Arutselvan Natarajan, Shyam M Srinivas, Carmen Azevedo, Lacey Greene, Anne-Laure Bauchet, Erwan Jouannot, Anne-Sophie Lacoste-Bourgeacq, Isabelle Guizon, Patrick Cohen, Anne-Laure Naneix, Ohad Ilovich, Jordan Cisneros, Krithika Rupanarayan, Frederick T Chin, Andrei Iagaru, Frederick M Dirbas, Amer Karam, Sanjiv S Gambhir
{"title":"Two Patient Studies of a Companion Diagnostic Immuno-Positron Emission Tomography (PET) Tracer for Measuring Human CA6 Expression in Cancer for Antibody Drug Conjugate (ADC) Therapy.","authors":"Arutselvan Natarajan, Shyam M Srinivas, Carmen Azevedo, Lacey Greene, Anne-Laure Bauchet, Erwan Jouannot, Anne-Sophie Lacoste-Bourgeacq, Isabelle Guizon, Patrick Cohen, Anne-Laure Naneix, Ohad Ilovich, Jordan Cisneros, Krithika Rupanarayan, Frederick T Chin, Andrei Iagaru, Frederick M Dirbas, Amer Karam, Sanjiv S Gambhir","doi":"10.1177/1536012120939398","DOIUrl":"https://doi.org/10.1177/1536012120939398","url":null,"abstract":"<p><p>An antigen binding fragment (BFab) derived from a tumor-associated mucin 1-sialoglycotope antigen (CA6) targeting antibody (huDS6) was engineered. We synthesized a companion diagnostic positron emission tomography (PET) tracer by radiolabeling BFab with [<sup>64</sup>Cu] to measure CA6 expression on cancer tissues prior to anti-human CA6 (huDS6-DM4 antibody-drug conjugate) therapy for ovarian and breast cancer patients. After chemotherapy, the ovarian patient received PET scan with <sup>18</sup>F-2-fluoro-2-deoxyglucose ([<sup>18</sup>F]FDG: 10 mCi), followed by [<sup>64</sup>Cu]-DOTA-BFab ([<sup>64</sup>Cu]BFab; 5.5 mCi) 1 week later for PET scanning of CA6 expression and subsequent surgery. The breast cancer patient was treated with chemotherapy before primary tumor resection and subsequent [<sup>18</sup>F]FDG-PET scan. 4 weeks later the patient received of [<sup>64</sup>Cu]BFab (11.7 mCi) for CA6 PET scan. Whole body [<sup>18</sup>F]FDG-PET of the breast cancer patient indicated FDG-avid tumor metastases to the liver, bilateral hila and thoracic spine, but no uptake was observed for the ovarian patient. Each patient was also imaged by PET/CT with [<sup>64</sup>Cu]BFab at 1 and 24 hours after tracer administration. The [<sup>64</sup>Cu]BFab tracer was well tolerated by both patients without adverse effects, and no significant tracer uptake was observed in both patients. Immunohistochemistry (IHC) data indicated CA6 expressions were weak to intermediate and matched with the [<sup>64</sup>Cu]BFab-PET signals.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"19 ","pages":"1536012120939398"},"PeriodicalIF":2.8,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012120939398","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38625616","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":"High-Efficiency Production of Radiopharmaceuticals via Droplet Radiochemistry: A Review of Recent Progress.","authors":"Jia Wang, R Michael van Dam","doi":"10.1177/1536012120973099","DOIUrl":"10.1177/1536012120973099","url":null,"abstract":"<p><p>New platforms are enabling radiochemistry to be carried out in tiny, microliter-scale volumes, and this capability has enormous benefits for the production of radiopharmaceuticals. These droplet-based technologies can achieve comparable or better yields compared to conventional methods, but with vastly reduced reagent consumption, shorter synthesis time, higher molar activity (even for low activity batches), faster purification, and ultra-compact system size. We review here the state of the art of this emerging direction, summarize the radiotracers and prosthetic groups that have been synthesized in droplet format, describe recent achievements in scaling up activity levels, and discuss advantages and limitations and the future outlook of these innovative devices.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"19 ","pages":"1536012120973099"},"PeriodicalIF":2.8,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012120973099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38353405","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}
Florian van Beurden, Danny M van Willigen, Borivoj Vojnovic, Matthias N van Oosterom, Oscar R Brouwer, Henk G van der Poel, Hisataka Kobayashi, Fijs W B van Leeuwen, Tessa Buckle
{"title":"Multi-Wavelength Fluorescence in Image-Guided Surgery, Clinical Feasibility and Future Perspectives.","authors":"Florian van Beurden, Danny M van Willigen, Borivoj Vojnovic, Matthias N van Oosterom, Oscar R Brouwer, Henk G van der Poel, Hisataka Kobayashi, Fijs W B van Leeuwen, Tessa Buckle","doi":"10.1177/1536012120962333","DOIUrl":"10.1177/1536012120962333","url":null,"abstract":"<p><p>With the rise of fluorescence-guided surgery, it has become evident that different types of fluorescence signals can provide value in the surgical setting. Hereby a different range of targets have been pursued in a great variety of surgical indications. One of the future challenges lies in combining complementary fluorescent readouts during one and the same surgical procedure, so-called multi-wavelength fluorescence guidance. In this review we summarize the current clinical state-of-the-art in multi-wavelength fluorescence guidance, basic technical concepts, possible future extensions of existing clinical indications and impact that the technology can bring to clinical care.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"19 ","pages":"1536012120962333"},"PeriodicalIF":2.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/75/d5/10.1177_1536012120962333.PMC7607779.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38548284","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}
Mucong Li, Nikhila Nyayapathi, Hailey I Kilian, Jun Xia, Jonathan F Lovell, Junjie Yao
{"title":"Sound Out the Deep Colors: Photoacoustic Molecular Imaging at New Depths.","authors":"Mucong Li, Nikhila Nyayapathi, Hailey I Kilian, Jun Xia, Jonathan F Lovell, Junjie Yao","doi":"10.1177/1536012120981518","DOIUrl":"https://doi.org/10.1177/1536012120981518","url":null,"abstract":"Photoacoustic tomography (PAT) has become increasingly popular for molecular imaging due to its unique optical absorption contrast, high spatial resolution, deep imaging depth, and high imaging speed. Yet, the strong optical attenuation of biological tissues has traditionally prevented PAT from penetrating more than a few centimeters and limited its application for studying deeply seated targets. A variety of PAT technologies have been developed to extend the imaging depth, including employing deep-penetrating microwaves and X-ray photons as excitation sources, delivering the light to the inside of the organ, reshaping the light wavefront to better focus into scattering medium, as well as improving the sensitivity of ultrasonic transducers. At the same time, novel optical fluence mapping algorithms and image reconstruction methods have been developed to improve the quantitative accuracy of PAT, which is crucial to recover weak molecular signals at larger depths. The development of highly-absorbing near-infrared PA molecular probes has also flourished to provide high sensitivity and specificity in studying cellular processes. This review aims to introduce the recent developments in deep PA molecular imaging, including novel imaging systems, image processing methods and molecular probes, as well as their representative biomedical applications. Existing challenges and future directions are also discussed.","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"19 ","pages":"1536012120981518"},"PeriodicalIF":2.8,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012120981518","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38725464","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}
Shiyu Tang, Elizabeth M Powell, Wenjun Zhu, Fu-Sun Lo, Reha S Erzurumlu, Su Xu
{"title":"Altered Forebrain Functional Connectivity and Neurotransmission in a Kinase-Inactive Met Mouse Model of Autism.","authors":"Shiyu Tang, Elizabeth M Powell, Wenjun Zhu, Fu-Sun Lo, Reha S Erzurumlu, Su Xu","doi":"10.1177/1536012118821034","DOIUrl":"10.1177/1536012118821034","url":null,"abstract":"<p><p>MET, the gene encoding the tyrosine kinase receptor for hepatocyte growth factor, is a susceptibility gene for autism spectrum disorder (ASD). Genetically altered mice with a kinase-inactive Met offer a potential model for understanding neural circuit organization changes in autism. Here, we focus on the somatosensory thalamocortical circuitry because distinct somatosensory sensitivity phenotypes accompany ASD, and this system plays a major role in sensorimotor and social behaviors in mice. We employed resting-state functional magnetic resonance imaging and in vivo high-resolution proton MR spectroscopy to examine neuronal connectivity and neurotransmission of wild-type, heterozygous Met-Emx1, and fully inactive homozygous Met-Emx1 mice. Met-Emx1 brains showed impaired maturation of large-scale somatosensory network connectivity when compared with wild-type controls. Significant sex × genotype interaction in both network features and glutamate/gamma-aminobutyric acid (GABA) balance was observed. Female Met-Emx1 brains showed significant connectivity and glutamate/GABA balance changes in the somatosensory thalamocortical system when compared with wild-type brains. The glutamate/GABA ratio in the thalamus was correlated with the connectivity between the somatosensory cortex and the thalamus in heterozygous Met-Emx1 female brains. The findings support the hypothesis that aberrant functioning of the somatosensory thalamocortical system is at the core of the conspicuous somatosensory behavioral phenotypes observed in Met-Emx1 mice.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"18 ","pages":"1536012118821034"},"PeriodicalIF":2.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e9/8a/10.1177_1536012118821034.PMC6322103.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36994952","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}
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":"https://doi.org/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":2.8,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012119829986","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}