Objective: Oxidative stress plays an important role in the onset of many neuronal and peripheral disorders. We examined the feasibility of obtaining semiquantitative fluorescent images of reactive oxygen species (ROS) generation in mouse brain and kidney utilizing a planar laser scanner and dihydroethidium (DHE).
Methods: To investigate ROS generation in brain, sodium nitroprusside was injected into the striatum. Dihydroethidium was injected into the tail vein. After DHE injection, tissue slices were analyzed utilizing a planar laser scanner. For kidney study, cis-diamminedichloroplatinum [II] (cisplatin) was intraperitoneally administrated into mice.
Results: Clear and semiquantitative fluorescent images of ROS generation in the mouse brain and kidney were obtained. Furthermore, the fluorescence intensity was stable and not affected by fading. Sodium nitroprusside induced approximately 6 times the fluorescence accumulation in the brain. Cisplatin caused renal injury in all mice, and in comparison with control mice, more than 10 times fluorescence accumulation was observed in the renal medulla with tubular necrosis and vacuolization.
Conclusions: We successfully obtained ex vivo semiquantitative fluorescent images of ROS generation utilizing a planar laser scanner and DHE. This simple method is useful for ROS detection in several ROS-related animal models and would be applicable to a variety of biochemical processes.
{"title":"A Simple Ex Vivo Semiquantitative Fluorescent Imaging Utilizing Planar Laser Scanner: Detection of Reactive Oxygen Species Generation in Mouse Brain and Kidney.","authors":"Rie Hosoi, Sota Sato, Miho Shukuri, Yuka Fujii, Kenichiro Todoroki, Yasushi Arano, Toshihiro Sakai, Osamu Inoue","doi":"10.1177/1536012118820421","DOIUrl":"https://doi.org/10.1177/1536012118820421","url":null,"abstract":"<p><strong>Objective: </strong>Oxidative stress plays an important role in the onset of many neuronal and peripheral disorders. We examined the feasibility of obtaining semiquantitative fluorescent images of reactive oxygen species (ROS) generation in mouse brain and kidney utilizing a planar laser scanner and dihydroethidium (DHE).</p><p><strong>Methods: </strong>To investigate ROS generation in brain, sodium nitroprusside was injected into the striatum. Dihydroethidium was injected into the tail vein. After DHE injection, tissue slices were analyzed utilizing a planar laser scanner. For kidney study, cis-diamminedichloroplatinum [II] (cisplatin) was intraperitoneally administrated into mice.</p><p><strong>Results: </strong>Clear and semiquantitative fluorescent images of ROS generation in the mouse brain and kidney were obtained. Furthermore, the fluorescence intensity was stable and not affected by fading. Sodium nitroprusside induced approximately 6 times the fluorescence accumulation in the brain. Cisplatin caused renal injury in all mice, and in comparison with control mice, more than 10 times fluorescence accumulation was observed in the renal medulla with tubular necrosis and vacuolization.</p><p><strong>Conclusions: </strong>We successfully obtained ex vivo semiquantitative fluorescent images of ROS generation utilizing a planar laser scanner and DHE. This simple method is useful for ROS detection in several ROS-related animal models and would be applicable to a variety of biochemical processes.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012118820421","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36994955","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}
Pub Date : 2018-01-01DOI: 10.1177/1536012118799838
Martin G Strebl, Jane Yang, Lyle Isaacs, Jacob M Hooker
Positron emission tomography (PET) imaging with biological macromolecules greatly expands the possibilities of molecular imaging. There are, however, practical aspects limiting the potential of the approach, including the dosimetric consequences of the slow kinetics of radiolabeled biomacromolecules. Pretargeting strategies have led to impactful improvements in the field but are themselves limited by shortcomings of available bioconjugation methodology. We report our initial findings concerning the suitability of the adamantane/cucurbit[7]uril system for pretargeted immuno-PET imaging and provide proof-of-concept PET/computed tomography imaging experiments to establish the stability and rapid formation of host-guest complexes in vivo. The adamantane/cucurbit[7]uril system itself without antibody conjugation has shown remarkably fast association kinetics and clearance in vivo. We further demonstrate the modulation of biodistribution achievable by cucurbituril complexation with relevance for pharmaceutical formulation as well as the radiosynthetic access to relevant reporter molecules labeled with 11C or 18F. This work, an early proof-of-concept, supports the notion that the adamantane/cucurbit[7]uril system warrants further exploration in pretargeted PET imaging applications.
{"title":"Adamantane/Cucurbituril: A Potential Pretargeted Imaging Strategy in Immuno-PET.","authors":"Martin G Strebl, Jane Yang, Lyle Isaacs, Jacob M Hooker","doi":"10.1177/1536012118799838","DOIUrl":"https://doi.org/10.1177/1536012118799838","url":null,"abstract":"<p><p>Positron emission tomography (PET) imaging with biological macromolecules greatly expands the possibilities of molecular imaging. There are, however, practical aspects limiting the potential of the approach, including the dosimetric consequences of the slow kinetics of radiolabeled biomacromolecules. Pretargeting strategies have led to impactful improvements in the field but are themselves limited by shortcomings of available bioconjugation methodology. We report our initial findings concerning the suitability of the adamantane/cucurbit[7]uril system for pretargeted immuno-PET imaging and provide proof-of-concept PET/computed tomography imaging experiments to establish the stability and rapid formation of host-guest complexes in vivo. The adamantane/cucurbit[7]uril system itself without antibody conjugation has shown remarkably fast association kinetics and clearance in vivo. We further demonstrate the modulation of biodistribution achievable by cucurbituril complexation with relevance for pharmaceutical formulation as well as the radiosynthetic access to relevant reporter molecules labeled with <sup>11</sup>C or <sup>18</sup>F. This work, an early proof-of-concept, supports the notion that the adamantane/cucurbit[7]uril system warrants further exploration in pretargeted PET imaging applications.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012118799838","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36657252","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}
Oral cancer is one of the most common cancers globally. Survival rates for patients are directly correlated with stage of diagnosis; despite this knowledge, 60% of individuals are presenting with late-stage disease. Currently, the initial evaluation of a questionable lesion is performed by a conventional visual examination with white light. If a lesion is deemed suspicious, a biopsy is taken for diagnosis. However, not all lesions present suspicious under visual white light examination, and there is limited specificity in differentiating between benign and malignant transformations. Several vital dyes, light-based detection systems, and cytology evaluation methods have been formulated to aid in the visualization process, but their lack of specific biomarkers resulted in high false-positive rates and thus limits their reliability as screening and guidance tools. In this review, we will analyze the current methodologies and demonstrate the need for specific intraoral imaging agents to aid in screening and diagnosis to identify patients earlier. Several novel molecular imaging agents will be presented as, by result of their molecular targeting, they aim to have high specificity for tumor pathways and can support in identifying dysplastic/cancerous lesions and guiding visualization of biopsy sites. Imaging agents that are easy to use, inexpensive, noninvasive, and specific can be utilized to increase the number of patients who are screened and monitored in a variety of different environments, with the ultimate goal of increasing early detection.
{"title":"Current Practice and Emerging Molecular Imaging Technologies in Oral Cancer Screening.","authors":"Arianna Strome, Susanne Kossatz, Daniella Karassawa Zanoni, Milind Rajadhyaksha, Snehal Patel, Thomas Reiner","doi":"10.1177/1536012118808644","DOIUrl":"https://doi.org/10.1177/1536012118808644","url":null,"abstract":"<p><p>Oral cancer is one of the most common cancers globally. Survival rates for patients are directly correlated with stage of diagnosis; despite this knowledge, 60% of individuals are presenting with late-stage disease. Currently, the initial evaluation of a questionable lesion is performed by a conventional visual examination with white light. If a lesion is deemed suspicious, a biopsy is taken for diagnosis. However, not all lesions present suspicious under visual white light examination, and there is limited specificity in differentiating between benign and malignant transformations. Several vital dyes, light-based detection systems, and cytology evaluation methods have been formulated to aid in the visualization process, but their lack of specific biomarkers resulted in high false-positive rates and thus limits their reliability as screening and guidance tools. In this review, we will analyze the current methodologies and demonstrate the need for specific intraoral imaging agents to aid in screening and diagnosis to identify patients earlier. Several novel molecular imaging agents will be presented as, by result of their molecular targeting, they aim to have high specificity for tumor pathways and can support in identifying dysplastic/cancerous lesions and guiding visualization of biopsy sites. Imaging agents that are easy to use, inexpensive, noninvasive, and specific can be utilized to increase the number of patients who are screened and monitored in a variety of different environments, with the ultimate goal of increasing early detection.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012118808644","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38411601","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}
Pub Date : 2018-01-01DOI: 10.1177/1536012118809585
Anne Herrmann, Arthur Taylor, Patricia Murray, Harish Poptani, Violaine Sée
Metastasis is the most common cause of death for patients with cancer. To fully understand the steps involved in metastatic dissemination, in vivo models are required, of which murine ones are the most common. Therefore, preclinical imaging methods such as magnetic resonance imaging (MRI) have mainly been developed for small mammals and their potential to monitor cancer growth and metastasis in nonmammalian models is not fully harnessed. We have here used MRI to measure primary neuroblastoma tumor size and metastasis in a chick embryo model. We compared its sensitivity and accuracy to end-point fluorescence detection upon dissection. Human neuroblastoma cells labeled with green fluorescent protein (GFP) and micron-sized iron particles were implanted on the extraembryonic chorioallantoic membrane of the chick at E7. T2 RARE, T2-weighted fast low angle shot (FLASH) as well as time-of-flight MR angiography imaging were applied at E14. Micron-sized iron particle labeling of neuroblastoma cells allowed in ovo observation of the primary tumor and tumor volume measurement noninvasively. Moreover, T2 weighted and FLASH imaging permitted the detection of small metastatic deposits in the chick embryo, thereby reinforcing the potential of this convenient, 3R compliant, in vivo model for cancer research.
{"title":"Magnetic Resonance Imaging for Characterization of a Chick Embryo Model of Cancer Cell Metastases.","authors":"Anne Herrmann, Arthur Taylor, Patricia Murray, Harish Poptani, Violaine Sée","doi":"10.1177/1536012118809585","DOIUrl":"https://doi.org/10.1177/1536012118809585","url":null,"abstract":"<p><p>Metastasis is the most common cause of death for patients with cancer. To fully understand the steps involved in metastatic dissemination, in vivo models are required, of which murine ones are the most common. Therefore, preclinical imaging methods such as magnetic resonance imaging (MRI) have mainly been developed for small mammals and their potential to monitor cancer growth and metastasis in nonmammalian models is not fully harnessed. We have here used MRI to measure primary neuroblastoma tumor size and metastasis in a chick embryo model. We compared its sensitivity and accuracy to end-point fluorescence detection upon dissection. Human neuroblastoma cells labeled with green fluorescent protein (GFP) and micron-sized iron particles were implanted on the extraembryonic chorioallantoic membrane of the chick at E7. T<sub>2</sub> RARE, T<sub>2</sub>-weighted fast low angle shot (FLASH) as well as time-of-flight MR angiography imaging were applied at E14. Micron-sized iron particle labeling of neuroblastoma cells allowed in ovo observation of the primary tumor and tumor volume measurement noninvasively. Moreover, T<sub>2</sub> weighted and FLASH imaging permitted the detection of small metastatic deposits in the chick embryo, thereby reinforcing the potential of this convenient, 3R compliant, in vivo model for cancer research.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012118809585","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36634021","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}
Pub Date : 2018-01-01DOI: 10.1177/1536012118795728
Ying Xiong, Dahong Nie, Shaoyu Liu, Hui Ma, Shu Su, Aixia Sun, Jing Zhao, Zhanwen Zhang, Xianhong Xiang, Ganghua Tang
Objective: To investigate the value of 2-(3-[18F]fluoropropyl)-2-methyl-malonic acid ([18F]ML-8) positron emission tomography (PET) imaging of rat pulmonary fibrosis.
Methods: Male Sprague-Dawley rats were divided into 2 groups, including pulmonary fibrosis model group and control group. The rat model was established by an intratracheal instillation of bleomycin (BLM). Control rats were treated with saline. Positron emission tomography/computed tomography (CT) with [18F]ML-8 or 18F-fluorodeoxyglucose ([18F]FDG) was performed on 2 groups. After PET/CT imaging, lung tissues were collected for histologic examination. Data were analyzed and comparisons between 2 groups were performed using Student t test.
Results: Bleomycin-treated rats showed a higher lung uptake of [18F]ML-8 than control rats ( P < .05). In BLM-treated rats, the lung to muscle relative uptake ratio of [18F]ML-8 was also higher than that of [18F]FDG ( P < .05). Pathological examination showed overproliferation of fibroblasts and deposition of collagen in lungs from BLM-treated rats. Compared to control rats, BLM-treated rats had higher lung hydroxyproline content ( P < .05). Immunofluorescence staining indicated more apoptotic cells in BLM-treated rats than those in control rats. Moreover, the apoptosis rate of lung tissues obtained from BLM-treated rats was higher than that from control rats ( P < .05).
Conclusions: 2-(3-[18F]fluoropropyl)-2-methyl-malonic acid PET/CT could be used for noninvasive diagnosis of pulmonary fibrosis in a rat model.
{"title":"Apoptotic PET Imaging of Rat Pulmonary Fibrosis With [<sup>18</sup>F]ML-8.","authors":"Ying Xiong, Dahong Nie, Shaoyu Liu, Hui Ma, Shu Su, Aixia Sun, Jing Zhao, Zhanwen Zhang, Xianhong Xiang, Ganghua Tang","doi":"10.1177/1536012118795728","DOIUrl":"https://doi.org/10.1177/1536012118795728","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the value of 2-(3-[<sup>18</sup>F]fluoropropyl)-2-methyl-malonic acid ([<sup>18</sup>F]ML-8) positron emission tomography (PET) imaging of rat pulmonary fibrosis.</p><p><strong>Methods: </strong>Male Sprague-Dawley rats were divided into 2 groups, including pulmonary fibrosis model group and control group. The rat model was established by an intratracheal instillation of bleomycin (BLM). Control rats were treated with saline. Positron emission tomography/computed tomography (CT) with [<sup>18</sup>F]ML-8 or <sup>18</sup>F-fluorodeoxyglucose ([<sup>18</sup>F]FDG) was performed on 2 groups. After PET/CT imaging, lung tissues were collected for histologic examination. Data were analyzed and comparisons between 2 groups were performed using Student t test.</p><p><strong>Results: </strong>Bleomycin-treated rats showed a higher lung uptake of [<sup>18</sup>F]ML-8 than control rats ( P < .05). In BLM-treated rats, the lung to muscle relative uptake ratio of [<sup>18</sup>F]ML-8 was also higher than that of [<sup>18</sup>F]FDG ( P < .05). Pathological examination showed overproliferation of fibroblasts and deposition of collagen in lungs from BLM-treated rats. Compared to control rats, BLM-treated rats had higher lung hydroxyproline content ( P < .05). Immunofluorescence staining indicated more apoptotic cells in BLM-treated rats than those in control rats. Moreover, the apoptosis rate of lung tissues obtained from BLM-treated rats was higher than that from control rats ( P < .05).</p><p><strong>Conclusions: </strong>2-(3-[<sup>18</sup>F]fluoropropyl)-2-methyl-malonic acid PET/CT could be used for noninvasive diagnosis of pulmonary fibrosis in a rat model.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012118795728","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36606465","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}
Pub Date : 2018-01-01DOI: 10.1177/1536012118809587
Ahmed Abbas, Lihai Yu, Tyler Lalonde, Derek Wu, Jonathan D Thiessen, Leonard G Luyt, Savita Dhanvantari
One-third of patients with heart disease develop heart failure, which is diagnosed through imaging and detection of circulating biomarkers. Imaging strategies reveal morphologic and functional changes but fall short of detecting molecular abnormalities that can lead to heart failure, and circulating biomarkers are not cardiac specific. Thus, there is critical need for biomarkers that are endogenous to myocardial tissues. The cardiac growth hormone secretagogue receptor 1a (GHSR1a), which binds the hormone ghrelin, is a potential biomarker for heart failure. We have synthesized and characterized a novel ghrelin peptidomimetic tracer, an 18F-labeled analogue of G-7039, for positron emission tomography (PET) imaging of cardiac GHSR1a. In vitro analysis showed enhanced serum stability compared to natural ghrelin and significantly increased cellular uptake in GHSR1a-expressing OVCAR cells. Biodistribution studies in mice showed that tissue uptake of the tracer was independent of circulating ghrelin levels, and there was negligible cardiac uptake and high uptake in the liver, intestines, and kidneys. Specificity of tracer uptake was assessed using ghsr -/- mice; both static and dynamic PET imaging revealed no difference in cardiac uptake, and there was no significant correlation between cardiac standardized uptake values and GHSR1a expression. Our study lays the groundwork for further refinement of peptidomimetic PET tracers targeting cardiac GHSR1a.
{"title":"Development and Characterization of an <sup>18</sup>F-labeled Ghrelin Peptidomimetic for Imaging the Cardiac Growth Hormone Secretagogue Receptor.","authors":"Ahmed Abbas, Lihai Yu, Tyler Lalonde, Derek Wu, Jonathan D Thiessen, Leonard G Luyt, Savita Dhanvantari","doi":"10.1177/1536012118809587","DOIUrl":"https://doi.org/10.1177/1536012118809587","url":null,"abstract":"<p><p>One-third of patients with heart disease develop heart failure, which is diagnosed through imaging and detection of circulating biomarkers. Imaging strategies reveal morphologic and functional changes but fall short of detecting molecular abnormalities that can lead to heart failure, and circulating biomarkers are not cardiac specific. Thus, there is critical need for biomarkers that are endogenous to myocardial tissues. The cardiac growth hormone secretagogue receptor 1a (GHSR1a), which binds the hormone ghrelin, is a potential biomarker for heart failure. We have synthesized and characterized a novel ghrelin peptidomimetic tracer, an <sup>18</sup>F-labeled analogue of G-7039, for positron emission tomography (PET) imaging of cardiac GHSR1a. In vitro analysis showed enhanced serum stability compared to natural ghrelin and significantly increased cellular uptake in GHSR1a-expressing OVCAR cells. Biodistribution studies in mice showed that tissue uptake of the tracer was independent of circulating ghrelin levels, and there was negligible cardiac uptake and high uptake in the liver, intestines, and kidneys. Specificity of tracer uptake was assessed using ghsr <sup>-/-</sup> mice; both static and dynamic PET imaging revealed no difference in cardiac uptake, and there was no significant correlation between cardiac standardized uptake values and GHSR1a expression. Our study lays the groundwork for further refinement of peptidomimetic PET tracers targeting cardiac GHSR1a.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012118809587","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36648356","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}
Pub Date : 2018-01-01DOI: 10.1177/1536012118801223
Kendra S Carmon, Ali Azhdarinia
Targeted therapies hold great promise for cancer treatment and may exhibit even greater efficacy when combined with patient selection tools. The clinical impact of identifying likely responders includes reducing the number of unnecessary and ineffective therapies as well as more accurately determining drug effects. Positron emission tomography (PET) imaging using zirconium-89 radiolabeled monoclonal antibodies (mAbs), also referred to as zirconium-89 (89Zr)-immuno-PET, provides a potential biomarker to measure target expression and verify optimal delivery of targeted agents to tumors. Antibody-drug conjugates (ADCs) combine the high affinity and specificity of mAbs with the potency of cytotoxic drugs to target tumor-expressing antigen and destroy cancer cells. Thus, 89Zr-immuno-PET of whole-body biodistribution, pharmacokinetics, and tumor targeting of antibodies and ADCs to predict toxicity and efficacy could help guide individualized treatment. Here, we review how 89Zr-immuno-PET is being used as a companion diagnostic with the development of ADCs. Furthermore, we discuss how 89Zr-immuno-PET may be utilized in future clinical trials as an adjunct tool with novel ADCs to select cancer patients who have the greatest potential to benefit from treatment and improve ADC dosing regimens.
{"title":"Application of Immuno-PET in Antibody-Drug Conjugate Development.","authors":"Kendra S Carmon, Ali Azhdarinia","doi":"10.1177/1536012118801223","DOIUrl":"https://doi.org/10.1177/1536012118801223","url":null,"abstract":"<p><p>Targeted therapies hold great promise for cancer treatment and may exhibit even greater efficacy when combined with patient selection tools. The clinical impact of identifying likely responders includes reducing the number of unnecessary and ineffective therapies as well as more accurately determining drug effects. Positron emission tomography (PET) imaging using zirconium-89 radiolabeled monoclonal antibodies (mAbs), also referred to as zirconium-89 (<sup>89</sup>Zr)-immuno-PET, provides a potential biomarker to measure target expression and verify optimal delivery of targeted agents to tumors. Antibody-drug conjugates (ADCs) combine the high affinity and specificity of mAbs with the potency of cytotoxic drugs to target tumor-expressing antigen and destroy cancer cells. Thus, <sup>89</sup>Zr-immuno-PET of whole-body biodistribution, pharmacokinetics, and tumor targeting of antibodies and ADCs to predict toxicity and efficacy could help guide individualized treatment. Here, we review how <sup>89</sup>Zr-immuno-PET is being used as a companion diagnostic with the development of ADCs. Furthermore, we discuss how <sup>89</sup>Zr-immuno-PET may be utilized in future clinical trials as an adjunct tool with novel ADCs to select cancer patients who have the greatest potential to benefit from treatment and improve ADC dosing regimens.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012118801223","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36670854","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}
Pub Date : 2018-01-01DOI: 10.1177/1536012118802721
Liliya M Yamaleyeva, K Bridget Brosnihan, Lane M Smith, Yao Sun
Placental oxygenation varies throughout pregnancy. The detection of early changes in placental oxygenation as pregnancy progresses is important for early identification of preeclampsia or other complications. This invited commentary discusses a recent preclinical study on the application of 3-dimensional photoacoustic imaging (PAI) for assessment of regional variations in placental oxygenation and longitudinal analysis of differences in placental oxygenation throughout normal pregnancy and pregnancy associated with hypertension or placental insufficiency in mice. Three-dimensional PAI more accurately reflects oxygen saturation, hemoglobin concentrations, and changes in oxygen saturation in whole placenta compared to 2-dimensional imaging. These studies suggest that PAI is a sensitive tool to detect different levels of oxygen saturation in the placental and fetal vasculature in pathologic and normal pregnancy in mice.
胎盘氧合在整个孕期都会发生变化。随着妊娠的进展,检测胎盘氧合的早期变化对于早期识别子痫前期或其他并发症非常重要。这篇特邀评论讨论了最近的一项临床前研究,该研究应用三维光声成像(PAI)评估胎盘氧合的区域变化,并纵向分析正常妊娠和妊娠合并高血压或胎盘功能不全小鼠胎盘氧合的差异。与二维成像相比,三维 PAI 能更准确地反映整个胎盘的血氧饱和度、血红蛋白浓度和血氧饱和度的变化。这些研究表明,PAI 是检测小鼠病理妊娠和正常妊娠中胎盘和胎儿血管中不同氧饱和度水平的灵敏工具。
{"title":"Preclinical Ultrasound-Guided Photoacoustic Imaging of the Placenta in Normal and Pathologic Pregnancy.","authors":"Liliya M Yamaleyeva, K Bridget Brosnihan, Lane M Smith, Yao Sun","doi":"10.1177/1536012118802721","DOIUrl":"10.1177/1536012118802721","url":null,"abstract":"<p><p>Placental oxygenation varies throughout pregnancy. The detection of early changes in placental oxygenation as pregnancy progresses is important for early identification of preeclampsia or other complications. This invited commentary discusses a recent preclinical study on the application of 3-dimensional photoacoustic imaging (PAI) for assessment of regional variations in placental oxygenation and longitudinal analysis of differences in placental oxygenation throughout normal pregnancy and pregnancy associated with hypertension or placental insufficiency in mice. Three-dimensional PAI more accurately reflects oxygen saturation, hemoglobin concentrations, and changes in oxygen saturation in whole placenta compared to 2-dimensional imaging. These studies suggest that PAI is a sensitive tool to detect different levels of oxygen saturation in the placental and fetal vasculature in pathologic and normal pregnancy in mice.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/13/fa/10.1177_1536012118802721.PMC6201183.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36606466","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}
Pub Date : 2017-01-01DOI: 10.1177/1536012117723786
Susanne Kossatz, Wolfgang Weber, Thomas Reiner
More sensitive and specific methods for early detection are imperative to improve survival rates in oral cancer. However, oral cancer detection is still largely based on visual examination and histopathology of biopsy material, offering no molecular selectivity or spatial resolution. Intuitively, the addition of optical contrast could improve oral cancer detection and delineation, but so far no molecularly targeted approach has been translated. Our fluorescently labeled small-molecule inhibitor PARPi-FL binds to the DNA repair enzyme poly(ADP-ribose)polymerase 1 (PARP1) and is a potential diagnostic aid for oral cancer delineation. Based on our preclinical work, a clinical phase I/II trial opened in March 2017 to evaluate PARPi-FL as a contrast agent for oral cancer imaging. In this commentary, we discuss why we chose PARP1 as a biomarker for tumor detection and which particular characteristics make PARPi-FL an excellent candidate to image PARP1 in optically guided applications. We also comment on the potential benefits of our molecularly targeted PARPi-FL-guided imaging approach in comparison to existing oral cancer screening adjuncts and mention the adaptability of PARPi-FL imaging to other environments and tumor types.
{"title":"Detection and Delineation of Oral Cancer With a PARP1-Targeted Optical Imaging Agent.","authors":"Susanne Kossatz, Wolfgang Weber, Thomas Reiner","doi":"10.1177/1536012117723786","DOIUrl":"https://doi.org/10.1177/1536012117723786","url":null,"abstract":"<p><p>More sensitive and specific methods for early detection are imperative to improve survival rates in oral cancer. However, oral cancer detection is still largely based on visual examination and histopathology of biopsy material, offering no molecular selectivity or spatial resolution. Intuitively, the addition of optical contrast could improve oral cancer detection and delineation, but so far no molecularly targeted approach has been translated. Our fluorescently labeled small-molecule inhibitor PARPi-FL binds to the DNA repair enzyme poly(ADP-ribose)polymerase 1 (PARP1) and is a potential diagnostic aid for oral cancer delineation. Based on our preclinical work, a clinical phase I/II trial opened in March 2017 to evaluate PARPi-FL as a contrast agent for oral cancer imaging. In this commentary, we discuss why we chose PARP1 as a biomarker for tumor detection and which particular characteristics make PARPi-FL an excellent candidate to image PARP1 in optically guided applications. We also comment on the potential benefits of our molecularly targeted PARPi-FL-guided imaging approach in comparison to existing oral cancer screening adjuncts and mention the adaptability of PARPi-FL imaging to other environments and tumor types.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012117723786","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35313104","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}
Pub Date : 2017-01-01DOI: 10.1177/1536012117711369
Huaifu Deng, Hui Wang, He Zhang, Mengzhe Wang, Ben Giglio, Xiaofen Ma, Guihua Jiang, Hong Yuan, Zhanhong Wu, Zibo Li
Introduction: Neurotensin receptor 1 (NTR-1) is expressed and activated in prostate cancer cells. In this study, we explore the NTR expression in normal mouse tissues and study the positron emission tomography (PET) imaging of NTR in prostate cancer models.
Materials and methods: Three 64Cu chelators (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid [DOTA], 1,4,7-triazacyclononane-N,N',N″-triacetic acid [NOTA], or AmBaSar) were conjugated to an NT analog. Neurotensin receptor binding affinity was evaluated using cell binding assay. The imaging profile of radiolabeled probes was compared in well-established NTR+ HT-29 tumor model. Stability of the probes was tested. The selected agents were further evaluated in human prostate cancer PC3 xenografts.
Results: All 3 NT conjugates retained the majority of NTR binding affinity. In HT-29 tumor, all agents demonstrated prominent tumor uptake. Although comparable stability was observed, 64Cu-NOTA-NT and 64Cu-AmBaSar-NT demonstrated improved tumor to background contrast compared with 64Cu-DOTA-NT. Positron emission tomography/computed tomography imaging of the NTR expression in PC-3 xenografts showed high tumor uptake of the probes, correlating with the in vitro Western blot results. Blocking experiments further confirmed receptor specificity.
Conclusions: Our results demonstrated that 64Cu-labeled neurotensin analogs are promising imaging agents for NTR-positive tumors. These agents may help us identify NTR-positive lesions and predict which patients and individual tumors are likely to respond to novel interventions targeting NTR-1.
{"title":"Imaging Neurotensin Receptor in Prostate Cancer With <sup>64</sup>Cu-Labeled Neurotensin Analogs.","authors":"Huaifu Deng, Hui Wang, He Zhang, Mengzhe Wang, Ben Giglio, Xiaofen Ma, Guihua Jiang, Hong Yuan, Zhanhong Wu, Zibo Li","doi":"10.1177/1536012117711369","DOIUrl":"https://doi.org/10.1177/1536012117711369","url":null,"abstract":"<p><strong>Introduction: </strong>Neurotensin receptor 1 (NTR-1) is expressed and activated in prostate cancer cells. In this study, we explore the NTR expression in normal mouse tissues and study the positron emission tomography (PET) imaging of NTR in prostate cancer models.</p><p><strong>Materials and methods: </strong>Three <sup>64</sup>Cu chelators (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid [DOTA], 1,4,7-triazacyclononane-N,N',N″-triacetic acid [NOTA], or AmBaSar) were conjugated to an NT analog. Neurotensin receptor binding affinity was evaluated using cell binding assay. The imaging profile of radiolabeled probes was compared in well-established NTR<sup>+</sup> HT-29 tumor model. Stability of the probes was tested. The selected agents were further evaluated in human prostate cancer PC3 xenografts.</p><p><strong>Results: </strong>All 3 NT conjugates retained the majority of NTR binding affinity. In HT-29 tumor, all agents demonstrated prominent tumor uptake. Although comparable stability was observed, <sup>64</sup>Cu-NOTA-NT and <sup>64</sup>Cu-AmBaSar-NT demonstrated improved tumor to background contrast compared with <sup>64</sup>Cu-DOTA-NT. Positron emission tomography/computed tomography imaging of the NTR expression in PC-3 xenografts showed high tumor uptake of the probes, correlating with the in vitro Western blot results. Blocking experiments further confirmed receptor specificity.</p><p><strong>Conclusions: </strong>Our results demonstrated that <sup>64</sup>Cu-labeled neurotensin analogs are promising imaging agents for NTR-positive tumors. These agents may help us identify NTR-positive lesions and predict which patients and individual tumors are likely to respond to novel interventions targeting NTR-1.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012117711369","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35306925","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}