Sensitivity Of Positron Emission Tomography Research Articles

Diagnostic Positron Emission Tomography Imaging with Zirconium-89 Desferrioxamine B Squaramide: From Bench to Bedside.

ConspectusMolecular imaging with antibodies radiolabeled with positron-emitting radionuclides combines the affinity and selectivity of antibodies with the sensitivity of Positron Emission Tomography (PET). PET imaging allows the visualization and quantification of the biodistribution of the injected radiolabeled antibody, which can be used to characterize specific biological interactions in individual patients. This characterization can provide information about the engagement of the antibody with a molecular target such as receptors present in elevated levels in tumors as well as providing insight into the distribution and clearance of the antibody. Potential applications of clinical PET with radiolabeled antibodies include identifying patients for targeted therapies, characterization of heterogeneous disease, and monitoring treatment response.Antibodies often take several days to clear from the blood pool and localize in tumors, so PET imaging with radiolabeled antibodies requires the use of a radionuclide with a similar radioactive half-life. Zirconium-89 is a positron-emitting radionuclide that has a radioactive half-life of 78 h and relatively low positron emission energy that is well suited to radiolabeling antibodies. It is essential that the zirconium-89 radionuclide be attached to the antibody through chemistry that provides an agent that is stable in vivo with respect to the dissociation of the radionuclide without compromising the biological activity of the antibody.This Account focuses on our research using a simple derivative of the bacterial siderophore desferrioxamine (DFO) with a squaramide ester functional group, DFO-squaramide (DFOSq), to link the chelator to antibodies. In our work, we produce conjugates with an average ∼4 chelators per antibody, and this does not compromise the binding of the antibody to the target. The resulting antibody conjugates of DFOSq are stable and can be easily radiolabeled with zirconium-89 in high radiochemical yields and purity. Automated methods for the radiolabeling of DFOSq-antibody conjugates have been developed to support multicenter clinical trials. Evaluation of several DFOSq conjugates with antibodies and low molecular weight targeting agents in tumor mouse models gave PET images with high tumor uptake and low background. The promising preclinical results supported the translation of this chemistry to human clinical trials using two different radiolabeled antibodies. The potential clinical impact of these ongoing clinical trials is discussed.The use of DFOSq to radiolabel relatively low molecular weight targeting molecules, peptides, and peptide mimetics is also presented. Low molecular weight molecules typically clear the blood pool and accumulate in target tissue more rapidly than antibodies, so they are usually radiolabeled with positron-emitting radionuclides with shorter radioactive half-lives such as fluorine-18 (t1/2 ∼ 110 min) or gallium-68 (t1/2 ∼ 68 min). Radiolabeling peptides and peptide mimetics with zirconium-89, with its longer radioactive half-life (t1/2 = 78 h), could facilitate the centralized manufacture and distribution of radiolabeled tracers. In addition, the ability to image patients at later time points with zirconium-89 based agents (e.g. 4-24 h after injection) may also allow the delineation of small or low-uptake disease sites as the delayed imaging results in increased clearance of the tracer from nontarget tissue and lower background signal.

Prevalence of metastases outside the liver and abdominal lymph nodes on 68Ga-DOTATOC-PET/CT in patients with small intestinal and pancreatic neuroendocrine tumours.

Metastases outside the liver and abdominal/retroperitoneal lymph nodes are nowadays detected frequently in patients with neuroendocrine tumours (NETs), owing to the high sensitivity of positron emission tomography (PET) with Gallium-68-DOTA-somatostatin analogues (68Ga-SSA) and concomitant diagnostic computed tomography (CT). Our aim was to determine the prevalence of extra-abdominal metastases on 68Ga-DOTATOC-PET/CT in a cohort of patients with small intestinal (Si-NET) and pancreatic NET (Pan-NET), as well as that of pancreatic metastasis in patients with Si-NET. Among 2090 patients examined by 68Ga-DOTATOC-PET/CT at two tertiary referral centres, a total of 1177 patients with a history of Si- or Pan-NET, were identified. The most recent 68Ga-DOTATOC-PET/CT report for each patient was reviewed, and the location and number of metastases of interest were recorded. Lesions outside the liver and abdominal nodes were found in 26% of patients (n = 310/1177), of whom 21.5% (255/1177) were diagnosed with Si-NET and 4.5% (55/1177) Pan-NET. Bone metastases were found in 18.4% (215/1177), metastases to Virchow's lymph node in 7.1% (83/1177), and lung/pleura in 4.8% (56/1177). In the subset of 255 Si-NET patients, 5.4% (41/255) manifested lesions in the pancreas, 1.5% in the breast (18/255), 1.3% in the heart (15/255) and 1% in the orbita (12/255). In Si-NET patients, the Ki-67 proliferation index was higher in those with ≥2 metastatic sites of interest, than with 1 metastatic site, (p <0.001). Overall, extra-abdominal or pancreatic metastases were more often found in patients with Si-NET (34%) than in those with Pan-NET (13%) (p <0.001). Bone metastases were 2.6 times more frequent in patients with Si-NET compared to Pan-NET patients (p <0.001). Lesions to the breast and orbita were encountered in almost only Si-NET patients. In conclusion, lesions outside the liver and abdominal nodes were detected in as many as 26% of the patients, with different prevalence and metastatic patterns in patients with Si-NET compared to Pan-NET. The impact of such metastases on overall survival and clinical decision-making needs further evaluation.

The Role of Magnetic Resonance Spectroscopy, Magnetic Resonance Perfusion and Positron Emission Tomography-Computed Tomography in Post-Radiotherapy Evaluation of Gliomas to Detect Recurrence

Abstract Background and Aim: In this article, the findings of magnetic resonance spectroscopy (MRS), magnetic resonance (MR) perfusion, and positron emission tomography (PET) will be compared and finally correlated with the histopathological examination in all patients having positive imaging findings. The sensitivity and specificity of MRS, MR perfusion, and PET in diagnosing residual/recurrent glioma would be estimated using the histopathological diagnosis as a gold standard. Materials and Methods: Twenty-nine cases of intracranial glioma that had undergone surgery, followed by adjuvant radiotherapy were enrolled in the study. All 29 patients underwent MRS, MR perfusion, and fluorodeoxyglucose (FDG) PET. Results: The sensitivity of MRS to detect recurrence was found to be 83.3% and specificity was 100%. The positive predictive value (PPV) and negative predictive value (NPV) were 100% and 33.3%, respectively. The diagnostic accuracy of MRS was found to be 84.6%. The sensitivity and specificity of MR perfusion to detect recurrence were 91.7% and 100%, respectively. The diagnostic accuracy of MR perfusion is 92.3%. The NPV of MR perfusion was found to be 50%. The sensitivity of PET scans to detect recurrence was 83.3% and specificity was 100%. The PPV of PET was 100% and the NPV was 33.3%. The diagnostic accuracy of the PET scan was found to be 84.6%. Conclusions: Our study shows that all three modalities are useful, however, MR perfusion study is better than MRS and FDG PET in detecting recurrence. MR contrast with perfusion and spectroscopy and FDG PET scan should be included in the protocol for radiotherapy-treated gliomas to differentiate between radiation necrosis, postradiotherapy gliosis, and recurrent/residual tumor.

Expanding a peptide-covalent probe hybrid for PET imaging of S. aureus driven focal infections

BackgroundThe urgent demand for innovative theranostic strategies to combat bacterial resistance to antibiotics is evident, with substantial implications for global health. Rapid diagnosis of life-threatening infections can expedite treatment, improving patient outcomes. Leveraging diagnostic modalities i.e., positron emission tomography (PET) and single photon emission computed tomography (SPECT) for detecting focal infections has yielded promising results. Augmenting the sensitivity of current PET and SPECT tracers could enable effective imaging of pathogenic bacteria, including drug-resistant strains.UBI (29–41), an antimicrobial peptide (AMP) fragment recognizes the S. aureus membrane through electrostatic binding. Radiolabeled UBI (29–41) is a promising SPECT and PET-based tracer for detecting focal infections. 2-APBA (2-acetyl-phenyl-boronic acid), a non-natural amino acid, specifically targets lysyl-phosphatidyl-glycerol (lysyl-PG) on the S. aureus membranes, particularly in AMP-resistant strains. We propose that combining UBI with 2-APBA could enhance the diagnostic potential of radiolabeled UBI.ResultsPresent work aimed to compare the diagnostic potential of two radiolabeled peptides, namely UBI (29–41) and 2-APBA modified UBI (29–41), referred to as UBI and UBI-APBA. APBA modification imparted antibacterial activity to the initially non-bactericidal UBI against S. aureus by inducing a loss of membrane potential. The antibacterial activity demonstrated by UBI-APBA can be ascribed to the synergistic interaction of both UBI and UBI-APBA on the bacterial membrane. To enable PET imaging, we attached the chelator 1,4,7-triazacyclononane 1-glutaric acid 4,7-acetic acid (NODAGA) to the peptides for complexation with the positron emitter Gallium-68 (68Ga). Both NODAGA conjugates were radiolabeled with 68Ga with high radiochemical purity. The resultant 68Ga complexes were stable in phosphate-buffered saline and human serum. Uptake of these complexes was observed in S. aureus but not in mice splenocytes, indicating the selective nature of their interaction. Additionally, the APBA conjugate exhibited superior uptake in S. aureus while preserving the selectivity of the parent peptide. Furthermore, [68Ga]Ga-UBI-APBA demonstrated accumulation at the site of infection in rats, with an improved target-to-non-target ratio, as evidenced by ex-vivo biodistribution and PET imaging.ConclusionsOur findings suggest that linking UBI, as well as AMPs in general, with APBA shows promise as a strategy to augment the theranostic potential of these molecules.

Diagnostic performance of 18F‑DCFPyL PET vs. 68Ga‑PSMA PET/CT in patients with suspected prostate cancer: A systemic review and meta‑analysis.

In this systematic review and meta-analysis, the diagnostic performance of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/CT was compared with that of 18F-DCFPyL PET for patients with suspected prostate cancer (PCa). Up to September 2023, the PubMed, Embase and Web of Science databases were thoroughly searched for relevant papers. Studies examining the diagnostic performance of 18F-DCFPyL PET and 68Ga-PSMA PET/CT in patients with suspected PCa were included in the present review. The Quality Assessment of Diagnostic Performance Studies-2 tool was used to rate the diagnostic performance of each study. The diagnostic performance of 18F-DCFPyL PET and 68Ga-PSMA PET/CT for primary PCa was examined by 13 studies included, comprising 1,178 patients. The pooled sensitivity and specificity of 18F-DCFPyL PET were 0.92 (95% CI, 0.85-0.96) and 0.59 (95% CI, 0.08-0.96), respectively. For 68Ga-PSMA PET/CT, the pooled sensitivity and specificity were 0.96 (95% CI, 0.88-0.99) and 0.71 (95% CI, 0.57-0.82), respectively. 18F-DCFPyL PET and 68Ga-PSMA PET/CT both had an area under the receiver operating characteristic curve of 0.92 (95% CI, 0.89-0.94). In addition, the Fagan nomogram revealed that the post-test probabilities for 18F-DCFPyL PET and 68Ga-PSMA PET/CT could rise to 69 and 77% when the pre-test probability was set at 50%. In conclusion, a comparable diagnostic performance for patients with suspected PCa was determined for 18F-DCFPyL PET and 68Ga-PSMA PET/CT. However, it is crucial to keep in mind that the findings of the present meta-analysis come from investigations with modest sample sizes. Therefore, more extensive research is required to obtain more solid data.

The SNR of time-of-flight positron emission tomography data for joint reconstruction of the activity and attenuation images

Objective. Measurement of the time-of-flight (TOF) difference of each coincident pair of photons increases the effective sensitivity of positron emission tomography (PET). Many authors have analyzed the benefit of TOF for quantification and hot spot detection in the reconstructed activity images. However, TOF not only improves the effective sensitivity, it also enables the joint reconstruction of the tracer concentration and attenuation images. This can be used to correct for errors in CT- or MR-derived attenuation maps, or to apply attenuation correction without the help of a second modality. This paper presents an analysis of the effect of TOF on the variance of the jointly reconstructed attenuation and (attenuation corrected) tracer concentration images. Approach. The analysis is performed for PET systems that have a distribution of possibly non-Gaussian TOF-kernels, and includes the conventional Gaussian TOF-kernel as a special case. Non-Gaussian TOF-kernels are often observed in novel detector designs, which make use of two (or more) different mechanisms to convert the incoming 511 keV photon to optical photons. The analytical result is validated with a simple 2D simulation. Main results. We show that if two different TOF-kernels are equivalent for image reconstruction with known attenuation, then they are also equivalent for joint reconstruction of the activity and the attenuation images. The variance increase in the activity, caused by also jointly reconstructing the attenuation image, vanishes when the TOF-resolution approaches perfection. Significance. These results are of interest for PET detector development and for the development of stand-alone PET systems.

Rationale and design of the RAPID-WATER-FLOW trial: Radiolabeled perfusion to identify coronary artery disease using water to evaluate responses of myocardial FLOW

ObjectivesThe objective of this study was to determine the diagnostic performance of 15O-water positron emission tomography (PET) myocardial perfusion imaging to detect coronary artery disease (CAD) using the truth-standard of invasive coronary angiography (ICA) with fractional flow reserve (FFR) or instantaneous wave-Free Ratio (iFR) or coronary computed tomography angiogram (CCTA). Background15O-water has a very high first-pass extraction that allows accurate quantification of myocardial blood flow and detection of flow-limiting CAD. However, the need for an on-site cyclotron and lack of automated production at the point of care and relatively complex image analysis protocol has limited its clinical use to date. MethodsThe RAPID WATER FLOW study is an open-label, multicenter, prospective investigation of the accuracy of 15O-water PET to detect obstructive angiographic and physiologically significant stenosis in patients with suspected CAD. The study will include the use of an automated system for producing, dosing, and injecting 15O-water and enrolling approximately 215 individuals with suspected CAD at approximately 10 study sites in North America and Europe. The primary endpoint of the study is the diagnostic sensitivity and specificity of the 15O-water PET study using the truth-standard of ICA with FFR or iFR to determine flow-limiting stenosis, or CCTA to rule out CAD and incorporating a quantitative analytic platform developed for the 15O-water PET acquisitions. Sensitivity and specificity are to be considered positive if the lower bound of the 95% confidence interval is superior to the threshold of 60% for both, consistent with prior registration studies.Subgroup analyses include assessments of diagnostic sensitivity, specificity, and accuracy in female, obese, and diabetic individuals, as well as in those with multivessel disease. All enrolled individuals will be followed for adverse and serious adverse events for up to 32 hours after the index PET scan.The study will have >90% power (one-sided test, α = 0.025) to test the hypothesis that sensitivity and specificity of 15O-water PET are both >60%. ConclusionsThe RAPID WATER FLOW study is a prospective, multicenter study to determine the diagnostic sensitivity and specificity of 15O-water PET as compared to ICA with FFR/iFR or CCTA. This study will introduce several novel aspects to imaging registration studies, including a more relevant truth standard incorporating invasive physiologic indexes, coronary CTA to qualify normal individuals for eligibility, and a more quantitative approach to image analysis than has been done in prior pivotal studies. Clinical trial registration informationClinical-Trials.gov (#NCT05134012).

Flurpiridaz F-18 PET Myocardial Perfusion Imaging in Patients With Suspected Coronary Artery Disease

BackgroundFlurpiridaz F-18 (flurpiridaz) is a novel positron emission tomography (PET) myocardial perfusion imaging tracer. ObjectivesThe purpose of this study was to further assess the diagnostic efficacy and safety of flurpiridaz for the detection and evaluation of coronary artery disease (CAD) defined as ≥50% stenosis by quantitative invasive coronary angiography (ICA). MethodsIn this second phase 3 prospective multicenter clinical study, 730 patients with suspected CAD from 48 clinical sites in the United States, Canada, and Europe were enrolled. Patients underwent 1-day rest/stress flurpiridaz PET and 1- or 2-day rest-stress Tc-99m–labeled single photon emission computed tomography (SPECT) before ICA. PET and SPECT images were read by 3 experts blinded to clinical and ICA data. ResultsA total of 578 patients (age 63.7 ± 9.5 years) were evaluable; 32.5% were women, 52.3% had body mass index ≥30 kg/m2, and 33.6% had diabetes. Flurpiridaz PET met the efficacy endpoints of the study; its sensitivity and specificity were significantly higher than the prespecified threshold value by 2 of the 3 readers. The sensitivity of flurpiridaz PET was higher than SPECT (80.3% vs 68.7%; P = 0.0003) and its specificity was noninferior to SPECT (63.8% vs 61.7%; P = 0.0004). PET area under the receiver-operating characteristic curves were higher than SPECT in the overall population (0.80 vs 0.68; P < 0.001), women, and obese patients (P < 0.001 for both). Flurpiridaz PET was superior to SPECT (P < 0.001) for perfusion defect size/severity evaluation, image quality, diagnostic certainty, and radiation exposure. Flurpiridaz PET was safe and well tolerated. ConclusionsThis second flurpiridaz PET myocardial perfusion imaging trial shows that flurpiridaz has utility as a new tracer for CAD detection, specifically in women and obese patients. (An International Study to Evaluate Diagnostic Efficacy of Flurpiridaz [18F] Injection PET MPI in the Detection of Coronary Artery Disease [CAD]; NCT03354273)

Diagnostic value of 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography imaging in acral melanoma-predominant Asian patients.

Tumor staging is crucial for melanoma, of which acral melanoma is the predominant subtype in Asians. 18F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) and 18F-FDG-PET/computed tomography (18F-FDG-PET/CT) serve as non-invasive imaging tools for tumor staging. However, the literature is scarce on the diagnostic value of PET for acral melanoma. From January 1, 2006, to November 30, 2022, a total of 352 patients were diagnosed with melanoma at our hospital. Of them, 90 were diagnosed with cutaneous melanoma and underwent preoperative PET/CT for staging and sentinel lymph node biopsy or complete lymph node dissection. Staging of PET/CT was confirmed by histopathology or following imaging. The lymph node biopsy, distant metastasis status, and PET/CT imaging results were analyzed. Of all the 90 patients with cutaneous melanoma, 72 of them were diagnosed as acral melanoma(80.0%). Compared with the histopathologic results, the lymph nodes were true-positive, true-negative, false-positive, and false-negative in 12, 54, seven, and 17 cases, respectively. The sensitivity of PET/CT for local lymph nodes was 41.4% (95% confidence interval [CI], 23.5-61.1%), while its specificity was 88.5% (95% CI, 77.8-95.3%). As for the detection of distal metastasis, the PET results were true-positive, true-negative, false-positive, and false-negative in six, 65, 15, and four cases, respectively. The sensitivity of PET for distal metastasis detection was 60.0% (95% CI, 26.2-87.8%), while its specificity was 81.3% (95% CI, 71.0-89.1%). Although non-invasive, PET/CT has relatively low sensitivity in regional lymph node evaluations and fair sensitivity in distal metastasis detection in Asian patients with acral melanoma. Thus, PET/CT may be more useful in patients with clinically palpable nodes or more advanced disease stage.

Development of a four-layer DOI PET detector using long crystals segmented by subsurface laser engraving

Since the spatial resolution and sensitivity of positron emission tomography (PET) scanners can be improved by using scintillation detectors with depth-of-interaction (DOI) capability, an original four-layer DOI detector using a pixelated crystal array has been developed in our group. For DOI identification, reflectors have been inserted between the crystals in each layer with a specific arrangement in order to cause light sharing between the layers of the crystal array. However, the precise fabrication of pixelated crystal arrays was challenging and expensive compared to monolithic arrays. In the current study, a four-layer DOI detector composed of long crystals segmented into four segments by applying subsurface laser engraving (SSLE) was proposed. LuYSiO5 (LYSO) crystals of 1 × 1× 20 mm3 were segmented into four segments in the largest dimension using SSLE. A 6 × 6 crystal array using the segmented crystals was prepared and mounted on a 4 × 4 channel multi-pixel photon counter (MPPC, 2 × 2 mm active area). The performance of the proposed detector was investigated and compared with that of original four-layer DOI detector composed of discrete crystals of 1 × 1× 5 mm3 in terms of the crystal identification, layer separation and energy resolution. The 2D position maps of the detectors were obtained by the Anger-logic calculation, and the crystal responses were clearly separated for both detectors. Average energy resolutions of 10.0% ± 1.0%, and 10.5% ± 0.9% at 511 keV were obtained for the proposed detector, and the original detector composed of the discrete crystals, respectively. The layer separation performance was evaluated using separation ratio, which was the ratio of true counts in a specific irradiated crystal in a layer to the total counts in all four crystals stacked on top of each other. The responses of all four layers were clearly separated with a separation ratio of over 0.89 for the proposed and original detectors, respectively. The performance of the proposed detector was well comparable to the original detector composed of the discrete crystals, while the fabrication of the segmented detector was precise and simple.

Diagnostic accuracy of glioma pseudoprogression identification with positron emission tomography imaging: a systematic review and meta-analysis.

Positron emission tomography (PET) imaging is a promising molecular neuroimaging technique and has been proposed as one of the criteria for glioma management. However, there is some controversy concerning the diagnostic accuracy of PET using different radiotracers to differentiate between glioma pseudoprogression (PsP) and true progression (TPR). The purpose of this meta-analysis was to systematically evaluate the methodological quality and clinical value of original studies for distinguishing PsP from TPR in glioma. The Medline, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov were searched from inception until September 1, 2022. Retrieved clinical studies only investigated the PsP cases but did not include the cases of radiation necrosis or other treatment-related changes. Eligible studies were screened for data extraction and evaluated by 2 independent reviewers using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. A random effects model was used to describe summary receiver operating characteristics. Meta-regression and subgroup analyses were applied to identify any sources of heterogeneity. The meta-analysis included 20 studies, comprising 317 (30.9%) patients with PsP and 708 (69.1%) with TPR. The summary sensitivity and specificity of general PET for identifying PsP were 0.86 [95% confidence interval (CI): 0.77-0.91] and 0.84 (95% CI: 0.79-0.88), respectively. The statistical heterogeneity was explained by sample size, study design, World Health Organization (WHO) grade, gold standard, and radiotracer type. The summary sensitivity and specificity of O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET PET) were 0.80 (95% CI: 0.68-0.88) and 0.81 (95% CI: 0.75-0.85), respectively. The maximum tumor-to-brain ratio (TBRmax) and the mean tumor-to-brain ratio (TBRmean) both showed excellent diagnostic performance in 18F-FET studies, the summary sensitivity was 0.83 (95% CI: 0.72-0.91) and 0.79 (95% CI: 0.65-0.98), respectively, and the specificity was 0.76 (95% CI: 0.68-0.84) and 0.78 (95% CI: 0.64-0.88), respectively. PET imaging is generally accurate in identifying glioma PsP. Considering the credibility of meta-evidence and the practicability of using radiotracer, 18F-FET PET holds the highest clinical value, while TBRmax and TBRmean should be regarded as reliable parameters. PET used with the radiotracers and multiple-parameter combinations of PET with magnetic resonance imaging (MRI) and radiomics analysis have broad research and application prospects, whose diagnostic values for identifying glioma PsP warrant further investigation.

Meningioma grading based on positron emission tomography: A systematic review and meta-analysis

IntroductionMeningiomas are the most common central nervous system tumor in adults. Knowledge of the tumor grade can guide optimal treatment timing and shape personalized follow-up strategies. Positron emission tomography (PET) has been utilized for the metabolic assessment of various intracranial space-occupying lesions. Herewith, we set out to evaluate the diagnostic accuracy of PET for the noninvasive assessment of meningioma's grade. Materials and methodsThe Medline, Scopus and Cochrane databases were systematically searched in March 2022 for studies that evaluated the sensitivity and specificity of PET compared to the gold standard of histological diagnosis in the grading of meningiomas. Summary statistics will be calculated and scatter plots, summary curve from the HSROC model and posterior predictions by empirical Bayes estimates will be presented. ResultsFive studies consisting of 242 patients with a total of 196 low-grade (Grade 1) and 46 high grade (Grade 2/3) meningiomas were included in our analysis. Three of the included studies used 18F-FDG, one study used 18F-FLT and one used(Whiting et al., 2011) 18 F-FET as PET tracers. The pooled sensitivity was 76% (95% CI: 52%–91%) and the pooled specificity was 89% (95% CI: 83%–93%). The diagnostic odds ratio was 27.17 (95% CI: 9.22–80.06), the positive likelihood ratio was 7.18 (95% CI: 4.54–11.34) and the negative likelihood ratio was 0.26 (95% CI: 0.11–0.61). ConclusionPET is a promising and viable option as a noninvasive imaging tool to differentiate the meningioma grades. However, currently it cannot overtake the gold standard of histological grade confirmation. More studies are required for further validation and refinement of this imaging technique and assessment of other radiotracers as well.

Diagnostic performance of 18F-FDG PET or PET/CT for detection of myocarditis.

The purpose of the current study was to evaluatethe diagnostic accuracies of fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) or PET/computed tomography (CT) for diagnosis of myocarditis through and a meta-analysis. The PubMed, Cochrane database, and Embase database were searched from inception through November 30, 2022 for studies evaluating diagnostic performance of 18F-FDG PET or PET/CT for diagnosis of acute myocarditis. Based on data extracted from patient-based analysis, we calculated the pooled sensitivity and specificity with the 95% confidence intervals (CI). Also, we calculated positive and negative likelihood ratios (LR+ and LR-), and constructed summary receiver operating characteristic curves. Across 5 studies (6 results, 264 patients), the pooled sensitivity of 18F-FDG PET or PET/CT was 0.57 (95% CI; 0.26-0.84) and a pooled specificity of 0.89 (95% CI; 0.74-0.96). Likelihood ratio (LR) syntheses gave an overall positive likelihood ratio (LR+) of 5.1 and negative likelihood ratio (LR-) of 0.48. The pooled DOR was 11 (95% CI; 2-47). In meta-regression analysis, no variable was the source of the study heterogeneity. Fluorine-18-FDG PET or PET/CT showed insufficient sensitivityand moderate specificity for diagnosis of myocarditis. These results indicated that cautious application of 18F-FDG PET or PET/CT should be paid for detection of myocarditis.

Radiolabeled Iron Oxide Nanoparticles as Dual Modality Contrast Agents in SPECT/MRI and PET/MRI.

During the last decades, the utilization of imaging modalities such as single photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance imaging (MRI) in every day clinical practice has enabled clinicians to diagnose diseases accurately at early stages. Radiolabeled iron oxide nanoparticles (RIONs) combine their intrinsic magnetic behavior with the extrinsic character of the radionuclide additive, so that they constitute a platform of multifaceted physical properties. Thus, at a practical level, RIONs serve as the physical parent of the so-called dual-modality contrast agents (DMCAs) utilized in SPECT/MRI and PET/MRI applications due to their ability to combine, at real time, the high sensitivity of SPECT or PET together with the high spatial resolution of MRI. This review focuses on the synthesis and in vivo investigation of both biodistribution and imaging efficacy of RIONs as potential SPECT/MRI or PET/MRI DMCAs.

18F]RO‐948 Tau PET Retention and Correlation with Fluid Tau Biomarkers in the Early AD Continuum

AbstractBackgroundTau positron emission tomography (PET) imaging enables the in vivo visualization of tau aggregates occurring during the progression of Alzheimer’s disease (AD). Tau PET imaging is a promising biomarker for clinical diagnosis and tracking of disease progression. However, the sensitivity of tau PET in detecting early tau pathology within the early AD continuum and its association with fluid tau biomarkers remains to be established.MethodForty‐seven cognitively unimpaired individuals from the ALFA+ cohort had [18F]RO‐948 and [18F]flutemetamol PET, T1‐weighted magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), and plasma tau biomarkers available (Table1). CSF amyloid(A) and tau(T) positivity were defined using CSF Aß42/40 ratio and ptau181 measured by the exploratory NeuroToolKit and Elecsys® immunoassays, respectively, according to pre‐established thresholds (Milà‐Alomà et al., 2020). Centiloid (CL) values were obtained from [18F]flutemetamol PET scans using a validated pipeline. [18F]RO‐948 uptake was measured in entorhinal (BraakI/II), limbic (BraakIII/IV), and neocortical (BraakV/VI) regions and normalized to the inferior cerebellum to render SUVR values. Regional positivity thresholds per Braak stage were calculated as the median plus two robust standard deviations. Associations between [18F]RO‐948 SUVRs and fluid tau biomarkers were evaluated using Spearman’s rho correlations. P‐values&lt;0.05 were considered statistically significant. [18F]RO‐948 SUVRs were modeled against CL values using the data‐driven robust LOWESS method.ResultIn BraakI/II, 5 cases were considered to be positive, 3 in BraakIII/IV and 2 in BraakV/VI (see Table2 for thresholds), all of them being A+T+. Significant correlations with fluid biomarkers were observed in all Braak stages (Table3, Figure1). [18F]RO‐948 SUVR in BraakI/II showed a linear trend with CL values and inflection points between 20 and 30 CLs were observed for all Braak stages (Figure2).ConclusionA progressively lower number of [18F]RO‐948 PET‐positive cases were detected for more advanced Braak stages as expected from neuropathological studies. [18F]RO‐948 uptake started increasing around 20‐30 CLs and correlated with wet tau biomarkers in cognitively unimpaired individuals, suggesting that [18F]RO‐948 PET can be more sensitive to initial tau pathology than previously thought. These preliminary findings demonstrate that the ALFA+ cohort is well‐suited to study early pathophysiological alterations in preclinical AD stages.

Functional stress imaging to predict abnormal coronary fractional flow reserve: the PACIFIC 2 study.

AimsThe diagnostic performance of non-invasive imaging in patients with prior coronary artery disease (CAD) has not been tested in prospective head-to-head comparative studies. The aim of this study was to compare the diagnostic performance of qualitative single-photon emission computed tomography (SPECT), quantitative positron emission tomography (PET), and qualitative magnetic resonance imaging (MRI) in patients with a prior myocardial infarction (MI) or percutaneous coronary intervention (PCI).Methods and resultsIn this prospective clinical study, all patients with prior MI and/or PCI and new symptoms of ischaemic CAD underwent 99mTc-tetrofosmin SPECT, [15O]H2O PET, and MRI, followed by invasive coronary angiography with fractional flow reserve (FFR) in all coronary arteries. All modalities were interpreted by core laboratories. Haemodynamically significant CAD was defined by at least one coronary artery with an FFR ≤0.80. Among the 189 enrolled patients, 63% had significant CAD. Sensitivity was 67% (95% confidence interval 58–76%) for SPECT, 81% (72–87%) for PET, and 66% (56–75%) for MRI. Specificity was 61% (48–72%) for SPECT, 65% (53–76%) for PET, and 62% (49–74%) for MRI. Sensitivity of PET was higher than SPECT (P = 0.016) and MRI (P = 0.014), whereas specificity did not differ among the modalities. Diagnostic accuracy for PET (75%, 68–81%) did not statistically differ from SPECT (65%, 58–72%, P = 0.03) and MRI (64%, 57–72%, P = 0.052). Using FFR < 0.75 as a reference, accuracies increased to 69% (SPECT), 79% (PET), and 71% (MRI).ConclusionIn this prospective head-to-head comparative study, SPECT, PET, and MRI did not show a significantly different accuracy for diagnosing FFR defined significant CAD in patients with prior PCI and/or MI. Overall diagnostic performances, however, were discouraging and the additive value of non-invasive imaging in this high-risk population is questionable.

18F-flutemetamol positron emission tomography in cardiac amyloidosis

PurposeBone-tracer scintigraphy has an established role in diagnosis of cardiac amyloidosis (CA) as it detects transthyretin amyloidosis (ATTR). Positron emission tomography (PET) with amyloid tracers has shown high sensitivity for detection of both ATTR and light-chain (AL) CA. We aimed to investigate the accuracy of 18F-flutemetamol in CA. MethodsWe enrolled patients with CA or non-amyloid heart failure (NA-HF), who underwent cardiac 18F-flutemetamol PET/MRI or PET/CT. Myocardial and blood pool standardized tracer uptake values (SUV) were estimated. Late gadolinium enhancement (LGE) and T1 mapping/ extracellular volume (ECV) estimation were performed. ResultsWe included 17 patients (12 with CA, 5 with NA-HF). PET/MRI was conducted in 13 patients, while PET/CT was conducted in 4. LGE was detected in 8 of 9 CA patients. Global relaxation time and ECV were higher in CA (1448 vs. 1326, P = 0.02 and 58.9 vs. 33.7%, P = 0.006, respectively). Positive PET studies were demonstrated in 2 of 12 patients with CA (AL and ATTR). Maximal and mean SUV did not differ between groups (2.21 vs. 1.69, P = 0.18 and 1.73 vs. 1.30, P = 0.13). ConclusionAlthough protein-independent binding is supported by our results, the diagnostic yield of PET was low. We demonstrate here for the first time the low sensitivity of PET for CA.

Diagnostic performance of MRI, SPECT, and PET in detecting renal cell carcinoma: a systematic review and meta-analysis

BackgroundRenal cell carcinoma (RCC) is one of the most common malignancies worldwide. Noninvasive imaging techniques, such as magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET), have been involved in increasing evolution to detect RCC. This meta-analysis aims to compare to compare the performance of MRI, SPECT, and PET in the detection of RCC in humans, and to provide evidence for decision-making in terms of further research and clinical settings.MethodsElectronic databases including PubMed, Web of Science, Embase, and Cochrane Library were systemically searched. The keywords such as “magnetic resonance imaging”, “MRI”, “single-photon emission computed tomography”, “SPECT”, “positron emission tomography”, “PET”, “renal cell carcinoma” were used for the search. Studies concerning MRI, SPECT, and PET for the detection of RCC were included. Pooled sensitivity, specificity, and the area under the summary receiver operating characteristic (SROC) curve (AUC), etc. were calculated.ResultsA total of 44 articles were finally detected for inclusion in this study. The pooled sensitivities of MRI, 18F-FDG PET and 18F-FDG PET/CT were 0.80, 0.83, and 0.89, respectively. Their respective overall specificities were 0.90, 0.86, and 0.88. The pooled sensitivity and specificity of MRI studies at 1.5 T were 0.86 and 0.94, respectively. With respect to prospective PET studies, the pooled sensitivity, specificity and AUC were 0.90, 0.93 and 0.97, respectively. In the detection of primary RCC, PET studies manifested a pooled sensitivity, specificity, and AUC of 0.77, 0.80, and 0.84, respectively. The pooled sensitivity, specificity, and AUC of PET/CT studies in detecting primary RCC were 0.80, 0.85, and 0.89.ConclusionOur study manifests that MRI and PET/CT present better diagnostic value for the detection of RCC in comparison with PET. MRI is superior in the diagnosis of primary RCC.

A Human-derived Dual MRI/PET Reporter Gene System with High Translational Potential for Cell Tracking.

Reporter gene imaging has been extensively used to longitudinally report on whole-body distribution and viability of transplanted engineered cells. Multi-modal cell tracking can provide complementary information on cell fate. Typical multi-modal reporter gene systems often combine clinical and preclinical modalities. A multi-modal reporter gene system for magnetic resonance imaging (MRI) and positron emission tomography (PET), two clinical modalities, would be advantageous by combining the sensitivity of PET with the high-resolution morphology and non-ionizing nature of MRI. We developed and evaluated a dual MRI/PET reporter gene system composed of two human-derived reporter genes that utilize clinical reporter probes for engineered cell detection. As a proof-of-concept, breast cancer cells were engineered to co-express the human organic anion transporter polypeptide 1B3 (OATP1B3) that uptakes the clinical MRI contrast agent gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA), and the human sodium iodide symporter (NIS) which uptakes the PET tracer, [18F] tetrafluoroborate ([18F] TFB). T1-weighted MRI results in mice exhibited significantly higher MRI signals in reporter-gene-engineered mammary fat pad tumors versus contralateral naïve tumors (p < 0.05). No differences in contrast enhancement were observed at 5h after Gd-EOB-DTPA administration using either intravenous or intraperitoneal injection. We also found significantly higher standard uptake values (SUV) in engineered tumors in comparison to the naïve tumors in [18F]TFB PET images (p < 0.001). Intratumoral heterogeneity in signal enhancement was more conspicuous in relatively higher resolution MR images compared to PET images. Our study demonstrates the ability to noninvasively track cells engineered with our human-derived dual MRI/PET reporter system, enabling a more comprehensive evaluation of transplanted cells. Future work is focused on applying this tool to track therapeutic cells, which may one day enable the broader application of cell tracking within the healthcare system.

In Vivo Quantitative Whole-Body Perfusion Imaging Using Radiolabeled Copper(II) Bis(Thiosemicarbazone) Complexes and Positron Emission Tomography (PET).

Traditional quantitative perfusion imaging methods require complex data acquisition and analysis strategies; typically require ancillary arterial blood sampling for measurement of input functions; are limited to single organ or tissue regions in an imaging session; and because of their complexity, are not well suited for routine clinical implementation in a standardized fashion that can be readily repeated across diverse clinical sites. The whole-body perfusion method described in this chapter has the advantages of on-demand radiotracer production; simple tissue pharmacokinetics enabling standardized estimation of perfusion; short-lived radionuclides, facilitating repeat or combination imaging procedures; and scalability to support widespread clinical implementation. This method leverages the unique physiological characteristics of radiolabeled copper(II) bis(thiosemicarbazone) complexes and the detection sensitivity of positron emission tomography (PET) to produce quantitatively accurate whole-body perfusion images. This chapter describes the synthesis of ethylglyoxal bis(thosemicarbazonato)copper(II) labeled with copper-62 ([62Cu]Cu-ETS), its unique physiological characteristics, a simple tracer kinetic model for estimation of perfusion using image-derived input functions, and validation of the method against a reference standard perfusion tracer. A detailed description of the methods is provided to facilitate implementation of the perfusion imaging method in PET imaging facilities.