Molecular Imaging最新文献

Sphingosine-1-phosphate receptor 1 (S1PR1) plays a crucial role in infectious diseases. Targeting S1PR1 provides protection against pathogens, such as influenza viruses. This study is aimed at investigating S1PR1 in response to bacterial infection by assessing S1PR1 expression in S. aureus-infected mice. A rodent local muscle bacterial infection model was developed by injecting S. aureus to the lower hind limb of Balb/c mice. The changes of S1PR1 expression in response to bacterial infection and blocking treatment were assessed using ex vivo biodistribution and in vivo positron emission tomography (PET) after intravenous injection of an S1PR1-specific radiotracer [¹⁸F]TZ4877. The specificity of [¹⁸F]TZ4877 was assessed using S1PR1-specific antagonist, NIBR-0213, and S1PR1-specific DsiRNA pretreated the animals. Immunohistochemical studies were performed to confirm the increase of S1PR1 expression in response to infection. Ex vivo biodistribution data showed that the uptake of [¹⁸F]TZ4877 was increased 30.6%, 54.3%, 74.3%, and 115.3% in the liver, kidney, pancreas, and thymus of the infected mice, respectively, compared to that in normal control mice, indicating that S1PR1 is involved in the early immune response to bacterial infection. NIBR-0213 or S1PR1-specific DsiRNA pretreatment reduced the tissue uptake of [¹⁸F]TZ4877, suggesting that uptake of [¹⁸F]TZ4877 is specific. Our PET/CT study data also confirmed that infected mice have increased [¹⁸F]TZ4877 uptake in several organs comparing to that in normal control mice. Particularly, compared to control mice, a 39% increase of [¹⁸F]TZ4877 uptake was observed in the infected muscle of S. aureus mice, indicating that S1PR1 expression was directly involved in the inflammatory response to infection. Overall, our study suggested that S1PR1 plays an important role in the early immune response to bacterial infection. The uptake of [¹⁸F]TZ4877 is tightly correlated with the S1R1 expression in response to S. aureus infection. PET with S1PR1-specific radiotracer [¹⁸F]TZ4877 could provide a noninvasive tool for detecting the early S1PR1 immune response to infectious diseases.

Background: Some studies have reported the effectiveness of [¹⁸F]PI-2620 as an effective tau-binding radiotracer; however, few reports have applied semiquantitative analysis to the tracer. Therefore, this study's aim was to perform a semiquantitative analysis of [¹⁸F]PI-2620 in individuals with normal cognition and patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD).

Methods: Twenty-six cognitively normal (CN) subjects, 7 patients with AD, and 36 patients with MCI were enrolled. A dynamic positron emission tomography (PET) scan was performed 30-75 min postinjection. PET and T1-weighted magnetic resonance imaging scans were coregistered. The standardized uptake value ratio (SUVr) was used for semiquantitative analysis. The P-Mod software was applied to create volumes of interest. The ANOVA and post hoc Tukey HSD were used for statistical analysis.

Results: In the AD group, the occipital lobe had a significantly higher mean SUVr (1.46 ± 0.57) than in the CN and MCI groups. Compared with the CN group, the AD group showed significantly higher mean SUVr in the fusiform gyrus (1.06 ± 0.09 vs. 1.49 ± 0.86), inferior temporal (1.07 ± 0.07 vs. 1.46 ± 0.08), parietal lobe, lingual gyrus, and precuneus regions. Similarly, the AD group demonstrated a higher mean SUVr than the MCI group in the precuneus, lingual, inferior temporal, fusiform, supramarginal, orbitofrontal, and superior temporal regions. The remaining observed regions, including the striatum, basal ganglia, thalamus, and white matter, showed a low SUVr across all groups with no statistically significant differences.

Conclusion: A significantly higher mean SUVr of [¹⁸F]PI-2620 was observed in the AD group; a significant area of the brain in the AD group demonstrated tau protein deposit in concordance with Braak Stages III-V, providing useful information to differentiate AD from CN and MCI. Moreover, the low SUVr in the deep striatum and thalamus could be useful for excluding primary tauopathies.

Background: Inducible nitric oxide synthase (iNOS) plays a crucial role in neuroinflammation, especially microglial activity, and may potentially represent a useful biomarker of neuroinflammation. In this study, we carefully defined a strategic plan to develop iNOS-targeted molecular PET imaging using (4'-amino-5',8'-difluoro-1'H-spiro[piperidine-4,2'-quinazolin]-1-yl)(4-fluorophenyl)methanone ([¹⁸F]FBAT) as a tracer in a mouse model of lipopolysaccharide- (LPS-) induced brain inflammation.

Methods: An in vitro model, murine microglial BV2 cell line, was used to assess the uptake of [¹⁸F]FBAT in response to iNOS induction at the cellular level. In vivo whole-body dynamic PET/MR imaging was acquired in LPS-treated (5 mg/kg) and control mice. Standard uptake value (SUV), total volume of distribution (V _t), and area under the curve (AUC) based on the [¹⁸F]FBAT PET signals were determined. The expression of iNOS was confirmed by immunohistochemistry (IHC) of brain tissues.

Results: At the end of synthesis, the yield of [¹⁸F]FBAT was 2.2-3.1% (EOS), radiochemical purity was >99%, and molar radioactivity was 125-137 GBq/μmol. In vitro, [¹⁸F]FBAT rapidly and progressively accumulated in murine microglial BV2 cells exposed to LPS; however, [¹⁸F]FBAT accumulation was inhibited by aminoguanidine, a selective iNOS inhibitor. In vivo biodistribution studies of [¹⁸F]FBAT showed a significant increase in the liver and kidney on LPS-treated mice. At 3 h postinjection of LPS, in vivo, the [¹⁸F]FBAT accumulation ratios at 30 min post intravenous (i.v.) radiotracer injection for the whole brain, cortex, cerebellum, and brainstem were 2.16 ± 0.18, 1.53 ± 0.25, 1.41 ± 0.21, and 1.90 ± 0.12, respectively, compared to those of mice not injected with LPS. The mean area under the curve (AUC_0-30min), total volume of distribution (V _t, mL/cm³), and K _i (influx rate) of [¹⁸F]FBAT were 1.9 ± 0.21- and 1.4 ± 0.22-fold higher in the 3 h LPS group, respectively, than in the control group. In the pharmacokinetic two-compartment model, the whole brain K _i of [¹⁸F]FBAT was significantly higher in mice injected with LPS compared to the control group. Aminoguanidine, selective iNOS inhibitor, pretreatment significantly reduced the AUC_0-30min and V _t values in LPS-induced mice. Quantitative analysis of immunohistochemically stained brain sections confirmed iNOS was preferentially upregulated in the cerebellum and cortex of mice injected with LPS.

Conclusion: An automated robotic method was established for radiosynthesis of [¹⁸F]FBAT, and the preliminary in vitro and in vivo results demonstrated the fe

We investigated the potential use of [¹⁸F]FDG PET as a response biomarker for PI3K pathway targeting therapies in two HER-2-overexpressing cancer models. Methods. CD-1 nude mice were inoculated with HER-2-overexpressing JIMT1 (trastuzumab-resistant) or SKOV3 (trastuzumab-sensitive) human cancer cells. Animals were treated with trastuzumab, everolimus (mTOR inhibitor), PIK90 (PI3K inhibitor), saline, or combination therapy. [¹⁸F]FDG scans were performed at baseline, two, and seven days after the start of the therapy. Tumors were delineated on CT images and relative tumor volumes (RTV) and maximum standardized uptake value (SUV_max) were calculated. Levels of pS6 and pAkt on protein tumor lysates were determined with ELISA. Results. In the SKOV3 xenografts, all treatment schedules resulted in a gradual decrease in RTV and delta SUV_max (ΔSUV_max). For all treatments combined, ΔSUV_max after 2 days was predictive for RTV after 7 days (r = 0.69, p = 0.030). In JIMT1 tumors, monotherapy with everolimus or PIK90 resulted in a decrease in RTV (-30% ± 10% and -20% ± 20%, respectively) and ΔSUV_max (-39% ± 36% and -42% ± 8%, respectively) after 7 days of treatment, but not earlier, while trastuzumab resulted in nonsignificant increases compared to control. Combination therapies resulted in RTV and ΔSUV_max decrease already at day 2, except for trastuzumab+everolimus, where an early flare was observed. For all treatments combined, ΔSUV_max after 2 days was predictive for RTV after 7 days (r = 0.48, p = 0.028), but the correlation could be improved when combination with everolimus (r = 0.59, p = 0.023) or trastuzumab (r = 0.69, p = 0.015) was excluded. Conclusion. Reduction in [¹⁸F]FDG after 2 days correlated with tumor volume changes after 7 days of treatment and confirms the use of [¹⁸F]FDG PET as an early response biomarker. Treatment response can however be underestimated in schedules containing trastuzumab or everolimus due to temporary increased [¹⁸F]FDG uptake secondary to negative feedback loop and crosstalk between different pathways.

Combining standard drugs with low doses of histone deacetylase inhibitors (HDACIs) is a promising strategy to increase the efficacy of chemotherapy. The ability of well-tolerated doses of HDACIs that act as chemosensitizers for platinum-based chemotherapeutics has recently been proven in many types and stages of cancer in vitro and in vivo. Detection of changes in HDAC activity/expression may provide important prognostic and predictive information and influence treatment decision-making. Use of [¹⁸F] FAHA, a HDAC IIa-specific radionuclide, for molecular imaging may enable longitudinal, noninvasive assessment of HDAC activity/expression in metastatic cancer. We evaluated the synergistic anticancer effects of cisplatin and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in xenograft models of nonsmall cell lung cancer (NSCLC) using [¹⁸F] FAHA and [¹⁸F] FDG PET/CT imaging. Cisplatin alone significantly increased [¹⁸F] FAHA accumulation and reduced [¹⁸F] FDG accumulation in H441 and PC14 xenografts; coadministration of cisplatin and SAHA resulted in the opposite effects. Immunochemical staining for acetyl-histone H3 confirmed the PET/CT imaging findings. Moreover, SAHA had a more significant effect on the acetylome in PC14 (EGFR exon 19 deletion mutation) xenografts than H441 (wild-type EGFR and KRAS codon 12 mutant) xenografts. In conclusion, [¹⁸F] FAHA enables quantitative visualization of HDAC activity/expression in vivo, thus, may represent a clinically useful, noninvasive tool for the management of patients who may benefit from synergistic anticancer therapy.

Up to 30% of patients with epilepsy may not respond to antiepileptic drugs. Patients with drug-resistant epilepsy (DRE) should undergo evaluation for seizure onset zone (SOZ) localization to consider surgical treatment. Cases of drug-resistant nonlesional extratemporal lobe epilepsy (ETLE) pose the biggest challenge in localizing the SOZ and require multiple noninvasive diagnostic investigations before planning the intracranial monitoring (ICM) or direct resection. Ictal Single Photon Emission Computed Tomography (i-SPECT) is a unique functional diagnostic tool that assesses the SOZ using the localized hyperperfusion that occurs early in the seizure. Subtraction ictal SPECT coregistered to MRI (SISCOM), statistical ictal SPECT coregistered to MRI (STATISCOM), and PET interictal subtracted ictal SPECT coregistered with MRI (PISCOM) are innovative SPECT methods for the determination of the SOZ. This article comprehensively reviews SPECT and sheds light on its vital role in the presurgical evaluation of the nonlesional extratemporal DRE.

Objective: To evaluate the diagnostic efficacy of MDA-MB-231 triple-negative breast cancer with ¹²⁵I-labeled pHLIP (Var7) by single-photon emission computed tomography/computed tomography (SPECT/CT) imaging.

Methods: The binding fraction of [¹²⁵I]I-pHLIP (Var7) and MDA-MB-231 cells was measured at pH 7.4 and pH 6.0, and tumor-bearing mice were subjected to small-animal SPECT/CT imaging studies.

Results: At pH = 6.0, the binding fractions of [¹²⁵I]I-pHLIP (Var7) and MDA-MB-231 cells at 10 min, 40 min, 1 h, and 2 h were 1.9 ± 0.1%, 3.5 ± 0.1%, 6.3 ± 0.8%, and 6.6 ± 0.3%, respectively. At pH = 7.4, there was no measured binding between [¹²⁵I]I-pHLIP (Var7) and MDA-MB-231 cells. Small-animal SPECT/CT imaging showed clearly visible tumors at 1 and 2 h after injection.

Conclusions: [¹²⁵I]I-pHLIP (Var7) could bind to MDA-MB-231 cells in an acidic environment, and small-animal SPECT/CT imaging showed clear tumors at 1 and 2 h after probe injection.

Background: Although therapeutic advances have led to enhanced survival in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, detection of residual disease remains challenging. Here, we examine two approved anti-HER2 monoclonal antibodies (mAbs), trastuzumab and pertuzumab, as potential candidates for the development of immunoconjugates for fluorescence-guided surgery (FGS).

Methods: mAbs were conjugated to the near-infrared fluorescent (NIRF) dye, IRDye800, and for quantitative in vitro assessment, to the radiometal chelator, desferrioxamine, to enable dual labeling with ⁸⁹Zr. In vitro binding was evaluated in HER2-overexpressing (BT474, SKBR3) and HER2-negative (MCF7) cell lines. BT474 and MCF7 xenografts were used for in vivo and ex vivo fluorescence imaging.

Results: In vitro findings demonstrated HER2-mediated binding for both fluorescent immunoconjugates and were in agreement with radioligand assays using dual-labeled immunoconjugates. In vivo and ex vivo studies showed preferential accumulation of the fluorescently-labeled mAbs in tumors and similar tumor-to-background ratios. In vivo HER2 specificity was confirmed by immunohistochemical staining of resected tumors and normal tissues.

Conclusions: We showed for the first time that fluorescent trastuzumab and pertuzumab immunoconjugates have similar NIRF imaging performance and demonstrated the possibility of performing HER2-targeted FGS with agents that possess distinct epitope specificity.

Introduction: Standard neuroimaging protocols for brain tumors have well-known limitations. The clinical use of additional modalities including amino acid PET (aaPET) and advanced MRI (aMRI) techniques (including DWI, PWI, and MRS) is emerging in response to the need for more accurate detection of brain tumors. In this systematic review of the past 2 years of the literature, we discuss the most recent studies that directly compare or combine aaPET and aMRI for brain tumor imaging.

Methods: A PubMed search was conducted for human studies incorporating both aaPET and aMRI and published between July 2018 and August 2020.

Results: A total of 22 studies were found in the study period. Recent studies of aaPET with DWI showed a superiority of MET, FET, FDOPA, and AMT PET for detecting tumor, predicting recurrence, diagnosing progression, and predicting survival. Combining modalities further improved performance. Comparisons of aaPET with PWI showed mixed results about spatial correlation. However, both modalities were able to detect high-grade tumors, identify tumor recurrence, differentiate recurrence from treatment effects, and predict survival. aaPET performed better on these measures than PWI, but when combined, they had the strongest results. Studies of aaPET with MRS demonstrated that both modalities have diagnostic potential but MET PET and FDOPA PET performed better than MRS. MRS suffered from some data quality issues that limited analysis in two studies, and, in one study that combined modalities, overall performance actually decreased. Four recent studies compared aaPET with emerging MRI approaches (such as CEST imaging, MR fingerprinting, and SISTINA), but the initial results remain inconclusive.

Conclusions: aaPET outperformed the aMRI imaging techniques in most recent studies. DWI and PWI added meaningful complementary data, and the combination of aaPET with aMRI yielded the best results in most studies.

¹⁸F-sodium fluoride (¹⁸F-NaF) positron emission tomography (PET) has emerged as a promising noninvasive imaging tool for the assessment of active calcification processes in coronary artery disease. ¹⁸F-NaF uptake colocalizes to high-risk and ruptured atherosclerotic plaques. Most recently, ¹⁸F-NaF coronary uptake was shown to be a robust and independent predictor of myocardial infarction in patients with advanced coronary artery disease. In this review, we provide an overview of the advances in coronary ¹⁸F-NaF imaging. In particular, we discuss the recently developed and validated motion correction techniques which address heart contractions, tidal breathing, and patient repositioning during the prolonged PET acquisitions. Additionally, we discuss a novel quantification approach-the coronary microcalcification activity (which has been inspired by the widely employed method in oncology total active tumor volume measurement). This new method provides a single number encompassing ¹⁸F-NaF activity within the entire coronary vasculature rather than just information regarding a single area of most intense tracer uptake.