Tianzhe Li, Grace A Murley, Xiaofei Liang, Renee L Chin, Jorge de la Cerda, F William Schuler, Mark D Pagel
{"title":"利用氧增强电子顺磁共振成像(OE EPRI)评估肿瘤病理生理学对放疗反应的早期变化。","authors":"Tianzhe Li, Grace A Murley, Xiaofei Liang, Renee L Chin, Jorge de la Cerda, F William Schuler, Mark D Pagel","doi":"10.1007/s11307-024-01925-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Electron Paramagnetic Resonance Imaging (EPRI) can image the partial pressure of oxygen (pO<sub>2</sub>) within in vivo tumor models. We sought to develop Oxygen Enhanced (OE) EPRI that measures tumor pO<sub>2</sub> with breathing gases of 21% O<sub>2</sub> (pO<sub>2</sub><sup>21%</sup>) and 100% O<sub>2</sub> (pO<sub>2</sub><sup>100%</sup>), and the differences in pO<sub>2</sub> between breathing gases (ΔpO<sub>2</sub>). We applied OE EPRI to study the early change in tumor pathophysiology in response to radiotherapy in two tumor models of pancreatic cancer.</p><p><strong>Procedures: </strong>We developed a protocol that intraperitoneally administered OX071, a trityl radical contrast agent, and then acquired anatomical MR images to localize the tumor. Subsequently, we acquired two pO<sub>2</sub><sup>21%</sup> and two pO<sub>2</sub><sup>100%</sup> maps using the T1 relaxation time of OX071 measured with EPRI and a R<sub>1</sub>-pO<sub>2</sub> calibration of OX071. We studied 4T1 flank tumor model to evaluate the repeatability of OE EPRI. We then applied OE EPRI to study COLO 357 and Su.86.86 flank tumor models treated with 10 Gy radiotherapy.</p><p><strong>Results: </strong>The repeatability of mean pO<sub>2</sub> for individual tumors was ± 2.6 Torr between successive scans when breathing 21% O<sub>2</sub> or 100% O<sub>2</sub>, representing a precision of 9.6%. Tumor pO<sub>2</sub><sup>21%</sup> and pO<sub>2</sub><sup>100%</sup> decreased after radiotherapy for both models, although the decreases were not significant or only moderately significant, and the effect sizes were modest. For comparison, ΔpO<sub>2</sub> showed a large, highly significant decrease after radiotherapy, and the effect size was large. MANOVA and analyses of the HF10 hypoxia fraction provided similar results.</p><p><strong>Conclusions: </strong>EPRI can evaluate tumor pO<sub>2</sub> with outstanding precision relative to other imaging modalities. The change in ΔpO<sub>2</sub> before vs. after treatment was the best parameter for measuring the early change in tumor pathophysiology in response to radiotherapy. Our studies have established ΔpO<sub>2</sub> from OE EPRI as a new parameter, and have established that OE EPRI is a valuable new methodology for molecular imaging.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"448-458"},"PeriodicalIF":3.0000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11830149/pdf/","citationCount":"0","resultStr":"{\"title\":\"Evaluations of an Early Change in Tumor Pathophysiology in Response to Radiotherapy with Oxygen Enhanced Electron Paramagnetic Resonance Imaging (OE EPRI).\",\"authors\":\"Tianzhe Li, Grace A Murley, Xiaofei Liang, Renee L Chin, Jorge de la Cerda, F William Schuler, Mark D Pagel\",\"doi\":\"10.1007/s11307-024-01925-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Electron Paramagnetic Resonance Imaging (EPRI) can image the partial pressure of oxygen (pO<sub>2</sub>) within in vivo tumor models. We sought to develop Oxygen Enhanced (OE) EPRI that measures tumor pO<sub>2</sub> with breathing gases of 21% O<sub>2</sub> (pO<sub>2</sub><sup>21%</sup>) and 100% O<sub>2</sub> (pO<sub>2</sub><sup>100%</sup>), and the differences in pO<sub>2</sub> between breathing gases (ΔpO<sub>2</sub>). We applied OE EPRI to study the early change in tumor pathophysiology in response to radiotherapy in two tumor models of pancreatic cancer.</p><p><strong>Procedures: </strong>We developed a protocol that intraperitoneally administered OX071, a trityl radical contrast agent, and then acquired anatomical MR images to localize the tumor. Subsequently, we acquired two pO<sub>2</sub><sup>21%</sup> and two pO<sub>2</sub><sup>100%</sup> maps using the T1 relaxation time of OX071 measured with EPRI and a R<sub>1</sub>-pO<sub>2</sub> calibration of OX071. We studied 4T1 flank tumor model to evaluate the repeatability of OE EPRI. We then applied OE EPRI to study COLO 357 and Su.86.86 flank tumor models treated with 10 Gy radiotherapy.</p><p><strong>Results: </strong>The repeatability of mean pO<sub>2</sub> for individual tumors was ± 2.6 Torr between successive scans when breathing 21% O<sub>2</sub> or 100% O<sub>2</sub>, representing a precision of 9.6%. Tumor pO<sub>2</sub><sup>21%</sup> and pO<sub>2</sub><sup>100%</sup> decreased after radiotherapy for both models, although the decreases were not significant or only moderately significant, and the effect sizes were modest. For comparison, ΔpO<sub>2</sub> showed a large, highly significant decrease after radiotherapy, and the effect size was large. MANOVA and analyses of the HF10 hypoxia fraction provided similar results.</p><p><strong>Conclusions: </strong>EPRI can evaluate tumor pO<sub>2</sub> with outstanding precision relative to other imaging modalities. The change in ΔpO<sub>2</sub> before vs. after treatment was the best parameter for measuring the early change in tumor pathophysiology in response to radiotherapy. Our studies have established ΔpO<sub>2</sub> from OE EPRI as a new parameter, and have established that OE EPRI is a valuable new methodology for molecular imaging.</p>\",\"PeriodicalId\":18760,\"journal\":{\"name\":\"Molecular Imaging and Biology\",\"volume\":\" \",\"pages\":\"448-458\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2024-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11830149/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Imaging and Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11307-024-01925-x\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/6/13 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Imaging and Biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11307-024-01925-x","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/13 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
Evaluations of an Early Change in Tumor Pathophysiology in Response to Radiotherapy with Oxygen Enhanced Electron Paramagnetic Resonance Imaging (OE EPRI).
Purpose: Electron Paramagnetic Resonance Imaging (EPRI) can image the partial pressure of oxygen (pO2) within in vivo tumor models. We sought to develop Oxygen Enhanced (OE) EPRI that measures tumor pO2 with breathing gases of 21% O2 (pO221%) and 100% O2 (pO2100%), and the differences in pO2 between breathing gases (ΔpO2). We applied OE EPRI to study the early change in tumor pathophysiology in response to radiotherapy in two tumor models of pancreatic cancer.
Procedures: We developed a protocol that intraperitoneally administered OX071, a trityl radical contrast agent, and then acquired anatomical MR images to localize the tumor. Subsequently, we acquired two pO221% and two pO2100% maps using the T1 relaxation time of OX071 measured with EPRI and a R1-pO2 calibration of OX071. We studied 4T1 flank tumor model to evaluate the repeatability of OE EPRI. We then applied OE EPRI to study COLO 357 and Su.86.86 flank tumor models treated with 10 Gy radiotherapy.
Results: The repeatability of mean pO2 for individual tumors was ± 2.6 Torr between successive scans when breathing 21% O2 or 100% O2, representing a precision of 9.6%. Tumor pO221% and pO2100% decreased after radiotherapy for both models, although the decreases were not significant or only moderately significant, and the effect sizes were modest. For comparison, ΔpO2 showed a large, highly significant decrease after radiotherapy, and the effect size was large. MANOVA and analyses of the HF10 hypoxia fraction provided similar results.
Conclusions: EPRI can evaluate tumor pO2 with outstanding precision relative to other imaging modalities. The change in ΔpO2 before vs. after treatment was the best parameter for measuring the early change in tumor pathophysiology in response to radiotherapy. Our studies have established ΔpO2 from OE EPRI as a new parameter, and have established that OE EPRI is a valuable new methodology for molecular imaging.
期刊介绍:
Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures.
Some areas that are covered are:
Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes.
The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets.
Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display.
Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging.
Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics.
Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations.
Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.