American journal of nuclear medicine and molecular imaging最新文献

We have previously investigated the biodistribution and therapy effect of a humanized monoclonal antibody targeting free prostate-specific antigen (fPSA) intended for theranostics of hormone-refractory prostate cancer. In the present study, we evaluated the off-target effect and different linear energy transfer (LET) radionuclides without the effect of PSA targeting by using an antibody with the same scaffold as previously used immunoconjugates but with random, non-specific, antigen binding region. This allows us to identify alterations generated by specific targeting and those related to passive bystander effects, such as enhanced permeability and retention (EPR). A control humanized IgG monoclonal antibody (hIgG1) and an isotype control IgG monoclonal antibody were conjugated with the chelator CHX-A"-DTPA. The immunoconjugate was radiolabeled with either Lutetium-177 ([¹⁷⁷Lu]Lu) or Indium-111 ([¹¹¹In]In). A biodistribution study in mice carrying LNCaP xenografts, was performed to evaluate the non-specific uptake of [¹⁷⁷Lu]Lu-hIgG1 in tumors and normal organs. Further, therapy studies of [¹⁷⁷Lu]Lu and [¹¹¹In]In labeled IgG were performed in BALB/c mice carrying LNCaP xenografts. Tumor tissues of treated xenografts and control were sectioned and immunohistochemically stained for Ki67 and PSA. The highest tumor uptake for the [¹⁷⁷Lu]Lu-hIgG1 was seen at 72 hours (7.2±2 %IA/g), when comparing the tumor uptake of the fPSA targeting antibody to the non-specific antibody, the non-specific antibody contributes to half of the tumor uptake at 72 h. The liver uptake was 3.1±0.5 %IA/g at 24 h, 2.8±0.5 %IA/g at 72 h and 1.3±0.6 %IA/g at 120 h in LNCaP xenografts, which was approximately three times lower at 24 h and two times lower at 72 h than for the antibody with preserved targeting. Immunohistochemical labeling showed a reduction of PSA expression and a reduction of Ki67 labeled cells in the [¹¹¹In]In treated LNCaP tumors, compared to vehicle and [¹⁷⁷Lu]Lu treated mice. In conclusion, we found that specific targeting might negatively influence normal organ uptake when targeting secreted antigens. Furthermore, different energy deposition i.e. linear energy transfer of a radionuclide might have diverse effects on receptor expression and cell proliferation in tumors.

The cannabinoid subtype 1 receptor (CB1R) is highly expressed in the central nervous system and abnormalities in regional CB1R density are associated with neurodegenerative disorders. The PET tracer [¹⁸F]FMPEP-d₂ is an inverse CB1R agonist which was shown to be suitable for non-invasive PET imaging. In this work, we reported the fully automated radiosynthesis of [¹⁸F]FMPEP-d₂ on a Synthra RNplus research module. In a total synthesis time of 70 min, [¹⁸F]FMPEP-d₂ was obtained in 2.2 ± 0.1 GBq (n = 3) with excellent radiochemical and chemical purity. Quality control test showed that [¹⁸F]FMPEP-d₂ product meets all the release criteria for clinical patient use.

Stroke is the leading cause of disability worldwide, the second most common cause of dementia and the third leading cause of death. Though the etiology of stroke has been explored extensively, there remains open questions in the scientific and clinical study of stroke. Traditional imaging techniques, such as magnetic resonance imaging and computed tomography, have been applied extensively and remain mainstays in clinical practice. Nevertheless, positron emission tomography has proven to be a powerful molecular imaging tool in exploring the scientific aspects of neurological disease, and stroke remains an area of great interest. This review article examines the role of positron emission tomography in the study of stroke including its contributions to elaborating related pathophysiology and delving into possible clinical applications.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm arising from gastrointestinal tract and can be benign or malignant. Rectal GISTs are rare and have poor prognosis. We here reported an older male who presented with features of distending discomfort in the rectum and pain in the anus due to a large rectal tumor. Physical examinations detected a mass in the rectum without blood staining on the gloved finger. Carcinoembryonic antigen (CEA) was found to be slightly elevated and the prostate-specific antigen level was normal. ¹⁸F-FDG PET/CT showed a soft tissue density mass at the bottom of the pelvic, with an unclear boundary to the surroundings with the significantly increased FDG uptake (SUVmax 17.5). Although a rectal carcinoma was suspected based on the finding of PET/CT and CEA, the histopathological examination confirmed the diagnosis of the malignant GIST of the rectum. The patient was then treated with imatinib and on follow-up regularly. In this case, ¹⁸F-FDG PET/CT shows the advantage of visualizing both primary and metastatic lesions and provides valuable information for the diagnosis, staging, evaluation, and prognosis of GIST.

The most prevalent cause of emergency abdominal surgery is acute appendicitis. Ultrasonography is safe and widely available, although it's operator-dependent and difficult for people with massive bodies. Computed tomography (CT) scans are more accurate than ultrasonography, with a 93 to 98% accuracy rate. The goal of this investigation is to evaluate the diagnostic value of ultrasonography and CT scanning for acute appendicitis. This is a cross-sectional study that was performed on 231 patients with suspected with acute appendicitis. The Alvarado score was initially used to diagnose acute appendicitis. A radiologist performed abdominal ultrasonography on all patients. If the results of the ultrasonography were negative or unclear, a CT scan was performed using oral contrast. Finally, all ultrasonography and CT scan data were reevaluated by an experienced radiologist and compared to the patient's final diagnosis in the case of surgery and pathology results. Comparisons between the two groups were performed. The sensitivity, specificity, and positive and negative predictive value of ultrasonography according to pathology results in patients with low clinical suspicion were 74.9%, 63.4%, 94.3%, and 67.6%, respectively. The sensitivity, specificity, positive and negative predictive value of CT scans based on pathology results were 87.9%, 81.8%, 94.7%, and 79.3%, respectively, in patients with low clinical suspicion. The CT scan results in female patients suspected of appendicitis were completely consistent with the pathology results. The CT scan demonstrated greater specificity and sensitivity in diagnosing acute appendicitis compared to abdominal ultrasonography.

The PI3K/Akt/mTOR pathway is frequently dysregulated in cancer due to its central role in cell growth, survival, and proliferation. Overactivation of the PI3K/Akt/mTOR pathway may occur through varying mechanisms including mutations, gene amplification, and upstream signaling events, ultimately resulting in cancer. Therefore, PI3K/Akt/mTOR pathway has emerged as an attractive target for cancer therapy and imaging. A promising approach to inhibit this pathway involves a simultaneous inhibition of both PI3K and mTOR using a dual inhibitor. Recently, a potent dual PI3K/mTOR inhibitor, 2,4-difluoro-N-(2-methoxy-5-(3-(5-(2-(4-methylpiperazin-1-yl)ethyl)-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-6-yl)pyridin-3-yl)benzenesulfonamide (7), was discovered and demonstrated excellent kinase selectivity IC₅₀ (PI3K/mTOR) = 0.20/21 nM; good cellular growth inhibition IC₅₀ (HCT-116 cell) = 10 nM, modest plasma clearance, and acceptable oral bioavailability. Expanding on this discovery, here we present the synthesis of the carbon-11 labeled imidazo[1,2-a]pyridine derivative 2,4-difluoro-N-(2-methoxy-5-(3-(5-(2-(4-[¹¹C]methylpiperazin-1-yl)ethyl)-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-6-yl)pyridin-3-yl)benzenesulfonamide (N-[¹¹C]7) as a new potential radiotracer for the biomedical imaging technique positron emission tomography (PET) imaging of PI3K/mTOR in cancer. The reference standard 7 and its N-demethylated precursor, 2,4-difluoro-N-(2-methoxy-5-(3-(5-(2-(piperazin-1-yl)ethyl)-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-6-yl)pyridin-3-yl)benzenesulfonamide (11), were synthesized in 7 and 8 steps with 10% and 7% overall chemical yield, respectively. N-[¹¹C]7 was prepared from 11 using [¹¹C]methyl triflate ([¹¹C]CH₃OTf) through N-¹¹C-methylation and isolated by high-performance liquid chromatography (HPLC) and solid-phase extraction (SPE) formulation in 40-50% radiochemical yield decay corrected to end of bombardment (EOB) based on [¹¹C]CO₂. The radiochemical purity was > 99% and the molar activity (A_m) at EOB was in the range of 296-555 GBq/µmol (n = 5).

Erdheim-Chester disease (ECD) is a rare and clinically heterogeneous non-Langerhans cell histiocytosis, and its diagnosis relies on established clinical, radiologic, histopathological criteria. ECD can be evaluated by whole-body preoperative imaging methods. Although ¹⁸F-FDG PET/CT shows negative findings in some splenic benign or borderline lesions, such as splenic inflammatory myofibroblastic tumors and hemangioendotheliomas, it can provide value in differentiating some malignant diseases, such as hemangiosarcoma and metastases. Here, we report the CT, MRI, and ¹⁸F-FDG PET/CT imaging performance of an ECD patient who presented with only spleen involvement. Even though some clinical and radiological descriptions can be found in the literature, ECD reports with only splenic involvement mimicking splenic hemangioma as the first presentation are rare, to the best of our knowledge. Histopathology and molecular analysis of this case confirmed the diagnosis of ECD. Clinicians should pay attention to the possibility of ECD occurrence in the spleen, while negative findings on ¹⁸F-FDG PET/CT of the spleen indicated a low risk for high-grade malignant splenic tumors and metastases.

Molecular imaging can dynamically and quantitatively record the biochemical changes in a systemic view. In this research, SARS-CoV-2 pseudovirus was intramuscularly injected to simulate the vaccination with inactivated virus. New Zealand white rabbits were evaluated with ¹⁸F-FDG PET for inflammation and ⁶⁸Ga-cyc-DX600 PET for ACE2 fluctuation, which were performed before and at 3, 7 and 14 days post injection (d P.I.); furthermore, one rabbit was vaccinated with two cycles with interval of 14 days for a longer period evaluation. Different with the vaccination-induced inflammatory response that was random and individual, ACE2 regulation was systemic and organ-specific: the liver and spleen were of a moderate decrease post injection but rebound at 14 d P.I., while there were a downward trend in heart, testis and bone marrow; besides, similar pattern of ACE2 regulation were recorded after the second injection with a relatively greater volatility. In conclusion, ACE2 PET gave a more comprehensive view on host response post vaccination, hold substantial promise in continuous monitoring of coronavirus vaccine administration and effectiveness.

Background: One of the most useful tools for identifying sleep disturbances is neuroimaging, especially magnetic resonance imaging (MRI). This review research was to look at the role of MRI findings in movement disorders and sleep disturbances.

Methods: This review collects all MRI data on movement disorders and sleep disruptions. Between 2000 and 2022, PubMed and Google Scholar were utilized to find original English publications and reviews. According to the inclusion and exclusion criteria, around 100 publications were included. We only looked at research that explored MRI modality together with movement problems, sleep disorders, and brain area involvement. Most of the information focuses on movement irregularities and sleep interruptions.

Results: Movement disorders such as Parkinson's disease (PD), Huntington's disease (HD), neuromuscular diseases, rapid eye movement (REM) sleep behavior movement disorder (RBD), cerebellar movement disorders, and brainstem movement disorders are assessed using MRI-based neuroimaging techniques. Some of the brain areas were associated with disorders in movement abnormalities and related sleep disturbances. This review found that many people with mobility disorders also have sleep problems. Some brain areas' malfunctions may cause motor and sleep issues.

Conclusion: Neuroimaging helps us understand the sleep difficulties associated with movement disorders by examining the structural and functional implications of movement disorders and sleep disturbances.