX cartridges. Five methods, differing in terms of MeOH evaporation and precursor addition, for the radiosynthesis of [18 F]fallypride and [18 F]FET in ≤50-µL scale, were examined and evaluated. The method using the addition of DMSO to the K.222/K[18 F]F-MeOH solution prior to MeOH evaporation is proposed as a versatile procedure for feasible one-pot 10- to 20-µL scale radiosyntheses. This method was successfully applied also to the radiosynthesis of [18 F]FES, [18 F]FLT, and [18 F]FMISO, with radiochemical yields comparable with those reported in the literature. Purification of a crude product by an analytical HPLC column was also demonstrated.

Quantitative in vivo fusion assessment by (18)F-fluoride PET/CT following en bloc spondylectomy.

PURPOSE: The purpose of this retrospective analyses was to evaluate the bone viability in the ventral column of the spine following large segmental defect reconstructions. Osseous integration of implants following spinal fusion procedures is an essential precondition to provide adequate mechanical strength to any applied forces and subsequently satisfying patient outcomes. Although CT scan is the non-invasive gold standard for fusion assessment, it lacks the ability to visualize bone viability and, therefore, discrepancy remains about sensitivity and specificity of CT as evaluation tool of spinal fusion. METHODS: A novel modality, (18)F Fluoride PET/CT, specifically allows quantitative in vivo evaluation of metabolic activity of the osseous integration. Bone viability following large segmental reconstructions in patients after mono- and multi-level en bloc spondylectomies (EBS) was analyzed. Spinal fusion was assessed on plain radiographs and CT scans according to the FDA fusion criteria as well as (18)F PET/CT. RESULTS: A total of eight patients underwent (18)F PET/CT were included (one 4-level-, one 3-level, two 2-level and four 1-level EBS). The average follow-up between EBS and radiographic studies was 24.8 months. On plain radiographs and CT scans, successful fusion was confirmed in all patients. However, (18)F PET/CT showed non-union in all cases. The metabolic bone activity within the cage was fourfold decreased compared to the reference vertebra, whereas the metabolic activity of the adjacent endplates was 1.6-fold increased compared to the reference vertebra. CONCLUSION: This study suggests a discrepancy between fusion rates assessed by plain radiographs and CT scan compared to (18)F PET/CT.

Pseudarthrosis after lumbar spinal fusion: the role of ¹8F-fluoride PET/CT.

PURPOSE: Painful pseudarthrosis is one of the most important indications for (revision) surgery after spinal fusion procedures. If pseudarthrosis is the source of recurrent pain it may require revision surgery. It is therefore of great clinical importance to ascertain if it is the source of such pain. The correlation between findings on conventional imaging (plain radiography and CT) and clinical well-being has been shown to be moderate. The goal of this study was to determine the possible role of (18)F-fluoride PET in patients after lumbar spinal interbody fusion by investigating the relationship between PET/CT findings and clinical function and pain. METHODS: A cohort of 36 patients was retrospectively included in the study after (18)F-fluoride PET/CT for either persistent or recurrent low back pain (18 patients) or during routine postoperative investigation (18 patients) between 9 and 76 months and 11 and 14 months after posterior lumbar interbody fusion, respectively. Sixty minutes after intravenous injection of 156 - 263 MBq (mean 199 MBq, median 196 MBq) (18)F-fluoride, PET and CT images were acquired using an integrated PET/CT scanner, followed by a diagnostic CT scan. Two observers independently scored the images. The number of bony bridges between vertebrae was scored on the CT images to quantify interbody fusion (0, 1 or 2). Vertebral endplate and intervertebral disc space uptake were evaluated visually as well as semiquantitatively following (18)F-fluoride PET. Findings on PET and CT were correlated with clinical wellbeing as measured by validated questionnaires concerning general daily functioning (Oswestry Disability Index), pain (visual analogue scale) and general health status (EuroQol). Patients were divided into three categories based on these questionnaire scores. RESULTS: No correlation was found between symptom severity and fusion status. However, (18)F-fluoride activity in the vertebral endplates was significantly higher in patients in the lowest Oswestry Disability Index category (i.e. with the worst clinical performance) than in patients in higher categories (p = 0.01 between categories 1 and 2 and 1 and 3). The visual analogue scale and EuroQol results were similar although less pronounced, with only SUVmax between category 1 and 2 being significantly different (p = 0.04). CONCLUSION: We hypothesize that (18)F-fluoride PET/CT may be able to provide support for the diagnosis of painful pseudarthrosis and could serve as a tool to discriminate between symptomatic and asymptomatic pseudarthrosis for revision surgery, as CT defines the consolidation status and PET pinpoints the 'stress reaction' at the vertebral endplates which significantly correlates with Oswestry Disability Index score.

Use of 18F-fluoride positron emission tomography as a predictor of the hip osteoarthritis progression.

OBJECTIVE: The prediction of hip osteoarthritis (OA) progression is still a difficult issue. We have adopted (18)F-fluoride positron emission tomography (PET) for the evaluation of hip osteoarthritis, and investigated the prediction utility of (18)F-fluoride PET for both pain worsening and OA progression using a logistic regression model. MATERIALS AND METHODS: A total of 57 hip joints were analyzed for progression risk factors for pain worsening and minimum joint space (MJS) narrowing by logistic regression analysis. Sex, age, BMI, existence of pain, the PET maximum standardized uptake value (SUV(max)), Kellgren and Lawrence grade, MJS, and follow-up period were used as explanatory variables. Receiver operating characteristic analysis was performed to calculate the cutoff value of the SUV(max). RESULTS: Multivariate logistic regression analysis revealed significant differences only in the SUV(max) values for pain worsening and MJS narrowing. The odds ratio of the SUV(max) for pain worsening was 1.89, and for MJS narrowing it was 11.02. The SUV(max) cutoff value was 7.2 (sensitivity: 1.00, specificity: 0.84) for pain worsening and 6.4 (sensitivity: 0.92, specificity: 0.83) for MJS narrowing. CONCLUSIONS: Our results indicate that the PET SUV(max) is a best predictor of pain worsening and MJS narrowing. This imaging modality has a great potential for the prediction of OA progression.

(18)F-Labeling of Aryl-SCF3, -OCF3 and -OCHF2 with [(18)F]Fluoride.

We report that halogenophilic silver(I) triflate permits halogen exchange (halex) nucleophilic (18)F-fluorination of aryl-OCHFCl, -OCF2Br and -SCF2Br precursors under mild conditions. This Ag(I)-mediated process allows for the first time access to a range of (18)F-labeled aryl-OCHF2, -OCF3 and -SCF3 derivatives, inclusive of [(18)F]riluzole. The (18)F-labeling of these medicinally important motifs expands the radiochemical space available for PET applications.

The Use of 18F-Fluoride Positron Emission Tomography/Computed Tomography Scanning to Identify Sources of Pain after Posterior Lumbar Interbody Fusion-An Analysis in Patients with and without Symptoms.

BACKGROUND: Identifying the cause of recurrent or persisting pain after posterior lumbar interbody fusion (PLIF) is essential for establishing optimal treatment. In this study, we evaluate patients after PLIF surgery by 18F-fluoride PET/CT scans and patient-reported outcome measures (PROMs). METHODS: A total of 36 PLIF patients were included. Sixty minutes after intravenous injection of 18F-fluoride, PET/CT scanning was performed. Bone graft ingrowth, subsidence, screw loosening and damage of facet joints were scored by quantifying the level of bone metabolism of the vertebral endplates in the disc spaces, around screws and around the facet joints on the PET scans. RESULTS: In contrast to asymptomatic patients, symptomatic patients showed abnormal PET values around pedicle screws and/or facet joints and at the lower endplates of the disc spaces, identifying a possible source of pain. On CT, no significant differences between these two groups were found. CONCLUSION: The PET/CT findings appeared to correlate better with symptoms on PROMs compared to CT findings alone. When interpreting 18F-fluoride PET/CT findings after PLIF surgery, one should realize bone metabolism in the disc spaces of the operated segments and around pedicle screws or facet joint changes during follow-up, reflecting natural recovery.

Diagnostic performance of 18F­FDG PET/CT vs. 18F­NaF PET/CT in breast cancer with bone metastases: An indirect comparative meta­analysis.

Breast cancer remains the leading cause of cancer-related death in women, with 5-year survival rates of as high as 90% for patients with early-stage breast cancer without metastasis, falling to 10% once bone metastases (BM) occur. Currently, there is no cure for breast cancer with BM. However, appropriate treatment can extend survival and improve patients' quality of life. Therefore, it is important to accurately evaluate the presence of BM in patients with breast cancer. The present meta-analysis evaluated the diagnostic performance of 18F-FDG and 18F-NaF as PET/CT tracers for breast cancer-associated BM. The present study aimed to compare the diagnostic performance of fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomographs (PET/CT) and 18F-sodium fluoride (18F-NaF) PET/CT in patients with breast cancer and BM. The PubMed and Embase databases were searched for English literature on the diagnostic performance of 18F-FDG PET/CT and 18F-NaF PET/CT for breast cancer BM, and two authors independently extracted data. All included studies presented data that could be used to construct a 2×2 contingency table. The methodological quality of the selected studies was assessed using QUADAS-2, and forest plots were generated based on the sensitivity and specificity of 18F-FDG PET/CT and 18F-NaF PET/CT in the diagnosis of BM associated with breast cancer. A total of 14 articles were identified, including eight on the analysis of 18F-FDG PET/CT, five on 18F-NaF PET/CT and one on both. The studies on 18F-FDG PET/CT and 18F-NaF PET/CT included 530 and 270 patients, respectively. The pooled sensitivities were 0.88 [95% confidence interval (95% CI), 0.76-0.94] for 18F-FDG PET/CT and 0.98 (95% CI, 0.92-1.00) for 18F-NaF PET/CT, and the pooled specificities were 0.99 (95% CI, 0.97-1.00) and 0.91 (95% CI: 0.76-0.97), respectively. The area under the summary receiver operating characteristic curve for both 18F-FDG PET/CT and 18F-NaF PET/CT was 0.99 (95% CI, 0.98-1.00). Lesion-based analysis using 18F-FDG PET/CT was performed for 909 lesions, with a sensitivity of 0.84 (95% CI, 0.67-1.00) and specificity of 1.00 (95% CI, 0.98-1.00). Compared with 18F-FDG PET/CT, 18F-NaF PET/CT showed higher sensitivity (98 vs. 88%) but lower specificity (91 vs. 99%), although the difference between methods was not statistically significant. In conclusion, the results of the present study indicated that 18F-NaF PET/CT and 18F-FDG PET/CT are both accurate methods for the detection of BM in patients with breast cancer, and have comparable diagnostic accuracy.