Positron Emission Tomography In Diagnosis Research Articles

The role of cardiac PET in diagnosis and prognosis of patients with ischemia with no obstructive coronary arteries (INOCA)

Chest pain, a common symptom in cardiovascular care, often leads to the investigation of obstructive coronary artery disease (CAD). However, many patients experience chest pain without obstructive CAD, termed INOCA (Ischemia with Non-Obstructive Coronary Arteries) or CMD (Coronary Microvascular Dysfunction). INOCA can be attributed to endothelial dysfunction, vascular smooth muscle dysfunction, or both, affecting about 20–30 % of patients with nonobstructive CAD. The diagnostic approach for INOCA includes both invasive and non-invasive methods, with cardiac PET (Positron Emission Tomography) playing a significant role in risk stratification and management. PET evaluates various parameters like myocardial blood flow under stress and rest, myocardial flow reserve, and myocardial ischemia. Such comprehensive assessment is essential in accurately diagnosing and managing INOCA, considering the complexity of this condition.

Empowering PET: harnessing deep learning for improved clinical insight.

This review aims to take a journey into the transformative impact of artificial intelligence (AI) on positron emission tomography (PET) imaging. To this scope, a broad overview of AI applications in the field of nuclear medicine and a thorough exploration of deep learning (DL) implementations in cancer diagnosis and therapy through PET imaging will be presented. We firstly describe the behind-the-scenes use of AI for image generation, including acquisition (event positioning, noise reduction though time-of-flight estimation and scatter correction), reconstruction (data-driven and model-driven approaches), restoration (supervised and unsupervised methods), and motion correction. Thereafter, we outline the integration of AI into clinical practice through the applications to segmentation, detection and classification, quantification, treatment planning, dosimetry, and radiomics/radiogenomics combined to tumour biological characteristics. Thus, this review seeks to showcase the overarching transformation of the field, ultimately leading to tangible improvements in patient treatment and response assessment. Finally, limitations and ethical considerations of the AI application to PET imaging and future directions of multimodal data mining in this discipline will be briefly discussed, including pressing challenges to the adoption of AI in molecular imaging such as the access to and interoperability of huge amount of data as well as the "black-box" problem, contributing to the ongoing dialogue on the transformative potential of AI in nuclear medicine.Relevance statementAI is rapidly revolutionising the world of medicine, including the fields of radiology and nuclear medicine. In the near future, AI will be used to support healthcare professionals. These advances will lead to improvements in diagnosis, in the assessment of response to treatment, in clinical decision making and in patient management.Key points• Applying AI has the potential to enhance the entire PET imaging pipeline.• AI may support several clinical tasks in both PET diagnosis and prognosis.• Interpreting the relationships between imaging and multiomics data will heavily rely on AI.

13N-ammonia positron emission tomography for diagnosis and monitoring of ischemia without obstructive coronary artery disease

BackgroundIschemia with no obstructive coronary arteries (INOCA), a chronic disorder with a poor prognosis, remains challenging to diagnose. 13N-ammonia positron emission tomography (13NH3 PET), which can quantify microcirculation, is its most reliable detection method. We aimed to investigate the differences in 13NH3 PET findings between INOCA and coronary artery disease (CAD). MethodsOverall, consecutive 433 patients with known or suspected CAD underwent adenosine-stress 13NH3 PET. Based on the European Society of Cardiology guidelines, INOCA was defined as typical angina without coronary stenosis (INOCA n = 45, CAD n = 293, no CAD n = 95). Papillary muscle ischemia (PMI) and global myocardial flow reserve (MFR) were examined as microvascular injuries using 13NH3 PET. ResultsPMI was observed significantly more frequently in patients with INOCA than in those with CAD (40.0% vs. 11.6%, respectively; p = 0.02). Global MFR (1.84 ± 0.54 vs. 2.08 ± 0.66, respectively; p < 0.0001) and reactive hyperemia index were significantly lower in patients with INOCA than in those with CAD. Forty-five major adverse cardiac events (MACE) were recorded in a median follow-up time of 827 days. Kaplan–Meier analysis revealed that the survival rate worsened in patients with INOCA and PMI (log-rank test, p = 0.001). In the Cox proportional hazards model, PMI was an independent predictive factor for MACE (odds ratio, 4.16; 95% confidence interval, 2.13–8.15; p < 0.0001). ConclusionsPMI presence and decreased MFR were 13NH3 PET findings characteristic of INOCA. 13NH3 PET can be used to monitor the treatment course.

The value of FDG combined with PiB PET in the diagnosis of patients with cognitive impairment in a memory clinic.

To analyze the value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with amyloid PET in cognitive impairment diagnosis. A total of 187 patients with dementia or mild cognitive impairment (MCI) who underwent 11 C-Pittsburgh compound B (PiB) and FDG PET scans in a memory clinic were included in the final analysis. Amyloid-positive and amyloid-negative dementia patient groups showed a significant difference in the proportion of individuals presenting temporoparietal cortex (p < 0.001) and posterior cingulate/precuneus cortex (p < 0.001) hypometabolism. The sensitivity and specificity of this hypometabolic pattern for identifying amyloid pathology were 72.61% and 77.97%, respectively, in patients clinically diagnosed with AD and 60.87% and 76.19%, respectively, in patients with MCI. The initial diagnosis was changed in 32.17% of patients with dementia after considering both PiB and FDG results. There was a significant difference in both the proportion of patients showing the hypometabolic pattern and PiB positivity between dementia conversion patients and patients with a stable diagnosis of MCI (p < 0.05). Temporoparietal and posterior cingulate/precuneus cortex hypometabolism on FDG PET suggested amyloid pathology in patients with cognitive impairment and is helpful in diagnostic decision-making and predicting AD dementia conversion from MCI, particularly when combined with amyloid PET.

Cardiac fludeoxyglucose-18 positron emission tomography in genotype-positive arrhythmogenic cardiomyopathy

BackgroundMyocardial inflammation contributes to the pathogenesis of arrhythmogenic cardiomyopathy (ACM), a clinically and genetically heterogenous disorder. Due to phenotypic overlap, some patients with genetic ACM may be evaluated for an underlying inflammatory cardiomyopathy. However, the cardiac fludeoxyglucose (FDG) positron emission tomography (PET) findings in ACM patients have not been elucidated. MethodsAll genotype-positive patients in the Mayo Clinic ACM registry (n = 323) who received a cardiac FDG PET were included in this study. Pertinent data were extracted from the medical record. ResultsCollectively, 12/323 (4%; 67% female) genotype-positive ACM patients received a cardiac PET FDG scan as part of their clinical evaluation (median age at scan 49 ± 13 years). Amongst these patients, pathogenic/likely pathogenic variants were detected in LMNA (n = 7), DSP (n = 3), FLNC (n = 1) and PLN (n = 1). Of note, 6/12 (50%) had abnormal myocardial FDG uptake, including diffuse (entire myocardium) uptake in 2/6 (33%), focal (1–2 segments) uptake in 2/6 (33%) and patchy (3+ segments) in 2/6 (33%). Median myocardial standardized uptake value ratio was 2.1. Interestingly, LMNA-positive patients accounted for 3 out of 6 (50%) positive studies (diffuse uptake in 2 and focal uptake in 1). ConclusionAbnormal myocardial FDG uptake is common in genetic ACM patients undergoing cardiac FDG PET. This study further supports the role of myocardial inflammation in ACM. Further investigation is needed to determine role of FDG PET in diagnosis and management of ACM and investigate the role of inflammation in ACM.

The Role of Cardiac PET in Diagnosis and Prognosis of Ischemic Heart Disease: Optimal Modality Across Different Patient Populations.

Despite single-photon emission computerized tomography (SPECT) being the most used nuclear imaging technique for diagnosis of coronary artery disease (CAD), many now consider positron emission tomography (PET) as a superior modality. This review will focus on the advances of cardiac PET in recent years and its advantages compared to SPECT in diagnosis and prognosis of CAD. PET's higher resolution and enhanced diagnostic accuracy, as well as lower radiation exposure, all help explain the rationale for its wider spread and use. PET also allows for measurement of myocardial blood flow (MBF) and myocardial flow reserve (MFR), which aids in several different clinical scenarios, such as diagnosing multivessel disease or identifying non-responders. PET has also been shown to be useful in diagnosing CAD in various specific populations, such as patients with prior COVID-19 infection, cardiac transplant, and other comorbidities.

Fully Connected Multi-Kernel Convolutional Neural Network Based on Alzheimer's Disease Diagnosis.

There is a shortage of clinicians with sufficient expertise in the diagnosis of Alzheimer's disease (AD), and cerebrospinal fluid biometric collection and positron emission tomography diagnosis are invasive. Therefore, it is of potential significance to obtain high-precision automatic diagnosis results from diffusion tensor imaging (DTI) through deep learning, and simultaneously output feature probability maps to provide clinical auxiliary diagnosis. We proposed a factorization machine combined neural network (FMCNN) model combining a multi-function convolutional neural network (MCNN) with a fully convolutional network (FCN), while accurately diagnosing AD and mild cognitive impairment (MCI); corresponding fiber bundle visualization results are generated to describe their status. First, the DTI data is preprocessed to eliminate the influence of external factors. The fiber bundles of the corpus callosum (CC), cingulum (CG), uncinate fasciculus (UNC), and white matter (WM) were then tracked based on deterministic fiber tracking. Then the streamlines are input into CNN, MCNN, and FMCNN as one-dimensional features for classification, and the models are evaluated by performance evaluation indicators. Finally, the fiber risk probability map is output through FMCNN. After comparing the model performance indicators of CNN, MCNN, and FMCNN, it was found that FMCNN showed the best performance in the indicators of accuracy, specificity, sensitivity, and area under the curve. By inputting the fiber bundles of the 10 regions of interest (UNC_L, UNC_R, UNC, CC, CG, CG+UNC, CG+CC, CC+UNC, CG+CC+UNC, and WM into CNN, MCNN, and FMCNN, respectively), WM shows the highest accuracy in CNN, MCNN, and FMCNN, which are 88.41%, 92.07%, and 96.95%, respectively. The FMCNN proposed here can accurately diagnose AD and MCI, and the generated fiber probability map can represent the risk status of AD and MCI.

Preliminary Evaluation of Iron Oxide Nanoparticles Radiolabeled with 68Ga and 177Lu as Potential Theranostic Agents

Theranostic radioisotope pairs such as Gallium-68 (68Ga) for Positron Emission Tomography (PET) and Lutetium-177 (177Lu) for radioisotopic therapy, in conjunction with nanoparticles (NPs), are an emerging field in the treatment of cancer. The present work aims to demonstrate the ability of condensed colloidal nanocrystal clusters (co-CNCs) comprised of iron oxide nanoparticles, coated with alginic acid (MA) and stabilized by a layer of polyethylene glycol (MAPEG) to be directly radiolabeled with 68Ga and its therapeutic analog 177Lu. 68Ga/177Lu- MA and MAPEG were investigated for their in vitro stability. The biocompatibility of the non-radiolabeled nanoparticles, as well as the cytotoxicity of MA, MAPEG, and [177Lu]Lu-MAPEG were assessed on 4T1 cells. Finally, the ex vivo biodistribution of the 68Ga-labeled NPs as well as [177Lu]Lu-MAPEG was investigated in normal mice. Radiolabeling with both radioisotopes took place via a simple and direct labelling method without further purification. Hemocompatibility was verified for both NPs, while MTT studies demonstrated the non-cytotoxic profile of the nanocarriers and the dose-dependent toxicity for [177Lu]Lu-MAPEG. The radiolabeled nanoparticles mainly accumulated in RES organs. Based on our preliminary results, we conclude that MAPEG could be further investigated as a theranostic agent for PET diagnosis and therapy of cancer.

The risk of increasing tumor malignancy after PET diagnosis

Abstract This manuscript reviews evidences underlying the estimation of risk of malignancy enhancement of advanced aggressive cancers as a result of the gamma radiation emitted by tracers used in PET diagnostics. We conclude that among many cancers, such a phenomenon likely occurs, particularly in tumor cells with an aggressive biology in the advanced stages of their development, e.g. prostate cancer, melanoma and colorectal cancer. Moreover, we surmise based on gathered evidence that fluorine -18 (18F) labeled pharmaceuticals (18F-deoxyglucose and 18F-choline), commonly used in positron emission tomography (PET) can lead to malignancy enhancement of diagnosed cancer, manifesting as accelerated infiltration of the neighboring tissue, accelerated metastasis and/or radio- and chemotherapy resistance. In this review, some suggestions on future studies verifying this concept are also proposed. If our concerns are justified, it might be appropriate in the future to consider this assumption at the stage of deciding whether to undertake PET monitoring in some patients with advanced aggressive cancer.

A Fruitful Decade of Organofluorine Chemistry: New Reagents and Reactions

A Fruitful Decade of Organofluorine Chemistry: New Reagents and Reactions

PET Research in Clinical Oncology

Positron emission tomography (PET) in nuclear medicine is especially used for diagnosis in clinical oncology, and PET/CT examination using 18F-FDG is very useful for staging and therapy evaluation of cancer. The excellent property of PET diagnosis is that the functional information of cells can be evaluated quantitatively, but it also has the problem that its quantitative value fluctuates depending on image reconstruction conditions and body movements/respiratory movements. In this paper, we summarize the PET research that has been conducted so far in clinical oncology, and also introduce our researches for improve the quantitativeness.

Evaluation of 64Cu-Labeled New Anti-EGFR Antibody NCAB001 with Intraperitoneal Injection for Early PET Diagnosis of Pancreatic Cancer in Orthotopic Tumor-Xenografted Mice and Nonhuman Primates.

Objectives: To improve the prognosis of pancreatic cancer, new imaging methods to identify tumor lesions at a size of <1 cm are urgently needed. To approach this clinical issue, we developed a new method to detect small tumor lesions in the pancreas (≥3 mm) by positron emission tomography (PET) using an intraperitoneally (ip)-administered 64Cu-labeled new anti-epidermal growth factor receptor (EGFR) antibody (encoded as NCAB001), called 64Cu-NCAB001 ipPET. Methods: NCAB001 was manufactured under cGMP conditions and labeled with 64Cu. The radiochemical and biological properties of 64Cu-NCAB001 were evaluated. Tumor uptake of an ip-administered 64Cu-NCAB001 in mice with orthotopic pancreatic tumor xPA1-DC xenografts was also evaluated. Pharmacokinetics and radiation dosimetry were examined using PET images acquired after the ip administration of 64Cu-NCAB001 into cynomolgus monkeys with pharmacologic safety monitoring. Results: Radio-chromatography, cell-binding assays, and biodistribution of 64Cu-NCAB001 in mice were identical to those of our previous data with clinically available cetuximab. Small tumor lesions in the pancreas (≥3 mm) of mice could be identified by 64Cu-NCAB001 ipPET. The ip administration of 64Cu-NCAB001 into monkeys was safely conducted using ultrasound imaging. PET images in monkeys showed that ip-administered 64Cu-NCAB001 was distributed throughout the intraperitoneal cavity for up to 6 h and cleared thereafter. Most of the radioactivity was distributed in the liver and the large intestine. The radioactivity around the pancreas became negligible 24 h after administration. The estimated human effective dose was 0.0174 mSv/MBq. Conclusion: Our data support the initiation of clinical trials of 64Cu-NCAB001 ipPET to transfer this promising tool for the early diagnosis of pancreatic cancers.

Utility of positron emission tomography for diagnosis of systemic juvenile idiopathic arthritis with lung involvement.

Utility of positron emission tomography for diagnosis of systemic juvenile idiopathic arthritis with lung involvement.

Efficacy of positron emission tomography in diagnosis of lateral lymph node metastases in patients with rectal Cancer: a retrospective study

BackgroundThe presence of lateral pelvic lymph node (LLN) metastasis is an essential prognostic factor in rectal cancer patients. Thus, preoperative diagnosis of LLN metastasis is clinically important to determine the therapeutic strategy. The aim of this study was to evaluate the efficacy of preoperative positron emission tomography/computed tomography (PET/CT) in the diagnosis of LLN metastasis.MethodsEighty-four patients with rectal cancer who underwent LLN dissection at Osaka University were included in this study. The maximum standardized uptake value (SUVmax) of the primary tumor and LLN were preoperatively calculated using PET/CT. Simultaneously, the short axis of the lymph node was measured using multi-detector row computed tomography (MDCT). The presence of metastases was evaluated by postoperative pathological examination.ResultsOf the 84 patients, LLN metastases developed in the left, right, and both LLN regions in 6, 7, and 2 patients, respectively. The diagnosis of the metastases was predicted with a sensitivity of 82%, specificity of 93%, positive predictive value of 58%, negative predictive value of 98%, false positive value of 7%, and false negative value of 18% when the cutoff value of the LLN SUVmax was set at 1.5. The cutoff value of the short axis set at 7 mm on MDCT was most useful in diagnosing LLN metastases, but SUVmax was even more useful in terms of specificity.ConclusionsThe cutoff value of 1.5 for lymph node SUVmax in PET is a reasonable measure to predict the risk of preoperative LLN metastases in rectal cancer patients.

Synthesis and evaluation of gallium-68-labeled nitroimidazole-based imaging probes for PET diagnosis of tumor hypoxia

In this study, we designed and synthesized four novel 68Ga-radiolabeled compounds ([68Ga]DN-3, [68Ga]DN-4, [68Ga]NN-3, and [68Ga]NN-4) composed of a nitroimidazole and two types of bifunctional chelates (DOTA or NOTA) via several alkyl linkers of different length. Then, we evaluated their properties as hypoxia imaging probes for positron emission tomography (PET) compared with conventional compounds ([68Ga]DN-2 and [68Ga]NN-2). The precursors of 68Ga-radiolabeled compounds were synthesized through a two-step reaction, and then reacted with 68GaCl3 to be 68Ga-radiolabeled compounds. FaDu cells were treated with 68Ga-radiolabeled compounds and then incubated under normoxic (21% O2) or hypoxic (1% O2) conditions. The radioactivity of these cells was measured 2h after incubation. The biodistribution and PET/CT imaging of 68Ga-radiolabeled compounds in FaDu-bearing Balb/c nude mice were evaluated 2h after intravenous injection. The 68Ga-radiolabeled compounds were synthesized with radiochemical purities over 95%. In the in vitro study, the levels of 68Ga-radiolabeled compounds were significantly higher in hypoxic cells than in normoxic cells. In hypoxic cells, the compounds we designed in this study demonstrated higher accumulation than the conventional compounds. In the in vivo biodistribution study, [68Ga]DN-3 exhibited the highest accumulation in tumor. In the in vivo PET/CT imaging study, the tumor tissues of the FaDu-xenografted mice were visualized at 2h after intravenous administration of 68Ga-radiolabeled compounds. Our study suggested that the length of the linkers connecting nitroimidazole to a bifunctional chelate affect PET imaging of hypoxic tumors with 68Ga-radiolabeled compounds.

The Role of Radionuclide Diagnostic Methods in Neuro-Oncology

In recent years, positron emission tomography (PET) with amino acid radiopharmaceuticals has assumed increasing importance in the diagnosis of brain tumors and it has already become an additional method of examination along with magnetic resonance imaging (MRI) in many diagnostic centers. The markers of somatostatin receptors seem to be most promising for the PET diagnosis of meningiomas. PET provides important additional information in the diagnosis of brain changes of unknown origin and more accurate information about tumor boundaries, which is necessary for biopsy, neurosurgery, and radiation therapy. In addition, labeled amino acid PET aids in the assessment of disease prognosis, in the differentiation of continued tumor growth from nonspecific therapeutic pathomorphism of the brain, and in the evaluation of treatment efficiency at an earlier time than is possible with MRI.

Applications of PET in Diagnosis and Prognosis of Leukemia.

As a malignant hematopoietic stem cell disease, leukemia remains life-threatening due to its increasing incidence rate and mortality rate. Therefore, its early diagnosis and treatment play a very important role. In the present work, we systematically reviewed the current applications and future directions of positron emission tomography (PET) in patients with leukemia, especially 18F-FDG PET/CT. As a useful imaging approach, PET significantly contributes to the diagnosis and treatment of different types of leukemia, especially in the evaluation of extramedullary infiltration, monitoring of leukemia relapse, detection of Richter’s transformation (RT), and assessment of the inflammatory activity associated with acute graft versus host disease. Future investigations should be focused on the potential of PET/CT in the prediction of clinical outcomes in patients with leukemia and the utility of novel radiotracers.

Similar T/N ratio between 18F-FBPA diagnostic and BPA therapeutic dosages for boron neutron capture therapy in orthotropic tongue cancer model.

The tumor-to-normal tissue (T/N) boron ratio is determined in a patient prior to boron neutron capture therapy (BNCT) using 4-borono-2-18F-fluoro-L-phenylalanine (18F-FBPA) positron emission tomography (PET). The T/N ratio is used as a reference parameter to calculate BNCT dose and to evaluate treatment effects. The boronophenylalanine (BPA) dosage for BNCT treatment is higher than the 18F-FBPA dosage for PET diagnosis. Therefore, we aimed to determine whether the T/N ratios between diagnosis and treatment were correlated. In this study, SAS tongue cancer cells were used to develop an orthotopic nude mouse model. Micro-PET was performed after the mice were injected a dose of 3.7 ± 0.74MBq of 18F-FBPA via the tail vein. The 18F radioactivity in the tumor, muscle, and heart blood pool was calculated using AMIND software. Organs and blood were collected for boron concentration analysis using inductively coupled plasma-atomic emission spectroscopy after the mice were injected with 400mg/kg BPA at 15, 30, 45, and 60min. Pharmacokinetics of the tumor and muscle from 45 to 60min after 18F-FBPA and BPA injections were slightly increased, whereas that of blood was slightly decreased. Median T/N ratios at 60min after 18F-FBPA and BPA injections were 3.5 and 3.43, respectively. Median value of the T/N ratio between them was 3.49 at 60min. The T/N ratio at 60min after 18F-FBPA injection was similar to that after BPA injection. However, median tumor-to-blood (T/B) boron ratios of 18F-FBPA and BPA at 60min were 1.63 and 3.35, respectively. Median value between them was 1.83 at 60min. In this study, the T/B ratios demonstrate the spread of a distribution between 18F-FBPA and BPA injections. At 60min, the T/N ratio of the 18F-FBPA injection was similar to that of the BPA injection. Boron concentration in normal tissue was almost equal to that in blood. Therefore, the representative T/N ratio could be obtained at 60min after 18F-FBPA injection, and it was used as a reference parameter for calculating accurate radiation dose.

Positron emission tomography for diagnosis of prosthetic valve endocarditis

Positron emission tomography for diagnosis of prosthetic valve endocarditis

Formation of 107Cd radionuclide impurities during 18F production

Cd isotopes (107Cd and 109Cd) are generated from the silver target body during the bombardment of [18O]water in the routine production of 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) for PET (Positron Emission Tomography) diagnosis. Cadmium isotopes contribute significantly to the total activity of generated impurities and, due to being potentially radiotoxic to living organisms, they should be effectively reduced from FDG to prevent accidental injection of even small concentrations into patients. Purification of the final [18F]FDG can be based on a set of columns, fulfilling various functions in the cleaning process. To assess cadmium impurities and the efficiency of the purification process, a low background gamma spectrometry system with high resolution has been applied.Even activity of 3.5 kBq and 290 kBq has been measured on QMA (Sep-Pak Light Accell Plus QMA) columns for 109Cd and 107Cd isotopes, respectively. 107Cd activity in the five column set was higher than that of 109Cd. The rate of 18F production process was about 1 GBq/min, while that of 107Cd and 109Cd radionuclides was about 4.2 kBq/min and 50 Bq/min respectively.The same purification efficiency of both isotopes has been obtained at each step of the process. The production rate of 107Cd and 109Cd radionuclides was insignificant compared to the 18F production rate. Therefore [18F]FDG final product for use in injections before PET diagnostics was efficiently purified from cadmium radionuclide impurities.