Molecular Imaging最新文献

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.

Background: Human papillomavirus- (HPV-) associated oropharyngeal squamous cell carcinomas (OPSCCs) are clinically and pathologically distinct from HPV-negative tumors. Here, we explore whether HPV affects functional biomarkers, including γH2AX, RAD51, and PARP1. Moreover, the role of [¹⁸F]PARPi as a broadly applicable imaging tool for head and neck carcinomas is investigated.

Methods: HPV-positive and HPV-negative cell lines were used to evaluate the γH2AX, RAD51, and PARP1 expression with immunoblotting and immunofluorescence. Effects of external beam ionizing radiation were investigated in vitro, and survival was investigated via colony-formation assay. [¹⁸F]PARPi uptake experiments were performed on HPV-negative and HPV-positive cell lines to quantify PARP1 expression. PARP1 IHC and γH2AX foci were quantified using patient-derived oropharyngeal tumor specimens.

Results: Differences in DNA repair were detected, showing higher RAD51 and γH2AX expression in HPV-positive cell lines. Clonogenic assays confirm HPV-positive cell lines to be significantly more radiosensitive. PARP1 expression levels were similar, irrespective of HPV status. Consequently, [¹⁸F]PARPi uptake assays demonstrated that this tracer is internalized in cell lines independently from their HPV status.

Conclusion: The HPV status, often used clinically to stratify patients, did not affect PARP1 levels, suggesting that PARP imaging can be performed in both HPV-positive and HPV-negative patients. This study confirms that the PET imaging agent [¹⁸F]PARPi could serve as a general clinical tool for oropharyngeal cancer patients.

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.

Molecular imaging holds great promise in the noninvasive monitoring of several diseases with nanoparticles (NPs) being considered an efficient imaging tool for cancer, central nervous system, and heart- or bone-related diseases and for disorders of the mononuclear phagocytic system (MPS). In the present study, we used an iron-based nanoformulation, already established as an MRI/SPECT probe, as well as to load different biomolecules, to investigate its potential for nuclear planar and tomographic imaging of several target tissues following its distribution via different administration routes. Iron-doped hydroxyapatite NPs (FeHA) were radiolabeled with the single photon γ-emitting imaging agent [^99mTc]TcMDP. Administration of the radioactive NPs was performed via the following four delivery methods: (1) standard intravenous (iv) tail vein, (2) iv retro-orbital injection, (3) intratracheal (it) instillation, and (4) intrarectal installation (pr). Real-time, live, fast dynamic screening studies were performed on a dedicated bench top, mouse-sized, planar SPECT system from t = 0 to 1 hour postinjection (p.i.), and consequently, tomographic SPECT/CT imaging was performed, for up to 24 hours p.i. The administration routes that have been studied provide a wide range of possible target tissues, for various diseases. Studies can be optimized following this workflow, as it is possible to quickly assess more parameters in a small number of animals (injection route, dosage, and fasting conditions). Thus, such an imaging protocol combines the strengths of both dynamic planar and tomographic imaging, and by using iron-based NPs of high biocompatibility along with the appropriate administration route, a potential diagnostic or therapeutic effect could be attained.

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.

Background: Molecular-MRI is a promising imaging modality for the assessment of abdominal aortic aneurysms (AAAs). Interleukin-1β (IL-1β) represents a new therapeutic tool for AAA-treatment, since pro-inflammatory cytokines are key-mediators of inflammation. This study investigates the potential of molecular-MRI to evaluate therapeutic effects of an anti-IL-1β-therapy on AAA-formation in a mouse-model.

Methods: Osmotic-minipumps were implanted in apolipoprotein-deficient-mice (N = 27). One group (Ang-II+01BSUR group, n = 9) was infused with angiotensin-II (Ang-II) for 4 weeks and received an anti-murine IL-1β-antibody (01BSUR) 3 times. One group (Ang-II-group, n = 9) was infused with Ang-II for 4 weeks but received no treatment. Control-group (n = 9) was infused with saline and received no treatment. MR-imaging was performed using an elastin-specific gadolinium-based-probe (0.2 mmol/kg).

Results: Mice of the Ang-II+01BSUR-group showed a lower aortic-diameter compared to mice of the Ang-II-group and control mice (p < 0.05). Using the elastin-specific-probe, a significant decrease in elastin-destruction was observed in mice of the Ang-II+01BSUR-group. In vivo MR-measurements correlated well with histopathology (y = 0.34x-13.81, R² = 0.84, p < 0.05), ICP-MS (y = 0.02x+2.39; R² = 0.81, p < 0.05) and LA-ICP-MS. Immunofluorescence and western-blotting confirmed a reduced IL-1β-expression.

Conclusions: Molecular-MRI enables the early visualization and quantification of the anti-inflammatory-effects of an IL-1β-inhibitor in a mouse-model of AAAs. Responders and non-responders could be identified early after the initiation of the therapy using molecular-MRI.

The growth hormone secretagogue receptor 1a (GHSR), also called the ghrelin receptor, is a G protein-coupled receptor known to play an important metabolic role in the regulation of various physiological processes, including energy expenditure, growth hormone secretion, and cell proliferation. This receptor has been implicated in numerous health issues including obesity, gastrointestinal disorders, type II diabetes, and regulation of body weight in patients with Prader-Willi syndrome, and there has been growing interest in studying its mechanism of behavior to unlock further applications of GHSR-targeted therapeutics. In addition, the GHSR is expressed in various types of cancer including prostate, breast, and testicular cancers, while aberrant expression has been reported in cardiac disease. Targeted molecular imaging of the GHSR could provide insights into its role in biological processes related to these disease states. Over the past decade, imaging probes targeting this receptor have been discovered for the imaging modalities PET, SPECT, and optical imaging. High-affinity analogues of ghrelin, the endogenous ligand for the GHSR, as well as small molecule inhibitors have been developed and evaluated both in vitro and in pre-clinical models. This review provides a comprehensive overview of the molecular imaging agents targeting the GHSR reported to the end of 2019.