Molecular Imaging最新文献

{"title":"Dual-Energy SPECT and the Development of Peptide p5+14 for Imaging Amyloidosis.","authors":"Jonathan S Wall, Stephen J Kennel, Emily B Martin","doi":"10.1177/1536012117708705","DOIUrl":"10.1177/1536012117708705","url":null,"abstract":"<p><p>Amyloidosis is associated with a number of rare diseases and is characterized by the deposition, in abdominothoracic organs and peripheral nerves, of extracellular protein fibrils, which leads to dysfunction and severe morbidity. Effective clinical evaluation and management of patients with systemic amyloidosis are hampered by the lack of a noninvasive, quantitative method for detecting whole-body amyloid load. We have used a battery of assays including dual-energy SPECT imaging and comparative effectiveness studies in support of translation of a synthetic polybasic peptide, p5+14, as a novel radiotracer for visualization of amyloidosis by molecular imaging. These data provide support for a phase 1 positron emission tomography/computed tomography imaging trial of this reagent, labeled with iodine-124, in patients with all forms of systemic amyloidosis.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"16 ","pages":"1536012117708705"},"PeriodicalIF":2.8,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1d/c4/10.1177_1536012117708705.PMC5469514.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35122875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking Brain Cancer Therapy: Tumor Enzyme Activatable Theranostic Nanoparticles.","authors":"Heike E Daldrup-Link","doi":"10.1177/1536012117730950","DOIUrl":"10.1177/1536012117730950","url":null,"abstract":"<p><p>This invited commentary discusses a recent article by Mohanty et al in Molecular Cancer Therapeutics about significant therapeutic efficacies of novel theranostic nanoparticles (TNPs) for the treatment of human brain cancers in mouse models. The TNPs were cleaved by enzymes in the tumor tissue, matrix metalloproteinase (MMP-14), which lead to release of a highly potent therapeutic drug, azademethylcolchicine. Data showed that the TNPs caused selective toxic effects in MMP-14-expressing glioblastoma and not normal brain. In addition, the iron oxide nanoparticle backbone enabled in vivo drug tracking with magnetic resonance imaging (MRI). This commentary discusses previous efforts of MMP-targeted therapeutics as well as opportunities for further refinements of tumor enzyme-activatable TNPs. If successfully translated to clinical applications, the TNPs might hold substantial potential to improving cytotoxic indexes and long-term outcomes of patients with brain cancer compared to standard therapy.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"16 ","pages":"1536012117730950"},"PeriodicalIF":2.8,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2c/0c/10.1177_1536012117730950.PMC5613837.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35426836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging Bone-Cartilage Interactions in Osteoarthritis Using [¹⁸F]-NaF PET-MRI.","authors":"Dragana Savic,&nbsp;Valentina Pedoia,&nbsp;Youngho Seo,&nbsp;Jaewon Yang,&nbsp;Matt Bucknor,&nbsp;Benjamin L Franc,&nbsp;Sharmila Majumdar","doi":"10.1177/1536012116683597","DOIUrl":"https://doi.org/10.1177/1536012116683597","url":null,"abstract":"<p><strong>Purpose: </strong>Simultaneous positron emission tomography-magnetic resonance imaging (PET-MRI) is an emerging technology providing both anatomical and functional images without increasing the scan time. Compared to the traditional PET/computed tomography imaging, it also exposes the patient to significantly less radiation and provides better anatomical images as MRI provides superior soft tissue characterization. Using PET-MRI, we aim to study interactions between cartilage composition and bone function simultaneously, in knee osteoarthritis (OA).</p><p><strong>Procedures: </strong>In this article, bone turnover and remodeling was studied using [¹⁸F]-sodium fluoride (NaF) PET data. Quantitative MR-derived T_1ρ relaxation times characterized the biochemical cartilage degeneration. Sixteen participants with early signs of OA of the knee received intravenous injections of [¹⁸F]-NaF at the onset of PET-MR image acquisition. Regions of interest were identified, and kinetic analysis of dynamic PET data provided the rate of uptake ( K_i) and the normalized uptake (standardized uptake value) of [¹⁸F]-NaF in the bone. Morphological MR images and quantitative voxel-based T_1ρ maps of cartilage were obtained using an atlas-based registration technique to segment cartilage automatically. Voxel-by-voxel statistical parameter mapping was used to investigate the relationship between bone and cartilage.</p><p><strong>Results: </strong>Increases in cartilage T_1ρ, indicating degenerative changes, were associated with increased turnover in the adjoining bone but reduced turnover in the nonadjoining compartments. Associations between pain and increased bone uptake were seen in the absence of morphological lesions in cartilage, but the relationship was reversed in the presence of incident cartilage lesions.</p><p><strong>Conclusion: </strong>This study shows significant cartilage and bone interactions in OA of the knee joint using simultaneous [¹⁸F]-NaF PET-MR, the first in human study. These observations highlight the complex biomechanical and biochemical interactions in the whole knee joint in OA, which potentially could help assess therapeutic targets in treating OA.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"15 ","pages":"1-12"},"PeriodicalIF":2.8,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012116683597","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35122789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Imaging of the Human Pulmonary Vascular Endothelium Using an Adrenomedullin Receptor Ligand.","authors":"François Harel,&nbsp;Xavier Levac,&nbsp;Quang T Nguyen,&nbsp;Myriam Létourneau,&nbsp;Sophie Marcil,&nbsp;Vincent Finnerty,&nbsp;Mariève Cossette,&nbsp;Alain Fournier,&nbsp;Jocelyn Dupuis","doi":"10.2310/7290.2015.00003","DOIUrl":"https://doi.org/10.2310/7290.2015.00003","url":null,"abstract":"<p><p>This phase I study (NCT01539889) evaluated the safety, efficacy, and dosing of PulmoBind for molecular imaging of pulmonary circulation. PulmoBind is a ligand of the adrenomedullin receptor abundantly distributed in lung capillaries. Labeled with ^99mTc, it allows single-photon emission computed tomographic (SPECT) imaging of lung perfusion. In preclinical studies, PulmoBind scans enabled detection of lung perfusion defects and quantification of microcirculatory occlusion caused by pulmonary hypertension. Healthy humans ( N = 20) were included into escalating groups of 5 mCi ( n = 5), 10 mCi ( n = 5), or 15 mCi ( n = 10) ^99mTc-PulmoBind. SPECT imaging was serially performed, and ^99mTc-PulmoBind dosimetric analysis was accomplished. The radiochemical purity of ^99mTc-PulmoBind was greater than 95%. There were no safety concerns at the three dosages studied. Imaging revealed predominant and prolonged lung uptake with a mean peak extraction of 58% ± 7%. PulmoBind was well tolerated, with no clinically significant adverse event related to the study drug. The highest dose of 15 mCi provided a favorable dosimetric profile and excellent imaging. The postural lung perfusion gradient was detectable. ^99mTc-PulmoBind is safe and provides good quality lung perfusion imaging. The safety/efficacy of this agent can be tested in disorders of pulmonary circulation such as pulmonary arterial hypertension.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"14 5","pages":"7290201500003"},"PeriodicalIF":2.8,"publicationDate":"2015-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2310/7290.2015.00003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35121575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monitoring Tumor Targeting and Treatment Effects of IRDye 800CW and GX1-Conjugated Polylactic Acid Nanoparticles Encapsulating Endostar on Glioma by Optical Molecular Imaging.","authors":"Yaqian Li,&nbsp;Yang Du,&nbsp;Xia Liu,&nbsp;Qian Zhang,&nbsp;Lijia Jing,&nbsp;Xiaolong Liang,&nbsp;Chongwei Chi,&nbsp;Zhifei Dai,&nbsp;Jie Tian","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Molecular imaging used in cancer diagnosis and therapeutic response monitoring is important for glioblastoma (GBM) research. Antiangiogenic therapy currently is one of the emerging approaches for GBM treatment. In this study, a multifunctional nanoparticle was fabricated that can facilitate the fluorescence imaging of tumor and deliver a therapeutic agent to the tumor region in vivo and therefore possesses broad application in cancer diagnosis and treatment. This particle was polylactic acid (PLA) nanoparticles encapsulating Endostar, which was further conjugated with GX1 peptide and the near-infrared (NIR) dye IRDye 800CW (IGPNE). We demonstrated noninvasive angiogenesis targeting and therapy of IGPNE on U87MG xenografts in vivo using dual-modality optical molecular imaging including NIR fluorescence molecular imaging (FMI) and bioluminescence imaging (BLI). The NIR FMI results demonstrated that IGPNE had more accumulation to the tumor site compared to free IRDye 800CW. To further evaluate the antitumor treatment efficacy of IGPNE, BLI and immunohistochemistry analysis were performed on tumor-bearing mice. With the aid of molecular imaging, the results confirmed that IGPNE enhanced antitumor treatment efficacy compared to free Endostar. In conclusion, IGPNE realizes real-time imaging of U87MG tumors and improves the antiangiogenic therapeutic efficacy in vivo.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"14 ","pages":"356-65"},"PeriodicalIF":2.8,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34278838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PET Imaging of Steroid Hormone Receptor Expression.","authors":"Louis Allott, Graham Smith, Eric O Aboagye, Laurence Carroll","doi":"10.2310/7290.2015.00026","DOIUrl":"10.2310/7290.2015.00026","url":null,"abstract":"<p><p>Steroid hormone receptor (SHR) expression and changes in SHR expression compared to basal levels, whether upregulated, downregulated, or mutated, form a distinguishing feature of some breast, ovarian, and prostate cancers. These receptors act to induce tumor proliferation. In the imaging context, total expression together with modulation of expression can yield predictive and prognostic information. Currently, biopsy for histologic assessment of SHR expression is routine for breast and prostate cancer; however, the technique is not well suited to the heterogeneous tumor environment and can lead to incorrect receptor expression assignment, which precludes effective treatment. The development of positron emission tomography (PET) radioligands to image receptor expression may overcome the difficulties associated with tumor heterogeneity and facilitate the assessment of metastatic disease.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"14 10","pages":"534-50"},"PeriodicalIF":2.8,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34188291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[11C]Carfentanil Binds Preferentially to μ-Opioid Receptor Subtype 1 Compared to Subtype 2.","authors":"Olof Eriksson,&nbsp;Gunnar Antoni","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The positron emission tomography (PET) ligand [(11)C]carfentanil is a selective agonist for μ-opioid receptors and has been used for studying μ-opioid receptors in the human brain. However, it is unknown if [(11)C]carfentanil binding differentiates between subtype receptors μ1 and μ2. In this study, we investigated whether μ1 and μ2 can be studied separately through receptor subtype-selective inhibition of [(11)C]carfentanil by pharmacologic intervention. [(11)C]Carfentanil binding characteristics on rat brain sections were assessed either alone or in the presence of the μ-receptor inhibitor cyprodime or the μ1-specific inhibitor naloxonazine. [(11)C]Carfentanil binding in the living rat brain was similarly studied by small animal PET/computed tomography during baseline conditions or following displacement by cyprodime or naloxonazine. Autoradiography binding studies on rat brain sections demonstrated that [(11)C]carfentanil has higher affinity and binding potential for μ1 than for μ2. [(11)C]Carfentanil binding to μ2 in vivo could not be detected following specific blocking of μ1, as predicted from the low binding potential for μ2 as measured in vitro. [(11)C]Carfentanil binding is preferential for μ1 compared to μ2 in vitro and in vivo. Clinical studies employing [(11)C]carfentanil are therefore likely biased to measure μ1 rather than μ2.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"14 ","pages":"476-83"},"PeriodicalIF":2.8,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34251820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Applications for Optically Enabled Intravital Microscopic Imaging in Radiobiology.","authors":"Azusa Maeda,&nbsp;Iris Kulbatski,&nbsp;Ralph S DaCosta","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Radiation therapy is an effective cancer treatment used in over 50% of cancer patients. Preclinical research in radiobiology plays a major role in influencing the translation of radiotherapy-based treatment strategies into clinical practice. Studies have demonstrated that various components of tumors and their microenvironments, including vasculature, immune and stem cells, and stromal cells, can influence the response of solid tumors to radiation. Optically enabled imaging techniques used in experimental animal models of cancer offer a unique and powerful way to quantitatively track spatiotemporal changes in these tumor components in vivo at macro-, meso-, and microscopic resolutions following radiotherapy. In this review, we discuss the role of both well-established and emerging intravital microscopy techniques for studying tumors and their microenvironment in vivo, in response to irradiation. The development and application of new animal models, small animal microirradiation technologies, and multimodal optically enabled intravital microscopy techniques are emphasized within the framework of preclinical radiobiology research. We also comment on the potential influence that these newer imaging techniques may have on the clinical translation of new preclinical radiobiology discoveries.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"14 ","pages":"452-74"},"PeriodicalIF":2.8,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34082898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vulnerable plaque detection and quantification with gold particle-enhanced computed tomography in atherosclerotic mouse models.","authors":"David De Wilde,&nbsp;Bram Trachet,&nbsp;Carole Van der Donckt,&nbsp;Bert Vandeghinste,&nbsp;Benedicte Descamps,&nbsp;Christian Vanhove,&nbsp;Guido R Y De Meyer,&nbsp;Patrick Segers","doi":"10.2310/7290.2015.00009","DOIUrl":"https://doi.org/10.2310/7290.2015.00009","url":null,"abstract":"<p><p>Recently, an apolipoprotein E-deficient (ApoE-/-) mouse model with a mutation (C1039G+/-) in the fibrillin-1 (Fbn1) gene (ApoE-/-Fbn1C1039G+/- mouse model) was developed showing vulnerable atherosclerotic plaques, prone to rupture, in contrast to the ApoE-/- mouse model, where mainly stable plaques are present. One indicator of plaque vulnerability is the level of macrophage infiltration. Therefore, this study aimed to measure and quantify in vivo the macrophage infiltration related to plaque development and progression. For this purpose, 5-weekly consecutive gold nanoparticle-enhanced micro-computed tomography (microCT) scans were acquired. Histology confirmed that the presence of contrast agent coincided with the presence of macrophages. Based on the microCT scans, regions of the artery wall with contrast agent present were calculated and visualized in three dimensions. From this information, the contrast-enhanced area and contrast-enhanced centerline length were calculated for the branches of the carotid bifurcation (common, external, and internal carotid arteries). Statistical analysis showed a more rapid development and a larger extent of plaques in the ApoE-/-Fbn1C1039G+/- compared to the ApoE-/- mice. Regional differences between the branches were also observable and quantifiable. We developed and applied a methodology based on gold particle-enhanced microCT to visualize the presence of macrophages in atherosclerotic plaques in vivo.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"14 ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2310/7290.2015.00009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34180230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vivo Quantification of 5-HT2A Brain Receptors in Mdr1a KO Rats with 123I-R91150 Single-Photon Emission Computed Tomography.","authors":"Noé Dumas,&nbsp;Marcelle Moulin-Sallanon,&nbsp;Pascal Fender,&nbsp;Benjamin B Tournier,&nbsp;Nathalie Ginovart,&nbsp;Yves Charnay,&nbsp;Philippe Millet","doi":"10.2310/7290.2015.00006","DOIUrl":"https://doi.org/10.2310/7290.2015.00006","url":null,"abstract":"<p><p>Our goal was to identify suitable image quantification methods to image 5-hydroxytryptamine2A (5-HT2A) receptors in vivo in Mdr1a knockout (KO) rats (i.e., P-glycoprotein KO) using 123I-R91150 single-photon emission computed tomography (SPECT). The 123I-R91150 binding parameters estimated with different reference tissue models (simplified reference tissue model [SRTM], Logan reference tissue model, and tissue ratio [TR] method) were compared to the estimates obtained with a comprehensive three-tissue/seven-parameter (3T/7k)-based model. The SRTM and Logan reference tissue model estimates of 5-HT2A receptor (5-HT2AR) nondisplaceable binding potential (BPND) correlated well with the absolute receptor density measured with the 3T/7k gold standard (r > .89). Quantification of 5-HT2AR using the Logan reference tissue model required at least 90 minutes of scanning, whereas the SRTM required at least 110 minutes. The TR method estimates were also highly correlated to the 5-HT2AR density (r > .91) and only required a single 20-minute scan between 100 and 120 minutes postinjection. However, a systematic overestimation of the BPND values was observed. The Logan reference tissue method is more convenient than the SRTM for the quantification of 5-HT2AR in Mdr1a KO rats using 123I-R91150 SPECT. The TR method is an interesting and simple alternative, despite its bias, as it still provides a valid index of 5-HT2AR density.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"14 ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2310/7290.2015.00006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34298953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}