Value of 18F-FDG pet/CT for prognostic assessment in patients with infective endocarditis.

BACKGROUND: 18F-FDG PET/CT is a valuable diagnostic tool in infective endocarditis (IE). However, the prognostic value is unclear. This study aims to evaluate the prognostic performance of 18F-FDG PET/CT in native valve endocarditis (NVE) and prosthetic valve endocarditis (PVE). METHODS: We retrospectively included 76 patients treated for definite IE (NVE and PVE) that underwent 18F-FDG PET/CT between January 2016 and December 2018. Clinical, echocardiographic and 18F-FDG PET/CT (pathologic valvular 18F-FDG uptake, extracardiac complications (ECC)) data were collected. The primary endpoint was defined as mortality or recurrence of IE at a one-year follow-up. RESULTS: Pathologic valvular 18F-FDG uptake was detected in 32 of 57 (56.1%) patients, 30% (9/30) in NVE and 85.2% (23/27) in PVE group. Atrial fibrillation (OR 3.90, 95% CI = 1.14-16.3), prior anticoagulation treatment (OR 6.37, 95% CI = 1.89-26.7), large vegetation (≥ 10 mm) (OR 4.05, 95% CI = 1.14-16.1), perivalvular complications (OR 7.22, 95% CI = 1.68-55.1) and abscess (OR 10.9, 95% CI = 1.84-283) were associated with positive PET/CT. Extracardiac complications were found in 27 of 76 (35.5%) patients, 42.9% (18/42) in the NVE and 26.5% (9/34) in the PVE group. Pathological valvular tracer uptake (HR 1.20, 95% CI = 0.43-3.37) or extracardiac complications (HR 0.58, 95% CI = 0.21-1.62) were not associated with the occurrence of the primary endpoint. CONCLUSION: Our study could not demonstrate a prognostic value of 18F-FDG PET/CT in IE, but confirms high diagnostic performance, which may compromise prognostic significance by accelerated optimal treatment because of earlier diagnostic certainty.

Design, Synthesis and Preclinical Assessment of 99mTc-iFAP for In Vivo Fibroblast Activation Protein (FAP) Imaging.

Fibroblast activation protein (FAP) is expressed in the microenvironment of most human epithelial tumors. 68Ga-labeled FAP inhibitors based on the cyanopyrrolidine structure (FAPI) are currently used for the detection of the tumor microenvironment by PET imaging. This research aimed to design, synthesize and preclinically evaluate a new FAP inhibitor radiopharmaceutical based on the 99mTc-((R)-1-((6-hydrazinylnicotinoyl)-D-alanyl) pyrrolidin-2-yl) boronic acid (99mTc-iFAP) structure for SPECT imaging. Molecular docking for affinity calculations was performed using the AutoDock software. The chemical synthesis was based on a series of coupling reactions of 6-hidrazinylnicotinic acid (HYNIC) and D-alanine to a boronic acid derivative. The iFAP was prepared as a lyophilized formulation based on EDDA/SnCl2 for labeling with 99mTc. The radiochemical purity (R.P.) was verified via ITLC-SG and reversed-phase radio-HPLC. The stability in human serum was evaluated by size-exclusion HPLC. In vitro cell uptake was assessed using N30 stromal endometrial cells (FAP positive) and human fibroblasts (FAP negative). Biodistribution and tumor uptake were determined in Hep-G2 tumor-bearing nude mice, from which images were acquired using a micro-SPECT/CT. The iFAP ligand (Ki = 0.536 nm, AutoDock affinity), characterized by UV-Vis, FT-IR, 1H-NMR and UPLC-mass spectroscopies, was synthesized with a chemical purity of 92%. The 99mTc-iFAP was obtained with a R.P. >98%. In vitro and in vivo studies indicated high radiotracer stability in human serum (>95% at 24 h), specific recognition for FAP, high tumor uptake (7.05 ± 1.13% ID/g at 30 min) and fast kidney elimination. The results found in this research justify additional dosimetric and clinical studies to establish the sensitivity and specificity of the 99mTc-iFAP.

Assessment of Cell Cytotoxicity and Comet Assay on HER2/neu Positive Cell Line Due to 111In Auger Electrons as DNA-Targeting Radioimmunoconjugate.

BACKGROUND: Breast cancer Auger electron therapy is a growing field of study in radioimmunotherapy and oncology research. Trastuzumab, a high affinity-binding monoclonal antibody against HER2/neu is which is over-expressed in breast tumors, is used in radiopharmaceutical development. OBJECTIVES: In this work, the lethal effects of 111In3+, 111In-DTPA-trastuzumab and 111In-trastuzumab coupled-nuclear localizing sequence peptide (111In-DTPA-NLS-trastuzumab) on malignant cells were studied in vitro. METHODS: DTPA-NLS-trastuzumab was prepared using sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo-SMCC) conjugation with NLS peptide in the first step, followed by conjugation with diethylenetriaminepentaacetic acid (DTPA). Both DTPA-trastuzumab and DTPA- NLS-trastuzumab were labeled with 111In followed by purification and quality control techniques. Sk-Br-3 (a HER2/neu+ cell line), was used in the cell viability assessment assay for 111In, 111In-DTPA-trastuzumab and 111In-DTPA-NLS-trastuzumab (3.7 MBq) at 37 ºC. The cytotoxicity of the three species was studied using MTT and comet assay was utilized DNA damage detection. RESULTS: A significant radiochemical purity for 111In-DTPA-NLS-trastuzumab (99.36% ± 0.30%, ITLC) at the DTPA:antibody ratio of 6.90 ± 0.34:1, was obtained. Significant cell viability difference was found for 111In-DTPA-NLS-trastuzumab compared to the other treatments at two-time points. In addition, comet assay demonstrated significant DNA damage at 144 h using 111In-DTPA- NLS-trastuzumab. CONCLUSION: The results of cell viability and cell death using MTT assay and comet assay, respectively, demonstrate the NLS-peptide effectively facilitates 111In-trastuzumab transport into the HER2/neu positive cancer cell nuclei to impose the radiotherapeutic effects of Auger electrons on DNA leading to cell death.

Preclinical Assessment of [68Ga]Ga-Cell Death Indicator (CDI): A Novel hsp90 Ligand for Positron Emission Tomography of Cell Death.

BACKGROUND: 4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid (GSAO) when conjugated with a bifunctional chelator 2,2'-(7-(1-carboxy-4-((2,5-dioxopyrrolidin-1-yl)oxy)-4- oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid (NODAGA) (hereafter referred to as Cell Death Indicator [CDI]), enters dead and dying cells and binds to 90kDa heat shock proteins (hsp90). OBJECTIVE: This study assesses stability, biodistribution, imaging, and radiation dosimetry of [68Ga]- Ga-CDI for positron emission tomography (PET). METHODS: Preparation of [68Ga]Ga-CDI was performed as previously described. Product stability and stability in plasma were assessed using high-performance liquid chromatography. Biodistribution and imaging were conducted in ten healthy male Lewis rats at 1 and 2 h following intravenous [68Ga]Ga-CDI injection. Human radiation dosimetry was estimated by extrapolation for a standard reference man and calculated with OLINDA/EXM 1.1. RESULTS: Radiochemical purity of [68Ga]Ga-CDI averaged 93.8% in the product and 86.7% in plasma at 4 h post-synthesis. The highest concentration of [68Ga]Ga-CDI is observed in the kidneys; [68Ga]Ga-CDI is excreted in the urine, and mean retained activity was 32.4% and 21.4% at 1 and 2 h post-injection. Lower concentrations of [68Ga]Ga-CDI were present in the small bowel and liver. PET CT was concordant and additionally demonstrated focal growth plate uptake. The effective dose for [68Ga]Ga-CDI is 2.16E-02 mSv/MBq, and the urinary bladder wall received the highest dose (1.65E-02 mSv/Mbq). CONCLUSION: [68Ga] Ga-CDI is stable and has favourable biodistribution, imaging, and radiation dosimetry for imaging of dead and dying cells. Human studies are underway.

Tau Biomarkers in Dementia: Positron Emission Tomography Radiopharmaceuticals in Tauopathy Assessment and Future Perspective.

Abnormal accumulation of Tau protein is closely associated with neurodegeneration and cognitive impairment and it is a biomarker of neurodegeneration in the dementia field, especially in Alzheimer's disease (AD); therefore, it is crucial to be able to assess the Tau deposits in vivo. Beyond the fluid biomarkers of tauopathy described in this review in relationship with the brain glucose metabolic patterns, this review aims to focus on tauopathy assessment by using Tau PET imaging. In recent years, several first-generation Tau PET tracers have been developed and applied in the dementia field. Common limitations of first-generation tracers include off-target binding and subcortical white-matter uptake; therefore, several institutions are working on developing second-generation Tau tracers. The increasing knowledge about the distribution of first- and second-generation Tau PET tracers in the brain may support physicians with Tau PET data interpretation, both in the research and in the clinical field, but an updated description of differences in distribution patterns among different Tau tracers, and in different clinical conditions, has not been reported yet. We provide an overview of first- and second-generation tracers used in ongoing clinical trials, also describing the differences and the properties of novel tracers, with a special focus on the distribution patterns of different Tau tracers. We also describe the distribution patterns of Tau tracers in AD, in atypical AD, and further neurodegenerative diseases in the dementia field.

Assessment of the viability and treatment response of bone metastases in patients with metastatic castration-resistant prostate cancer using choline PET/CT.

ABSTRACT: This study aimed to evaluate the clinical use of choline-PET/CT for discriminating viable progressive osteoblastic bone metastasis from benign osteoblastic change induced by the treatment effect and evaluating the response of bone metastasis to treatment in metastatic castration-resistant prostate cancer (mCRPC) patients. Thirty patients with mCRPC underwent a total of 56 11C-choline-PET/CT scans for restaging, because 4 patients received 1 scan and 26 had 2 scans. Using 2 (pre- and post-treatment) 11C-choline-PET/CT examinations per patient, treatment response was assessed according to European Organization for Research and Treatment of Cancer (EORTC) criteria in 20 situations, in which only bony metastases were observed on 11C-choline-PET/CT scans. Viable bone metastases and osteoblastic change induced by the treatment effect were identified in 53 (94.6%) and 29 (51.8%) of 56 11C-choline-PET/CT scans, respectively. In 27 cases (48.2%), 11C-choline-PET/CT scans could discriminate the 2 entities. The mean SUVmax of the metastatic bony lesions was 5.82 ±â€Š3.21, 5.95 ±â€Š3.96, 6.73 ±â€Š5.04, and 7.91 ±â€Š3.25 for the osteoblastic, osteolytic, mixed, and invisible types, respectively. Of the 20 situations analyzed, CMR, PMR, SMD, and PMD, as determined by the EORTC, were seen in 1, 2, 3, and 14 cases, respectively. Of the 13 patients with increasing PSA trend, all 13 showed PMD. Of the 2 patients with PSA response of <50%, both 2 showed SMD. Of the 5 patients with PSA response of ≥50%, 1 showed CMR, 2 showed PMR, 1 showed SMD, and 1 showed PMD. Choline-PET/CT is very useful to discriminate viable progressive osteoblastic bone metastasis from osteoblastic change, and assess treatment response of bone metastases in mCRPC.

PSMA-D4 Radioligand for Targeted Therapy of Prostate Cancer: Synthesis, Characteristics and Preliminary Assessment of Biological Properties.

A new PSMA ligand (PSMA-D4) containing the Glu-CO-Lys pharmacophore connected with a new linker system (L-Trp-4-Amc) and chelator DOTA was developed for radiolabeling with therapeutic radionuclides. Herein we describe the synthesis, radiolabeling, and preliminary biological evaluation of the novel PSMA-D4 ligand. Synthesized PSMA-D4 was characterized using TOF-ESI-MS, NMR, and HPLC methods. The novel compound was subject to molecular modeling with GCP-II to compare its binding mode to analogous reference compounds. The radiolabeling efficiency of PSMA-D4 with 177Lu, 90Y, 47Sc, and 225Ac was chromatographically tested. In vitro studies were carried out in PSMA-positive LNCaP tumor cells membranes. The ex vivo tissue distribution profile of the radioligands and Cerenkov luminescence imaging (CLI) was studied in LNCaP tumor-bearing mice. PSMA-D4 was synthesized in 24% yield and purity >97%. The radio complexes were obtained with high yields (>97%) and molar activity ranging from 0.11 to 17.2 GBq mcmol-1, depending on the radionuclide. In vitro assays confirmed high specific binding and affinity for all radiocomplexes. Biodistribution and imaging studies revealed high accumulation in LNCaP tumor xenografts and rapid clearance of radiocomplexes from blood and non-target tissues. These render PSMA-D4 a promising ligand for targeted therapy of prostate cancer (PCa) metastases.

Clinical Evaluation of a Three-Dimensional Internal Dosimetry Technique for Liver Radioembolization with 90Y Microspheres Using Dose Voxel Kernels.

Background: The purpose of this study was to develop a rapid, reliable, and efficient tool for three-dimensional (3D) dosimetry treatment planning and post-treatment evaluation of liver radioembolization with 90Y microspheres, using tissue-specific dose voxel kernels (DVKs) that can be used in everyday clinical practice. Materials and Methods: Two tissue-specific DVKs for 90Y were calculated through Monte Carlo (MC) simulations. DVKs for the liver and lungs were generated, and the dose distribution was compared with direct MC simulations. A method was developed to produce a 3D dose map by convolving the calculated DVKs with the activity biodistribution derived from clinical single-photon emission computed tomography (SPECT) or positron emission tomography (PET) images. Image registration for the SPECT or PET images with the corresponding computed tomography scans was performed before dosimetry calculation. The authors first compared the DVK convolution dosimetry with a direct full MC simulation on an XCAT anthropomorphic phantom. They then tested it in 25 individual clinical cases of patients who underwent 90Y therapy. All MC simulations were carried out using the GATE MC toolkit. Results: Comparison of the measured absorbed dose using tissue-specific DVKs and direct MC simulation on 25 patients revealed a mean difference of 1.07% ± 1.43% for the liver and 1.03% ± 1.21% for the tumor tissue, respectively. The largest difference between DVK convolution and full MC dosimetry was observed for the lung tissue (10.16% ± 1.20%). The DVK statistical uncertainty was <0.75% for both media. Conclusions: This semiautomatic algorithm is capable of performing rapid, accurate, and efficient 3D dosimetry. The proposed method considers tissue and activity heterogeneity using tissue-specific DVKs. Furthermore, this method provides results in <1 min, making it suitable for everyday clinical practice.

DaPeCa-7: comparative assessment of fluorodeoxyglucose positron emission tomography/computed tomography (CT) and conventional diagnostic CT in diagnosis of lymph node metastases, distant metastases and incidental findings in patients with invasive penile cancer.

OBJECTIVES: To evaluate diagnostic accuracy of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) compared to contrast-enhanced CT in assessment of inguinal lymph node (ILN) metastases, distant metastases and synchronous cancers in patients with penile squamous cell carcinoma (pSCC). PATIENTS AND METHODS: During a 4-year period, patients with pSCC were scheduled for FDG PET/CT prior to surgical treatment at two referral centres that manage all penile cancers in Denmark. The primary endpoint was diagnostic accuracy of FDG PET/CT and of CT alone with histopathology or Response Evaluation Criteria In Solid Tumors (RECIST) as reference. RESULTS: We evaluated 171 patients for distant metastases and synchronous incident cancers and examined 286 groins in 143 patients for LN metastases by FDG PET/CT. Six groins disclosed false negatives. FDG PET/CT sensitivity was 85.4% per patient. In 135 patients (270 groins), CT images were evaluated separately and 22 groins disclosed false negatives. CT sensitivity was 47.5% per patient. FDG PET/CT detected pSCC distant metastases in seven patients. Distant metastases from other cancers were newly detected in three patients. In eight patients, an incidental synchronous cancer was detected. Seven out of the 18 distant malignancies detected depended on FDG PET information. CONCLUSION: This study underlines the increased diagnostic accuracy of FDG PET/CT compared to CT alone in the evaluation of ILN status. In patients with palpable LNs, the advantage of FDG PET/CT over CT is less pronounced. FDG PET/CT may play a role in penile cancer evaluation.

CCR2 Positron Emission Tomography for the Assessment of Abdominal Aortic Aneurysm Inflammation and Rupture Prediction.

BACKGROUND: The monocyte chemoattractant protein-1/CCR2 (chemokine receptor 2) axis plays an important role in abdominal aortic aneurysm (AAA) pathogenesis, with effects on disease progression and anatomic stability. We assessed the expression of CCR2 in a rodent model and human tissues, using a targeted positron emission tomography radiotracer (64Cu-DOTA-ECL1i). METHODS: AAAs were generated in Sprague-Dawley rats by exposing the infrarenal, intraluminal aorta to PPE (porcine pancreatic elastase) under pressure to induce aneurysmal degeneration. Heat-inactivated PPE was used to generate a sham operative control. Rat AAA rupture was stimulated by the administration of ß-aminopropionitrile, a lysyl oxidase inhibitor. Biodistribution was performed in wild-type rats at 1 hour post tail vein injection of 64Cu-DOTA-ECL1i. Dynamic positron emission tomography/computed tomography imaging was performed in rats to determine the in vivo distribution of radiotracer. RESULTS: Biodistribution showed fast renal clearance. The localization of radiotracer uptake in AAA was verified with high-resolution computed tomography. At day 7 post-AAA induction, the radiotracer uptake (standardized uptake value [SUV]=0.91±0.25) was approximately twice that of sham-controls (SUV=0.47±0.10; P<0.01). At 14 days post-AAA induction, radiotracer uptake by either group did not significantly change (AAA SUV=0.86±0.17 and sham-control SUV=0.46±0.10), independent of variations in aortic diameter. Competitive CCR2 receptor blocking significantly decreased AAA uptake (SUV=0.42±0.09). Tracer uptake in AAAs that subsequently ruptured (SUV=1.31±0.14; P<0.005) demonstrated uptake nearly twice that of nonruptured AAAs (SUV=0.73±0.11). Histopathologic characterization of rat and human AAA tissues obtained from surgery revealed increased expression of CCR2 that was co-localized with CD68+ macrophages. Ex vivo autoradiography demonstrated specific binding of 64Cu-DOTA-ECL1i to CCR2 in both rat and human aortic tissues. CONCLUSIONS: CCR2 positron emission tomography is a promising new biomarker for the noninvasive assessment of AAA inflammation that may aid in associated rupture prediction.

Comparison between dynamic gadoxetate-enhanced MRI and 99mTc-mebrofenin hepatobiliary scintigraphy with SPECT for quantitative assessment of liver function.

OBJECTIVES: To compare Gd-EOB-DTPA dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) with 99mTc-mebrofenin hepatobiliary scintigraphy (HBS) as quantitative liver function tests for the preoperative assessment of patients undergoing liver resection. METHODS: Patients undergoing liver surgery and preoperative assessment of future remnant liver (FRL) function using 99mTc-mebrofenin HBS were included. Patients underwent DHCE-MRI. Total liver uptake function was calculated for both modalities: mebrofenin uptake rate (MUR) and Ki respectively. The FRL was delineated with both SPECT-CT and MRI to calculate the functional share. Blood samples were taken to assess biochemical liver parameters. RESULTS: A total of 20 patients were included. The HBS-derived MUR and the DHCE-MRI-derived mean Ki correlated strongly for both total and FRL function (Pearson r = 0.70, p = 0.001 and r = 0.89, p < 0.001 respectively). There was a strong agreement between the functional share determined with both modalities (ICC = 0.944, 95% CI 0.863-0.978, n = 20). There was a significant negative correlation between liver aminotransferases and bilirubin for both MUR and Ki. CONCLUSIONS: Assessment of liver function with DHCE-MRI is comparable with that of 99mTc-mebrofenin HBS and has the potential to be combined with diagnostic MRI imaging. This can therefore provide a one-stop-shop modality for the preoperative assessment of patients undergoing liver surgery. KEY POINTS: • Quantitative assessment of liver function using hepatobiliary scintigraphy is performed in the preoperative assessment of patients undergoing liver surgery in order to prevent posthepatectomy liver failure. • Gd-EOB-DTPA dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) is an emerging method to quantify liver function and can serve as a potential alternative to hepatobiliary scintigraphy. • Assessment of liver function with dynamic gadoxetate-enhanced MRI is comparable with that of hepatobiliary scintigraphy and has the potential to be combined with diagnostic MRI imaging.

Radiochemical Evaluation and In Vitro Assessment of the Targeting Ability of a Novel 99mTc-HYNIC-RGD for U87MG Human Brain Cancer Cells.

BACKGROUND: Labeled RGD peptide that specifically targets ανß3 integrin has great potential for the early diagnosis of malignant tumors.αvß3 integrin receptors appear specifically more on the surface of glioblastoma (malignant glioma) cells rather than normal cells. OBJECTIVE: The aim of this study was to identify a novel RGD that can be radiolabeled with99mTc with in vitro assessment of its targeting ability for U87MG human brain cancer cells. METHOD: Novel RGD was designed by Amino Acid retro-inversion technique. The peptide HYNIC conjugate was radiolabeled with 99mTc at 95°C for 10 min and radiochemical analysis was performed using ITLC and HPLC methods. The stability of the radiopeptide was checked in the presence of human serum at 37°C up to 24 h. Binding properties and internalization were studied with U87MG cells. RESULTS: Novel HYNIC-RGD has shown high radiochemical purity over 98%. Radioconjugate binding and internalization in U87MG cells were high and specific (13.96% and 12.38% at 4 h respectively). The radiolabeled peptide revealed good affinity for glioblastoma cells (Kd =1.46 ±0.26nM). CONCLUSION: The in vitro study demonstrated the targeting ability of novel 99mTc-HYNIC-RGD for glioblastoma cells. Therefore, more in vivo studies are required.

Comparative assessment of a 99mTc labeled H1299.2-HYNIC peptide bearing two different co-ligands for tumor-targeted imaging.

Peptides are a class of targeting agents that bind to cancer-specific cell surfaces. Since they specifically target cancer cells, they could be used as molecular imaging tools. In this study, the 15-mer peptide Ac-H1299.2 (YAAWPASGAWTGTAP) was conjugated with HYNIC via lysine amino acid on C-terminus and labeled with 99mTc using tricine and EDDA/tricine as the co-ligands. These radiotracers were evaluated for potential utilization in diagnostic imaging of ovarian cancer cells (SKOV-3). The cell-specificity of these radiolabeled peptides was determined based on their binding on an ovarian cancer cell line (SKOV-3), and displaying a low affinity for lung adenocarcinoma cell line (A549) and breast cancer cell line (MCF7). Biodistribution studies were conducted in normal mice as well as in nude mice bearing SKOV-3 ovarian cancer xenografts. HYNIC-peptide was labeled with 99mTc with more than 99% efficiency and showed high stability in buffer and serum. We observed nanomolar binding affinities for both radiolabeled peptides. The tumor uptakes were 3.27%±0.46% and 1.55%±0.20% for tricine and 2.34±1.1% and 1.09%±0.18% for EDDA/tricine at 1 and 4h after injection, respectively. A higher tumor to background ratio and lower radioactivity in the blood were observed for EDDA/tricine co-ligands, leading to clear tumor visualization in imaging with injection of this peptide. This new 99mTc-labeled peptide selectively targeted ovarian cancer and introduction of a (EDDA/tricine) as a co-ligand improved the pharmacokinetics of 99mTc-labeled H1299.2 for tumor imaging in animals.

Predictive factors associated with the progression of large-joint destruction in patients with rheumatoid arthritis after biologic therapy: A post-hoc analysis using FDG-PET/CT and the ARASHI (assessment of rheumatoid arthritis by scoring of large-joint destruction and healing in radiographic imaging) scoring method.

OBJECTIVE: To investigate the associations between large-joint damage and findings on fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) using the "assessment of rheumatoid arthritis by scoring of large-joint destruction and healing in radiographic imaging (ARASHI)" scoring system. METHODS: A total of 270 large joints (shoulders, elbows, hips, knees, and ankles) in 27 rheumatoid arthritis patients were assessed. FDG-PET/CT was performed at the initiation of biologics. Radiographs at baseline and at 3 years were evaluated using the ARASHI score. RESULTS: Radiographic progression of damage was detected in 35 by Larsen grade vs. 87 by the ARASHI score. The maximum standardized uptake value (SUVmax) at baseline, Steinbrocker stage at baseline, concomitant prednisolone use, and disease activity score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) at 6 months were significantly higher in the radiographic progression group. An SUVmax higher than 1.65 at baseline was a significant predictive factor for progressive damage at 3 years. CONCLUSIONS: The ARASHI score may allow more detailed evaluation of large joints than the Larsen method. Joint destruction is likely to have progressed at 3 years in large joints, which had a higher SUVmax at the initiation of biologics.

Role of PET-CT in the assessment of myocardial viability in patients with left ventricular dysfunction.

AIM: Role of PET-CT in assessment of myocardial viability in patients with LV dysfunction. METHODS: This prospective study included 120 patients with LV dysfunction who underwent 99mTechnetium-Sestamibi myocardial perfusion SPECT-CT and 18FFDG cardiac PET-CT. They also underwent serial echocardiography and coronary angiography along with myocardial perfusion and FDG PET study. RESULTS: Thirty-three patients had single vessel disease, 48 had triple vessel disease, and rest had double vessel disease. Among 786 segments, matched defects were seen in 432 (55%) and mismatched defects in 354 (45%) segments. 78 patients were surgically managed, and 42 were medically managed. The change in LVEF after surgical management was statistically significant compared to medical management. CONCLUSION: Viability assessment should be performed in patients who present after 12h of acute myocardial infarction or with LV dysfunction due to ischemic heart disease to decide upon appropriate surgical management.

Assessment of coronary flow reserve using a combination of planar first-pass angiography and myocardial SPECT: Comparison with myocardial (15)O-water PET.

UNLABELLED: Coronary flow reserve (CFR), defined as the ratio of maximum coronary flow increase from baseline resting blood flow, is one of the most sensitive parameters to detect early signs of coronary arteriosclerosis at the microvascular level. Myocardial perfusion PET is a well-established technology for CFR measurement, however, availability is still limited. The aim of this study is to introduce and validate myocardial flow reserve measurement by myocardial perfusion SPECT. METHODS: Myocardial perfusion SPECT at rest and ATP stress (0.16mg/Kg/min) was performed in 10 patients with known coronary artery disease. Immediately after the injection of Tc-99m sestamibi (MIBI), left ventricular (LV) dynamic planar angiographic data were obtained for 90s. Coronary flow reserve index as measured by MIBI SPECT (CFRMIBI) was calculated as follows: CFRMIBI=CmsSbmb/CmbSbms, where subscripts b, s, Cm, and Sbm indicate baseline, during stress, myocardial counts with MIBI SPECT, and integral of LV counts with first pass angiography, respectively. Additionally, standard stress/rest (15)O-water PET to estimate CFR was performed in all patients as standard of reference. RESULTS: CFRMIBI increased in conjunction with CFR, but underestimated blood flow at high flow rates. The relationship between CFRMIBI (Y) and CFRPET (X) was well fitted as follows: Y=1.40x(1-exp(1.79/x)) (r=0.84). CONCLUSIONS: The index of CFRMIBI reflects the CFR by (15)O-water PET but underestimates flow at high flows, maybe as a reflection of pharmacokinetic limitations of MIBI.

ACRIN 6684: Assessment of Tumor Hypoxia in Newly Diagnosed Glioblastoma Using 18F-FMISO PET and MRI.

PURPOSE: Structural and functional alterations in tumor vasculature are thought to contribute to tumor hypoxia which is a primary driver of malignancy through its negative impact on the efficacy of radiation, immune surveillance, apoptosis, genomic stability, and accelerated angiogenesis. We performed a prospective, multicenter study to test the hypothesis that abnormal tumor vasculature and hypoxia, as measured with MRI and PET, will negatively impact survival in patients with newly diagnosed glioblastoma. EXPERIMENTAL DESIGN: Prior to the start of chemoradiation, patients with glioblastoma underwent MRI scans that included dynamic contrast enhanced and dynamic susceptibility contrast perfusion sequences to quantitate tumor cerebral blood volume/flow (CBV/CBF) and vascular permeability (ktrans) as well as 18F-Fluoromisonidazole (18F-FMISO) PET to quantitate tumor hypoxia. ROC analysis and Cox regression models were used to determine the association of imaging variables with progression-free and overall survival. RESULTS: Fifty patients were enrolled of which 42 had evaluable imaging data. Higher pretreatment 18F-FMISO SUVpeak (P = 0.048), mean ktrans (P = 0.024), and median ktrans (P = 0.045) were significantly associated with shorter overall survival. Higher pretreatment median ktrans (P = 0.021), normalized RCBV (P = 0.0096), and nCBF (P = 0.038) were significantly associated with shorter progression-free survival. SUVpeak [AUC = 0.75; 95% confidence interval (CI), 0.59-0.91], nRCBV (AUC = 0.72; 95% CI, 0.56-0.89), and nCBF (AUC = 0.72; 95% CI, 0.56-0.89) were predictive of survival at 1 year. CONCLUSIONS: Increased tumor perfusion, vascular volume, vascular permeability, and hypoxia are negative prognostic markers in newly diagnosed patients with gioblastoma, and these important physiologic markers can be measured safely and reliably using MRI and 18F-FMISO PET. Clin Cancer Res; 22(20); 5079-86. ©2016 AACR.

Performance of Positron Emission Tomography and Positron Emission Tomography/Computed Tomography Using Fluorine-18-Fluorodeoxyglucose for the Diagnosis, Staging, and Recurrence Assessment of Bone Sarcoma: A Systematic Review and Meta-Analysis.

To investigate the performance of fluorine-18-fluorodeoxyglucose (F-FDG) positron emission tomography (PET) and PET/computed tomography (CT) in the diagnosis, staging, restaging, and recurrence surveillance of bone sarcoma by systematically reviewing and meta-analyzing the published literature.To retrieve eligible studies, we searched the MEDLINE, Embase, and the Cochrane Central library databases using combinations of following Keywords: "positron emission tomography" or "PET," and "bone tumor" or "bone sarcoma" or "sarcoma." Bibliographies from relevant articles were also screened manually. Data were extracted and the pooled sensitivity, specificity, and diagnostic odds ratio (DOR), on an examination-based or lesion-based level, were calculated to appraise the diagnostic accuracy of F-FDG PET and PET/CT. All statistical analyses were performed using Meta-Disc 1.4.Forty-two trials were eligible. The pooled sensitivity and specificity of PET/CT to differentiate primary bone sarcomas from benign lesions were 96% (95% confidence interval [CI], 93-98) and 79% (95% CI, 63-90), respectively. For detecting recurrence, the pooled results on an examination-based level were sensitivity 92% (95% CI, 85-97), specificity 93% (95% CI, 88-96), positive likelihood ratio (PLR) 10.26 (95% CI, 5.99-17.60), and negative likelihood ratio (NLR) 0.11 (95% CI, 0.05-0.22). For detecting distant metastasis, the pooled results on a lesion-based level were sensitivity 90% (95% CI, 86-93), specificity 85% (95% CI, 81-87), PLR 5.16 (95% CI, 2.37-11.25), and NLR 0.15 (95% CI, 0.11-0.20). The accuracies of PET/CT for detecting local recurrence, lung metastasis, and bone metastasis were satisfactory. Pooled outcome estimates of F-FDG PET were less complete compared with those of PET/CT.F-FDG PET and PET/CT showed a high sensitivity for diagnosing primary bone sarcoma. Moreover, PET/CT demonstrated excellent accuracy for the staging, restaging, and recurrence surveillance of bone sarcoma. However, to avoid misdiagnosis, pathological examination or long-term follow-up should be carried out for F-FDG-avid lesions in patients with suspected bone sarcoma.