Molecular Imaging最新文献

Purpose: Elevated dopamine synthesis capacity is part of the pathophysiology of schizophrenia thought to underlie psychosis. Drugs that reduce this phenomenon could thus be potential treatments for these disorders. In this study, we evaluated the ability of the trace amine-associated receptor 1 (TAAR1) partial agonist ralmitaront to reduce presynaptic dopamine synthesis capacity.

Procedures: Ralmitaront (3 mg/kg, i.p.), a TAAR1 partial agonist, was evaluated using [¹⁸F]DOPA PET for its ability to modulate presynaptic dopamine synthesis capacity in naïve mice as well as mice in an induced hyperdopaminergic state following acute cocaine administration (20 mg/kg, i.p.).

Results: Cocaine treatment on its own did not induce elevated dopamine synthesis capacity when compared to the control group. Pretreatment with ralmitaront significantly reduced dopamine synthesis capacity when given either alone (44%) or in combination with the psychostimulant cocaine (50%) when compared to the control group.

Conclusions: The TAAR1 agonist ralmitaront reduces striatal dopamine synthesis capacity, indexed as Ki^Mod, both in naïve animals and when given prior to acute cocaine. This indicates the potential of TAAR1 agonism to address disorders characterized by striatal hyperdopaminergia.

Background: In rodents, 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) catalyzes the conversion of inactive 11-dehydrocorticosterone to the active hormone corticosterone. Dysregulation of intracellular glucocorticoid action is implicated in metabolic diseases. Assessing 11β-HSD1 enzyme levels in vivo may be key to understanding obesity pathophysiology.

Objective: We used a Zucker Fatty (ZF) rat model and [¹⁸F]AS2471907 PET imaging to determine appropriate kinetic modeling methods and assess changes in 11β-HSD1 levels due to obesity in the liver, white and brown adipose tissue (WAT/BAT), and brain.

Material and methods: To validate [¹⁸F]AS2471907 PET in preclinical models, time-activity curves (TACs) were generated and kinetic modeling was performed with image-derived input functions (IDIFs) extracted from multiple locations. Quantitative estimates of radioligand binding were compared with ex vivo 11β-HSD1 protein expression. Validated quantitative PET kinetic modeling methods were then used to assess differences in 11β-HSD1 between lean and obese ZF rats. Metabolic disease status was confirmed with stable isotopes tracer studies of glucose and fatty acid metabolism.

Results: Obesity is associated with decreased brain 11β-HSD1 levels, measured by [¹⁸F]AS2471907 PET, which correlated with measures of glucose and fatty acid metabolism.

Conclusion: We demonstrate that [¹⁸F]AS2471907 PET can provide useful quantification of 11β-HSD1 levels in a rodent model of obesity.

Immunologic thrombocytopenic purpura (ITP) is a condition that affects four to 18 per 100 000 children every year. In most cases, spontaneous remission occurs, but splenectomy may be proposed. Exploring the site of platelet sequestration can help to better predict potential poor responders to splenectomy, but ¹¹¹In-radiolabeled platelet scintigraphy (IPS) can be difficult to perform in children with very few platelets. A 12-year-old boy suffering from refractory ITP was referred for evaluation of platelet survival and sequestration and consideration of splenectomy. His platelet count consistently remained below 10 000/mm³. An exceptional procedure was set up to use homologous platelets to perform the IPS. Splenectomy was ruled out based on the results of ¹¹¹In-radiolabeled homologous platelet scintigraphy. The attending pediatrician intensified medical treatments, resulting in a significant improvement in platelet count. This increase in platelet levels allowed for ¹¹¹In-radiolabeled autologous platelet scintigraphy, which confirmed the absence of splenic sequestration. This allowed us to reject splenectomy in this child. Homologous IPS could help clinicians to choose splenectomy as a treatment option for ITP in children with a very low platelet count, and its use should be promoted after failed thrombopoietin receptor agonist (TPO-RA) treatment. More systematic studies are needed to confirm the predictive response to splenectomy of homologous IPS.

Introduction and purpose: Radiopharmaceutical therapy (RPT) dosimetry can be challenging to perform due to sparse data measurements and variations in how the time activity curve (TAC) is determined. In this work, a single system of equations was theoretically derived to estimate the TAC.

Methods: A pharmacokinetic (PK) model was developed to estimate patient specific rate constants for a given set of body compartments. The PK model and an optimizer were numerically implemented to determine the rate constants and, using these physiologic data, to generate TACs and time integrated activities (TIAs) for 3 tissue systems from clinical data gathered in 5 patients. A fourth (aggregate) tissue compartment is added using conservation of activity considerations.

Results: Feasibility of the PK model was demonstrated by successfully generating TACs and TIAs for all patients in a manner comparable to existing methods in the literature. The data are compared to smaller sampling regimes. Differences between the 3- and 4-compartment models show that conservation of activity considerations should be part of TAC estimations.

Conclusion: The results here suggest a new paradigm in RPT in using the rate constants so identified as a diagnostic tool and as a vehicle to achieving individualized tumorcidal dose and/or the maximum tolerable dose to normal tissues.

Objective: 2-Deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) is widely used for noninvasive imaging of atherosclerosis. However, knowledge about metabolic processes underlying [¹⁸F]FDG uptake is mostly derived from in vitro cell culture studies, which cannot recapitulate the complexities of the plaque microenvironment. Here, we sought to address this gap by in situ mapping of the activity of selected major dehydrogenases involved in glucose metabolism in atherosclerotic plaques.

Methods: In situ activity of lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G6PD), succinate dehydrogenase (SDH), and isocitrate dehydrogenase (IDH) was assessed in plaques from murine aortic root and brachiocephalic arteries and human carotid arteries. High-resolution 2-deoxy-D-[1,2-³H]glucose ([³H]2-deoxyglucose) autoradiography of murine brachiocephalic plaques was performed.

Results: LDH activity was heterogeneous throughout the plaques with the highest activity in medial smooth muscle cells (SMCs). G6PD activity was mostly confined to the medial layer and to a lesser extent to SMCs along the fibrous cap. SDH and IDH activities were minimal in plaques. Plaque regions with increased [³H]2-deoxyglucose uptake were associated with a modestly higher LDH, but not G6PD, activity.

Conclusions: Our study reveals a novel aspect of the metabolic heterogeneity of the atherosclerotic plaques, enhancing our understanding of the complex immunometabolic biology that underlies [¹⁸F]FDG uptake in atherosclerosis.

Background: Ankylosing spondylitis (AS) is characterized by inflammation and osteoblastic changes in the sacroiliac joint. As a potential imaging method for the early assessment of AS, positron emission tomography (PET) can quantify systemic disease activity, which is conducive to monitoring the progression of disease activity and assisting in evaluating the efficacy of the treatment.

Objective: The study was to evaluate the diagnostic value of aluminium-[¹⁸F]fuoride(Al¹⁸F)-labelled fibroblast activation protein inhibitor (FAPI) PET/computed tomography (CT) in AS and to investigate its ability to assess disease activity during the development of AS.

Material and methods: Twenty AS participants who met the Assessment of SpondyloArthritis international Society criteria and were in an active disease stage were included in this study from May 2022 to April 2023. Sixteen healthy controls were also inrolled. All participants underwent Al¹⁸F-NOTA-FAPI-04 PET/CT imaging after collecting clinical assessment and laboratory results. The correlation between positive joint count (PJC) and systemic joint standard uptake value ratio (SUVR, the mean SUV_max of the 5 highest joints/SUV_max of the uninvolved sacrum) on PET and clinical disease activity assessment and various laboratory tests were analyzed.

Results: A total of 2820 joints were observed in 20 participants (median age 34.5,[21-61]range, 15 men), with a PJC of 1300 (46.7%), and 39 positive uptakes were found in 40 sacroiliac joints (97.5%). PET/CT images revealed FAPI-04 uptake in both sacroiliac joints in 2 participants without radiographic sacroiliitis in the early stages of AS and varying degrees of uptake in the sacroiliac joints and spinal joints in the remaining participants. PJC and SUVR were positively correlated with most clinical assessments and laboratory findings (P < .05), and SUVR of the sacroiliac joint was positively correlated with C-reactive protein (CRP) (mg/L; r = 0.498, P = .026).

Conclusion: Al¹⁸F-NOTA-FAPI-04 PET/CT was highly sensitive to systemic arthritic changes in AS participants and correlated with clinical disease activity and laboratory tests.

Background: Labeled antibodies are excellent imaging agents in oncology to non-invasively visualize cancer-related antigens expression levels. However, tumor tracer uptake (TTU) of specific antibodies in-vivo may be inferior to non-specific IgG in some cases.

Objectives: To explore factors affecting labeled antibody visualization by PD-L1 specific and non-specific imaging of nude mouse tumors.

Methods: TTU was observed in RKO model on Cerenkov luminescence (CL) and near-infrared fluorescence (NIRF) imaging of radionuclide ¹³¹I or NIRF dyes labeled Atezolizumab and IgG. A mixture of NIRF dyes labeled Atezolizumab and ¹³¹I-labeled IgG was injected, and TTU was observed in the RKO and HCT8 model by NIRF/CL dual-modality in-situ imaging. TTU were observed by ¹³¹I-labeled Atezolizumab and IgG in-vitro distribution.

Results: Labeled IgG concentrated more in tumors than Atezolizumab. NIRF/CL imaging in 24 to 168 h showed that TTU gradually decreased over time, which decreased more slowly on CL imaging compared to NIRF imaging. The distribution data in-vitro showed that TTU of ¹³¹I-labeled IgG was higher than that of ¹³¹I-labeled Atezolizumab at any time point.

Conclusion: Non-specific IgG may not be suitable as a control for Atezolizumab in comparing tumor PD-L1 expression in nude mice via labeled antibody optical imaging under certain circumstances.

Objective: To investigate the performance of diffusion-tensor imaging (DTI) and hydrogen proton magnetic resonance spectroscopy (¹H-MRS) parameters in predicting the immunohistochemistry (IHC) biomarkers of glioma.

Methods: Patients with glioma confirmed by pathology from March 2015 to September 2019 were analyzed, the preoperative DTI and ¹H-MRS images were collected, apparent diffusion coefficient (ADC) and fractional anisotropy (FA), in the lesion area were measured, the relative values relative ADC (rADC) and relative FA (rFA) were obtained by the ratio of them in the lesion area to the contralateral normal area. The peak of each metabolite in the lesion area of ¹H-MRS image: N-acetylaspartate (NAA), choline (Cho), and creatine (Cr), and metabolite ratio: NAA/Cho, NAA/(Cho + Cr) were selected and calculated. The preoperative IHC data were collected including CD34, Ki-67, p53, S-100, syn, vimentin, NeuN, Nestin, and glial fibrillary acidic protein.

Results: One predicting parameter of DTI was screened, the rADC of the Ki-67 positive group was lower than that of the negative group. Two parameters of ¹H-MRS were found to have significant reference values for glioma grades, the NAA and Cr decreased as the grade of glioma increased, moreover, Ki-67 Li was negatively correlated with NAA and Cr.

Conclusion: NAA and Cr have potential application value in predicting glioma grades and tumor proliferation activity. Only rADC has predictive value for Ki-67 expression among DTI parameters.

Chimeric antigen receptor (CAR)-T cell-based immunotherapy has emerged as a path-breaking strategy for certain hematological malignancies. Assessment of the response to CAR-T therapy using quantitative imaging techniques such as positron emission tomography/computed tomography (PET/CT) has been broadly investigated. However, the definitive role of PET/CT in CAR-T therapy remains to be established. [¹⁸F]FDG PET/CT has demonstrated high sensitivity and specificity for differentiating patients with a partial and complete response after CAR-T therapy in lymphoma. The early therapeutic response and immune-related adverse effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome can also be detected on [¹⁸F]FDG PET images. In otherwise asymptomatic lymphoma patients with partial response following CAR-T therapy, the only positive findings could be abnormal PET/CT results. In multiple myeloma, a negative [¹⁸F]FDG PET/CT after receiving B-cell maturation antigen-directed CAR-T therapy has been associated with a favorable prognosis. In leukemia, [¹⁸F]FDG PET/CT can detect extramedullary metastases and treatment responses after therapy. Hence, PET/CT is a valuable imaging tool for patients undergoing CAR-T therapy for pretreatment evaluation, monitoring treatment response, assessing safety, and guiding therapeutic strategies. Developing guidelines with standardized cutoff values for various PET parameters and tumor cell-specific tracers may improve the efficacy and safety of CAR-T therapy.

This meeting report summarizes a consultants meeting that was held at International Atomic Energy Agency Headquarters, Vienna, in July 2022 to provide an update on the development of multimodality imaging by combining nuclear medicine imaging agents with other nonradioactive molecular probes and/or biomedical imaging techniques.