Frontiers in nuclear medicine (Lausanne, Switzerland)最新文献

A 61-year-old woman with a history of metastatic follicular thyroid carcinoma became radioiodine-refractory following two doses of radioiodine (RAI) therapy (cumulative = 230 mCi). While no RAI-avid lesion was noticed in the last post-ablation whole-body radioiodine scan (WBIS), she reported sternal pain, which was accompanied by rapidly rising thyroglobulin levels. ¹⁸F-FDG and ⁶⁸Ga-DOTA-TATE PET/CT was performed, showing metastatic pulmonary nodules and a lytic sternal lesion with acceptable avidity (i.e. uptake ≥ liver). Following four cycles of peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lu-DOTA-TATE, the thyroglobulin levels dropped significantly, and the sternal pain was partially alleviated. Despite only experiencing grade I thrombocytopenia, the treating physician decided to discontinue PRRT and repeat the diagnostic WBIS. Surprisingly, the scan revealed significantly increased tracer uptake in the sternum. The patient received 200 mCi ¹³¹I, and WBIS showed increased RAI uptake in all pulmonary nodules as well as bone metastases. We report a case of RAI-refractory thyroid carcinoma with a somatostatin-receptor expression that re-differentiated and gained significant RAI uptake capacity after PRRT.

Purpose: We present a probabilistic approach to medical image analysis that requires, and makes use of, explicit prior information provided by a medical expert. Depending on the choice of prior model the method can be used for image enhancement, analysis, and segmentation.

Methods: The methodology is based on a probabilistic approach to medical image analysis, that allows integration of 1) arbitrarily complex prior information (for which realizations can be generated), 2) information about a convolution operator of the imaging system, and 3) information about the noise in the reconstructed image into a posterior probability density. The method was demonstrated on positron emission tomography (PET) images obtained from a phantom and a patient with lung cancer. The likelihood model (multivariate log-normal) and the convolution operator were derived from phantom data. Two examples of prior information were used to show the potential of the method. The extended Metropolis-Hastings algorithm, a Markov chain Monte Carlo method, was used to generate realizations of the posterior distribution of the tracer activity concentration.

Results: A set of realizations from the posterior was used as the base of a quantitative PET image analysis. The mean and variance of activity concentrations were computed, as well as the probability of high tracer uptake and statistics on the size and activity concentration of high uptake regions. For both phantom and in vivo images, the estimated images of mean activity concentrations appeared to have reduced noise levels, and a sharper outline of high activity regions, as compared to the original PET. The estimated variance of activity concentrations was high at the edges of high activity regions.

Conclusions: The methodology provides a probabilistic approach for medical image analysis that explicitly takes into account medical expert knowledge as prior information. The presented first results indicate the potential of the method to improve the detection of small lesions. The methodology allows for a probabilistic measure of the size and activity level of high uptake regions, with possible long-term perspectives for early detection of cancer, as well as treatment, planning, and follow-up.

Infection of native tissues or implanted devices is common, but clinical diagnosis is frequently difficult and currently available noninvasive tests perform poorly. Immunocompromised individuals (for example transplant recipients, or those with cancer) are at increased risk. No imaging test in clinical use can specifically identify infection, or accurately differentiate bacterial from fungal infections. Commonly used [¹⁸F]fluorodeoxyglucose (18FDG) positron emission computed tomography (PET/CT) is sensitive for infection, but limited by poor specificity because increased glucose uptake may also indicate inflammation or malignancy. Furthermore, this tracer provides no indication of the type of infective agent (bacterial, fungal, or parasitic). Imaging tools that directly and specifically target microbial pathogens are highly desirable to improve noninvasive infection diagnosis and localization. A growing field of research is exploring the utility of radiometals and their chelators (siderophores), which are small molecules that bind radiometals and form a stable complex allowing sequestration by microbes. This radiometal-chelator complex can be directed to a specific microbial target in vivo, facilitating anatomical localization by PET or single photon emission computed tomography. Additionally, bifunctional chelators can further conjugate therapeutic molecules (e.g., peptides, antibiotics, antibodies) while still bound to desired radiometals, combining specific imaging with highly targeted antimicrobial therapy. These novel therapeutics may prove a useful complement to the armamentarium in the global fight against antimicrobial resistance. This review will highlight current state of infection imaging diagnostics and their limitations, strategies to develop infection-specific diagnostics, recent advances in radiometal-based chelators for microbial infection imaging, challenges, and future directions to improve targeted diagnostics and/or therapeutics.

IgG4-related disease is a fibrous-inflammatory process belonging to immunomodulation disorders. We report a case of a 57-year-old man with the IgG4-related disease (RD). ⁶⁸Ga-FAPI-04 PET/CT showed more significant uptake in most lesions than in ¹⁸F-FDG PET/CT except for the cervical and mediastinal lymph nodes. Besides, uptake in the submandibular glands were only detected in ⁶⁸Ga-FAPI-04 PET/CT. The biopsy result of the cervical lymph nodes confirmed the diagnosis of IgG4-related disease. After treatment, only slight FDG-avid cervical lymph nodes were observed in the ¹⁸F-FDG PET/CT, while the raised uptake of ⁶⁸Ga-FAPI-04 could be observed in the pancreas and submandibular glands. ⁶⁸Ga-FAPI-04 PET-CT might have promising applications in evaluating IgG4-RD, whether in initial or follow-up imaging during steroid therapy.

Introduction: Alzheimer's disease (AD) is characterized by the misfolding and aggregation of two major proteins: amyloid-beta (Aβ) and tau. Antibody-based PET radioligands are desirable due to their high specificity and affinity; however, antibody uptake in the brain is limited by the blood-brain barrier (BBB). Previously, we demonstrated that antibody transport across the BBB can be facilitated through interaction with the transferrin receptor (TfR), and the bispecific antibody-based PET ligands were capable of detecting Aβ aggregates via ex vivo imaging. Since tau accumulation in the brain is more closely correlated with neuronal death and cognition, we report here our strategies to prepare four F-18-labeled specifically engineered bispecific antibody probes for the selective detection of tau and Aβ aggregates to evaluate their feasibility and specificity, particularly for in vivo PET imaging.

Methods: We first created and evaluated (via both in vitro and ex vivo studies) four specifically engineered bispecific antibodies, by fusion of single-chain variable fragments (scFv) of a TfR antibody with either a full-size IgG antibody of Aβ or tau or with their respective scFv. Using [¹⁸F]SFB as the prosthetic group, all four ¹⁸F-labeled bispecific antibody probes were then prepared by conjugation of antibody and [¹⁸F]SFB in acetonitrile/0.1 M borate buffer solution (final pH ~ 8.5) with an incubation of 20 min at room temperature, followed by purification on a PD MiniTrap G-25 size exclusion gravity column.

Results: Based on both in vitro and ex vivo evaluation, the bispecific antibodies displayed much higher brain concentrations than the unmodified antibody, supporting our subsequent F18-radiolabeling. [¹⁸F]SFB was produced in high yields in 60 min (decay-corrected radiochemical yield (RCY) 46.7 ± 5.4) with radiochemical purities of >95%, confirmed by analytical high performance liquid chromatography (HPLC) and radio-TLC. Conjugation of [¹⁸F]SFB and bispecific antibodies showed a 65%-83% conversion efficiency with radiochemical purities of 95%-99% by radio-TLC.

Conclusions: We successfully labeled four novel and specifically engineered bispecific antibodies with [¹⁸F]SFB under mild conditions with a high RCY and purities. This study provides strategies to create brain-penetrable F-18 radiolabeled antibody probes for the selective detection of tau and Aβ aggregates in the brain of transgenic AD mice via in vivo PET imaging.

Introduction: CZT cameras have enabled the noninvasive quantification of myocardial flow reserve (MFR), an important physiologic measure. This study aimed to compare myocardial perfusion SPECT (MPS) with or without MFR evaluation for the detection of obstructive coronary artery disease (CAD).

Methods: 48 patients with CAD (>50% obstruction) detected at invasive coronary angiography or CT angiography underwent dipyridamole MPS and MFR evaluation within 30 days. A 1-day protocol (rest-stress) was used to quantify MFR. The acquisition of dynamic rest and stress images was initiated simultaneously to 99mTc sestamibi injection (370 and 1,110 MBq, respectively), both lasting for 11 min, followed by 5-min imaging. Pharmacologic stress with dipyridamole (0.56 mg/kg for 4 min) was performed with the patient positioned in the CZT camera. The images were processed and time-activity curves were generated, calculating global and regional MFR in a semiautomatic software. A global or regional MFR <2 was considered abnormal. MPS perfusion images were classified as normal or abnormal. The images were interpreted by experienced physicians blinded to the results of MFR and coronary angiography/CT.

Results: Mean age of the population was 61 ± 9 years, 54.2% female. Twenty patients (41.7%) had single-vessel CAD, 22 (45.8%) 2-vessel CAD and 6 (12.5%), triple-vessel CAD. Among the 82 vessels with obstruction, 48 had perfusion abnormalities in MPS and 60 had reduced MFR, while among the normal vessels, had 54 normal MPS and 52 had preserved MFR. The sensitivity of MFR (69%) was higher than that of MPS (55.2%), without significant changes in specificity (86 vs. 83.7%).

Conclusions: MFR in the CZT camera is more sensitive for the detection of CAD than perfusion abnormalities in MPS, especially in patients with multivessel CAD.

The diagnosis of cardiac sarcoidosis (CS) remains challenging. While only a small fraction of patients with systemic sarcoidosis present with clinically symptomatic CS, cardiac involvement has been associated with adverse outcomes, such as ventricular arrhythmia, heart block, heart failure and sudden cardiac death. Despite the clinical relevance of having an early and accurate diagnosis of CS, there is no gold-standard technique available for the assessment of CS. Non-invasive PET and MR imaging have shown promise in the detection of different histopathological features of CS. More recently, the introduction of hybrid PET-MR scanners has enabled the acquisition of these hallmarks in a single scan, demonstrating higher sensitivity and specificity for CS detection and risk stratification than with either imaging modality alone. This article describes recent developments in hybrid PET-MR imaging for improving the diagnosis of CS and discusses areas of future development that could make cardiac PET-MRI the preferred diagnostic tool for the comprehensive assessment of CS.

COVID-19, caused by the SARS-CoV-2 virus, has become a global pandemic that is still present after more than two years. COVID-19 is mainly known as a respiratory disease that can cause long-term consequences referred to as long COVID. Molecular imaging of SARS-CoV-2 in COVID-19 patients would be a powerful tool for studying the pathological mechanisms and viral load in different organs, providing insights into the disease and the origin of long-term consequences and assessing the effectiveness of potential COVID-19 treatments. Current diagnostic methods used in the clinic do not allow direct imaging of SARS-CoV-2. In this work, a nanobody (NB) - a small, engineered protein derived from alpacas - and an Fc-fused NB which selectively target the SARS-CoV-2 Spike protein were developed as imaging agents for positron emission tomography (PET). We used the tetrazine ligation to ¹⁸F-label the NB under mild conditions once the NBs were successfully modified with trans-cyclooctenes (TCOs). We confirmed binding to the Spike protein by SDS-PAGE. Dynamic PET scans in rats showed excretion through the liver for both constructs. Future work will evaluate in vivo binding to the Spike protein with our radioligands.

Objectives: Bacteraemia is associated with significant morbidity and mortality. [18F]FDG-PET/CT is increasingly used to detect infectious metastatic foci, however there remains international variation in its use. We performed a systematic review assessing the impact of [18F]FDG-PET/CT in adult inpatients with gram-positive and Gram-negative bacteraemia.

Design: The systematic review was performed according to PRISMA guidelines. Studies published between 2009 and December 2021 were searched in MEDLINE, EMBASE and Cochrane clinical trials database. Data extraction and quality assessment was performed using ROBINS-I and GRADE.

Setting: Eligible study designs included randomised-controlled trials, clinically-controlled trials, prospective trials, retrospective trials, case-control studies, and non-controlled studies.

Participants: Studies solely assessing adult inpatients with blood-culture confirmed bacteraemia with one cohort of patients receiving [18F]FDG-PET/CT were included.

Main outcome measures: primary outcomes were mortality, identification of metastatic foci and relapse rate. Studies not examining any of the pre-specified outcomes were excluded.

Results: Ten studies were included, of which five had a non-PET/CT control arm. Overall, there was low quality of evidence that [18F]FDG-PET/CT is associated with reduced mortality, improved identification of metastatic foci and reduced relapse rate. Six studies assessed Staphylococcus aureus bacteraemia (SAB) only; nine studies included Gram-positive bacteraemia only, and one study included data from Gram-negative bacteraemia. Two studies compared outcomes between patients with different types of bacteraemia. Four studies identified a statistically significant difference in mortality in [18F]FDG-PET/CT recipients and controls. Relapse rate was significantly reduced in patients with SAB who received [18F]FDG-PET/CT. Studies identified significantly higher detection of metastatic foci in [18F]FDG-PET/CT recipients compared to controls. [18F]FDG-PET/CT was the first to identify an infectious site in 35.5% to 67.2% of overall foci identified.

Conclusions: Further research is required to establish the role of [18F]FDG-PET/CT in bacteraemia, and its impact on management and mortality.