Elaine M Jagoda, Olga Vasalatiy, Falguni Basuli, Ana Christina L Opina, Mark R Williams, Karen Wong, Kelly C Lane, Steve Adler, Anita Thein Ton, Lawrence P Szajek, Biying Xu, Donna Butcher, Elijah F Edmondson, Rolf E Swenson, John Greiner, James Gulley, Janet Eary, Peter L Choyke
{"title":"Immuno-PET Imaging of the Programmed Cell Death-1 Ligand (PD-L1) Using a Zirconium-89 Labeled Therapeutic Antibody, Avelumab.","authors":"Elaine M Jagoda, Olga Vasalatiy, Falguni Basuli, Ana Christina L Opina, Mark R Williams, Karen Wong, Kelly C Lane, Steve Adler, Anita Thein Ton, Lawrence P Szajek, Biying Xu, Donna Butcher, Elijah F Edmondson, Rolf E Swenson, John Greiner, James Gulley, Janet Eary, Peter L Choyke","doi":"10.1177/1536012119829986","DOIUrl":"10.1177/1536012119829986","url":null,"abstract":"<p><strong>Objective: </strong>The goal is to evaluate avelumab, an anti-PD-L1 monoclonal immunoglobulin G antibody labeled with zirconium-89 in human PD-L1-expressing cancer cells and mouse xenografts for clinical translation.</p><p><strong>Methods: </strong>[<sup>89</sup>Zr]Zr-DFO-PD-L1 monoclonal antibody (mAb) was synthesized using avelumab conjugated to desferrioxamine. In vitro binding studies and biodistribution studies were performed with PD-L1+MDA-MB231 cells and MDA-MB231 xenograft mouse models, respectively. Biodistributions were determined at 1, 2, 3, 5, and 7 days post coinjection of [<sup>89</sup>Zr]Zr-DFO-PD-L1 mAb without or with unlabeled avelumab (10, 20, 40, and 400 µg).</p><p><strong>Results: </strong>[<sup>89</sup>Zr]Zr-DFO-PD-L1 mAb exhibited high affinity (K<sub>d</sub> ∼ 0.3 nM) and detected moderate PD-L1 expression levels in MDA-MB231 cells. The spleen and lymph nodes exhibited the highest [<sup>89</sup>Zr]Zr-DFO-PD-L1 mAb uptakes in all time points, while MDA-MB231 tumor uptakes were lower but highly retained. In the unlabeled avelumab dose escalation studies, spleen tissue-muscle ratios decreased in a dose-dependent manner indicating specific [<sup>89</sup>Zr]Zr-DFO-PD-L1 mAb binding to PD-L1. In contrast, lymph node and tumor tissue-muscle ratios increased 4- to 5-fold at 20 and 40 µg avelumab doses.</p><p><strong>Conclusions: </strong>[<sup>89</sup>Zr]Zr-DFO-PD-L1 mAb exhibited specific and high affinity for PD-L1 in vitro and had target tissue uptakes correlating with PD-L1 expression levels in vivo. [<sup>89</sup>Zr]Zr-DFO-PD-L1 mAb uptake in PD-L1+tumors increased with escalating doses of avelumab.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"18 ","pages":"1536012119829986"},"PeriodicalIF":2.4,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37203252","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}
Wojciech G Lesniak, Ronnie C Mease, Samit Chatterjee, Dhiraj Kumar, Ala Lisok, Bryan Wharram, Venkateswara Rao Kalagadda, Leisha A Emens, Martin G Pomper, Sridhar Nimmagadda
{"title":"Development of [<sup>18</sup>F]FPy-WL12 as a PD-L1 Specific PET Imaging Peptide.","authors":"Wojciech G Lesniak, Ronnie C Mease, Samit Chatterjee, Dhiraj Kumar, Ala Lisok, Bryan Wharram, Venkateswara Rao Kalagadda, Leisha A Emens, Martin G Pomper, Sridhar Nimmagadda","doi":"10.1177/1536012119852189","DOIUrl":"https://doi.org/10.1177/1536012119852189","url":null,"abstract":"<p><p>Expression of programmed cell death ligand 1 (PD-L1) within tumors is an important biomarker for guiding immune checkpoint therapies; however, immunohistochemistry-based methods of detection fail to provide a comprehensive picture of PD-L1 levels in an entire patient. To facilitate quantification of PD-L1 in the whole body, we developed a peptide-based, high-affinity PD-L1 imaging agent labeled with [<sup>18</sup>F]fluoride for positron emission tomography (PET) imaging. The parent peptide, WL12, and the nonradioactive analog of the radiotracer, <sup>19</sup>FPy-WL12, inhibit PD-1/PD-L1 interaction at low nanomolar concentrations (half maximal inhibitory concentration [IC<sub>50</sub>], 26-32 nM). The radiotracer, [<sup>18</sup>F]FPy-WL12, was prepared by conjugating 2,3,5,6-tetrafluorophenyl 6-[<sup>18</sup>F]fluoronicotinate ([<sup>18</sup>F]FPy-TFP) to WL12 and assessed for specificity in vitro in 6 cancer cell lines with varying PD-L1 expression. The uptake of the radiotracer reflected the PD-L1 expression assessed by flow cytometry. Next, we performed the in vivo evaluation of [<sup>18</sup>F]FPy-WL12 in mice bearing cancer xenografts by PET imaging, ex vivo biodistribution, and blocking studies. In vivo data demonstrated a PD-L1-specific uptake of [<sup>18</sup>F]FPy-WL12 in tumors that is reduced in mice receiving a blocking dose. The majority of [<sup>18</sup>F]FPy-WL12 radioactivity was localized in the tumors, liver, and kidneys indicating the need for optimization of the labeling strategy to improve the in vivo pharmacokinetics of the radiotracer.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"18 ","pages":"1536012119852189"},"PeriodicalIF":2.8,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012119852189","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37322006","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":"Analysis of Progress and Challenges of EGFR-Targeted Molecular Imaging in Cancer With a Focus on Affibody Molecules.","authors":"Weizhi Chen, Baozhong Shen, Xilin Sun","doi":"10.1177/1536012118823473","DOIUrl":"https://doi.org/10.1177/1536012118823473","url":null,"abstract":"<p><p>Epidermal growth factor receptor (EGFR)-targeted cancer therapy requires an accurate estimation of EGFR expression in tumors to identify responsive patients, monitor therapeutic effect, and estimate prognosis. The EGFR molecular imaging is an optimal method for evaluating EGFR expression in vivo accurately and noninvasively. In this review, we discuss the recent advances in EGFR-targeted molecular imaging in cancer, with a special focus on the development of imaging agents, including epidermal growth factor (EGF) ligand, monoclonal antibodies, antibody fragments, Affibody, and small molecules. Each substrate or probe, whether it is an endogenous ligand, antibody, peptide, or small molecule labeled with fluorochrome or radionuclide, has unique advantages and limitations. Antibody-based probes have high affinity but a long metabolic cycle and therefore offer poor imaging quality. Affibody molecules promise to surpass antibody-based probes due to their small size, stable chemical properties, and high affinity to the target. Small-molecule probes are safe, have favorable pharmacokinetics, and show high affinity and specificity, in addition to having an ideal size, but are inadequate for delayed imaging after injection due to their fast clearance.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"18 ","pages":"1536012118823473"},"PeriodicalIF":2.8,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012118823473","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36994956","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}
Taylor J Forrest, Timothy J Desmond, Mohamad Issa, Peter J H Scott, Gregory J Basura
{"title":"Evaluating Cholinergic Receptor Expression in Guinea Pig Primary Auditory and Rostral Belt Cortices After Noise Damage Using [<sup>3</sup>H]Scopolamine and [<sup>18</sup>F]Flubatine Autoradiography.","authors":"Taylor J Forrest, Timothy J Desmond, Mohamad Issa, Peter J H Scott, Gregory J Basura","doi":"10.1177/1536012119848927","DOIUrl":"https://doi.org/10.1177/1536012119848927","url":null,"abstract":"<p><p>Noise-induced hearing loss leads to anatomic and physiologic changes in primary auditory cortex (A1) and the adjacent dorsal rostral belt (RB). Since acetylcholine is known to modulate plasticity in other cortical areas, changes in A1 and RB following noise damage may be due to changes in cholinergic receptor expression. We used [<sup>3</sup>H]scopolamine and [<sup>18</sup>F]flubatine binding to measure muscarinic acetylcholine receptor (mAChR) and nicotinic acetylcholine receptor (nAChR) expression, respectively, in guinea pig A1 and RB 3 weeks following unilateral, left ear noise exposure, and a temporary threshold shift in hearing. [<sup>3</sup>H]Scopolamine binding decreased in right A1 and RB (contralateral to noise) compared to sham controls across all cortical layers. [<sup>18</sup>F]Flubatine binding showed a nonsignificant upward trend in right A1 following noise but only significantly increased in right RB and 2 layers of left RB (ipsilateral to noise). This selective response may ultimately influence cortical plasticity and function. The mechanism(s) by which cholinergic receptors are altered following noise exposure remain unknown. However, these data demonstrate noise exposure may differentially influence mAChRs that typically populate interneurons in A1 and RB more than nAChRs that are traditionally located on thalamocortical projections and provide motivation for cholinergic imaging in clinical patient populations of temporary or permanent hearing loss.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"18 ","pages":"1536012119848927"},"PeriodicalIF":2.8,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012119848927","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37247082","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":"<sup>18</sup>F-FDG PET/CT Quantitative Parameters and Texture Analysis Effectively Differentiate Endometrial Precancerous Lesion and Early-Stage Carcinoma.","authors":"Tong Wang, Hongzan Sun, Yan Guo, Lue Zou","doi":"10.1177/1536012119856965","DOIUrl":"https://doi.org/10.1177/1536012119856965","url":null,"abstract":"<p><strong>Objective: </strong>This study evaluated the metabolic parameters and texture features of fluorodeoxyglucose positron emission tomography-computed tomography (PET/CT) for the diagnosis and differentiation of endometrial atypical hyperplasia (EAH), EAH with field cancerization (FC), and stage 1A endometrial carcinoma (EC 1a).</p><p><strong>Materials and methods: </strong>We retrospectively analyzed the metabolic parameters of PET/CT in 170 patients with diagnoses confirmed by pathology, including 57 cases of EAH (57/170, 33.53%), 45 cases of FC (45/170, 26.47%), and 68 cases of EC 1a (68/170, 40.0%). Then, the texture features of each tumor were extracted and compared with the metabolic parameters and pathological results using nonparametric tests and linear regression analysis. The diagnostic performance was assessed by the area under the curve (AUC) values obtained from receiver operating characteristic analysis.</p><p><strong>Results: </strong>There were moderate positive correlations between the PET standardized uptake values (SUVpeak, SUVmax, and SUVmean) and postoperative pathological features with correlation coefficients (<i>r</i><sub>s</sub>) of 0.663, 0.651, and 0.651, respectively (<i>P</i> < .001). Total lesion glycolysis showed relatively low correlation with pathological characteristics (<i>r</i><sub>s</sub> = 0.476), whereas metabolic tumor volume and age showed the weakest correlations (<i>r</i><sub>s</sub> = 0.186 and 0.232, respectively). To differentiate between the diagnosis of EAH and FC, SUVmax displayed the largest AUC of 0.857 (sensitivity, 82.2%; specificity, 84.2%). Five texture features were screened out as Percentile 40, Percentile 45, InverseDifferenceMoment_AllDirection_offset 1, InverseDifferenceMoment_angle 45_offset 4, and ClusterProminence_angle 135_offset 7 (<i>P</i> < .001) by linear model of texture analysis (AUC = 0.851; specificity = 0.692; sensitivity = 0.871). To differentiate between the diagnoses of FC and EC 1a, SUVpeak displayed the largest AUC of 0.715 (sensitivity, 67.6%; specificity, 77.8%), and 2 texture features were identified as Percentile 10 and CP_angle 135_offset 7 (AUC = 0.819; specificity = 0.871; sensitivity = 0.766; <i>P</i> < .001).</p><p><strong>Conclusions: </strong>SUVmax and SUVpeak had the highest diagnostic values for EAH, FC, and EC 1a compared with the other tested parameters. SUVmax, Percentile 40, Percentile 45, InverseDifferenceMoment_AllDirection_offset 1, InverseDifferenceMoment_angle 45_offset 4, and ClusterProminence_angle 135_offset 7 distinguished EAH from FC. SUVpeak, Percentile 10, and ClusterProminence_angle 135_offset 7 distinguished FC from EC 1a. This study showed that the addition of texture features provides valuable information for differentiating EAH, FC, and EC 1a diagnoses.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"18 ","pages":"1536012119856965"},"PeriodicalIF":2.8,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012119856965","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37327769","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}
Jing Zhao, Zhanwen Zhang, Dahong Nie, Hui Ma, Gongjun Yuan, Shu Su, Shaoyu Liu, Sheng Liu, Ganghua Tang
{"title":"PET Imaging of Hepatocellular Carcinomas: <sup>18</sup>F-Fluoropropionic Acid as a Complementary Radiotracer for <sup>18</sup>F-Fluorodeoxyglucose.","authors":"Jing Zhao, Zhanwen Zhang, Dahong Nie, Hui Ma, Gongjun Yuan, Shu Su, Shaoyu Liu, Sheng Liu, Ganghua Tang","doi":"10.1177/1536012118821032","DOIUrl":"https://doi.org/10.1177/1536012118821032","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the preclinical value of <sup>18</sup>F-fluoropropionic acid (<sup>18</sup>F-FPA) and <sup>18</sup>F-fluorodeoxyglucose (<sup>18</sup>F-FDG) positron emission tomography (PET) for imaging HCCs.</p><p><strong>Methods: </strong>The <sup>18</sup>F-FPA and <sup>18</sup>F-FDG uptake patterns in 3 HCC cell lines (Hep3B, HepG2, and SK-Hep1) were assessed in vitro and in vivo. The <sup>18</sup>F-FPA uptake mechanism was investigated using inhibition experiments with orlistat and 5-tetradecyloxy-2-furoic acid. The <sup>18</sup>F-FPA PET imaging was performed in different tumor animal models and compared with <sup>18</sup>F-FDG. We also evaluated the expressions of glucose transporter-1 (GLUT1), fatty acid synthase (FASN), and matrix metalloproteinase-2 (MMP2) in these cell lines.</p><p><strong>Results: </strong>In vitro experiments showed that the radiotracer uptake patterns were complementary in the HCC cell lines. Orlistat and 5-tetradecyloxy-2-furoic acid decreased the uptake of <sup>18</sup>F-FPA. The tumor-to-liver ratio of <sup>18</sup>F-FPA was superior to that of <sup>18</sup>F-FDG in the SK-Hep1 and HepG2 tumors ( P < .05). However, in the Hep3B tumors, the tumor-to-liver normalized uptake of <sup>18</sup>F-FDG was higher than <sup>18</sup>F-FPA ( P < .01). FASN was highly expressed in cell lines with high <sup>18</sup>F-FPA uptake, whereas GLUT1 was highly expressed in cell lines with high <sup>18</sup>F-FDG uptake. The <sup>18</sup>F-FPA uptake correlated with FASN ( r = 0.89, P = .014) and MMP2 ( r = 0.77, P = .002) expressions.</p><p><strong>Conclusions: </strong>PET imaging with <sup>18</sup>F-FPA combined with <sup>18</sup>F-FDG can be an alternative for detecting HCC.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"18 ","pages":"1536012118821032"},"PeriodicalIF":2.8,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012118821032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36994950","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":"Prognostic and Predictive Values of Metabolic Parameters of <sup>18</sup>F-FDG PET/CT in Patients With Non-Small Cell Lung Cancer Treated With Chemotherapy.","authors":"Xueyan Li, Dawei Wang, Lijuan Yu","doi":"10.1177/1536012119846025","DOIUrl":"https://doi.org/10.1177/1536012119846025","url":null,"abstract":"<p><strong>Objectives: </strong>Increasing interests have been focused on using artificial intelligence (AI) to extend prognostic value of medical imaging. Feature extraction is a critical step for successful application of AI. The aim of this study was to explore several metabolic parameters measured by <sup>18</sup>F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) as potential AI features in predicting the effectiveness of chemotherapy in patients with non-small cell lung cancer (NSCLC).</p><p><strong>Methods: </strong>A set of metabolic parameters of PET/CT and clinical characteristics were detected from 137 patients with NSCLC treated with at least 1 cycle of chemotherapy. Survival receiver-operating characteristic (ROC) analysis was used to define the more significant parameters chosen for the following survival analysis. Patient survival was analyzed by Kaplan-Meier method, log-rank test, and Cox regression.</p><p><strong>Results: </strong>Survival ROC showed that maximum standardized uptake value (SUVmax), metabolic tumor volume 50% (MTV50), and total lesion glycolysis 50% (TLG50) had larger area under the curve, and the optimal cutoff values were 11.72, 4.04, and 34.55, respectively. Univariate and multivariate analyses synergistically showed that late PET/CT stage and MTV50 >4.04 were independent factors of poor survival in patients with NSCLC who received chemotherapy.</p><p><strong>Conclusions: </strong>Several potential prognostic biomarkers of PET/CT imaging have been extracted for predicting survival and selecting patients with NSCLC who are more likely to benefit from chemotherapy. The identification may accelerate the development of AI methods to improve treatment outcome for NSCLC.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"18 ","pages":"1536012119846025"},"PeriodicalIF":2.8,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012119846025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37286895","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":"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":"18 ","pages":"1536012118820421"},"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}
Martin G Strebl, Jane Yang, Lyle Isaacs, Jacob M Hooker
{"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":"17 ","pages":"1536012118799838"},"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}
{"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":"17 ","pages":"1536012118808644"},"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}