Thomas Ruytenberg, Isabeau A Ciggaar, Inge T A Peters, Wyanne A Noortman, Petra Dibbets-Schneider, Lysanne D A N de Muynck, Joeri Kuil, Cornelis D de Kroon, Tom J M Molenaar, Hendrik J F Helmerhorst, Lenka M Pereira Arias-Bouda, Alexander L Vahrmeijer, Albert D Windhorst, Floris H P van Velden, Katja N Gaarenstroom, Lioe-Fee de Geus-Oei
{"title":"上皮性卵巢癌患者[18F]氟-PEG-叶酸 PET/CT 成像药代动力学建模的挑战。","authors":"Thomas Ruytenberg, Isabeau A Ciggaar, Inge T A Peters, Wyanne A Noortman, Petra Dibbets-Schneider, Lysanne D A N de Muynck, Joeri Kuil, Cornelis D de Kroon, Tom J M Molenaar, Hendrik J F Helmerhorst, Lenka M Pereira Arias-Bouda, Alexander L Vahrmeijer, Albert D Windhorst, Floris H P van Velden, Katja N Gaarenstroom, Lioe-Fee de Geus-Oei","doi":"10.1007/s11307-024-01922-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>To describe the pharmacokinetic properties of the [<sup>18</sup>F]fluoro-polyethylene glycol(PEG)-folate radiotracer in PET/CT imaging of patients with advanced stage epithelial ovarian cancer (EOC).</p><p><strong>Procedures: </strong>In five patients with advanced EOC (FIGO stage IIIB/IIIC, Fédération Internationale de Gynécologie et d'Obstétrique), a 90-min dynamic PET acquisition of the pelvis was performed directly after i.v. administration of 185 MBq [<sup>18</sup>F]fluoro-PEG<sub>6</sub>-folate. Arterial blood samples collected at nineteen timepoints were used to determine the plasma input function. A static volume of interest (VOI) for included tumor lesions was drawn manually on the PET images. Modelling was performed using PMOD software. Three different models (a 1-tissue compartment model (1T2k) and two 2-tissue compartment models, irreversible (2T3k) and reversible (2T4k)) were compared in goodness of fit with the time activity curves by means of the Akaike information criterion.</p><p><strong>Results: </strong>The pharmacokinetic analysis in the pelvic area has proven to be much more challenging than expected. Only four out of 22 tumor lesions in five patients were considered suitable to perform modelling on. The remaining tumor lesions were inapt due to either low tracer uptake, small size, proximity to other [<sup>18</sup>F]fluoro-PEG<sub>6</sub>-folate -avid structures and/or displacement by abdominal organ motion in the dynamic scan. Data from the four analyzed tumor lesions suggest that the irreversible 2T3k may best describe the pharmacokinetics. All 22 lesions were immunohistochemically stained positive for the folate receptor alpha (FRα) after resection.</p><p><strong>Conclusion: </strong>Performing pharmacokinetic analysis in the abdominal pelvic region is very challenging. This brief article describes the challenges and pitfalls in pharmacokinetic analysis of a tracer with high physiological accumulation in the intestines, in case of lesions of limited size in the abdominal pelvic area.</p>","PeriodicalId":18760,"journal":{"name":"Molecular Imaging and Biology","volume":" ","pages":"577-584"},"PeriodicalIF":3.0000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282117/pdf/","citationCount":"0","resultStr":"{\"title\":\"Challenges in Pharmacokinetic Modelling of [<sup>18</sup>F]fluoro-PEG-folate PET/CT Imaging in Epithelial Ovarian Cancer Patients.\",\"authors\":\"Thomas Ruytenberg, Isabeau A Ciggaar, Inge T A Peters, Wyanne A Noortman, Petra Dibbets-Schneider, Lysanne D A N de Muynck, Joeri Kuil, Cornelis D de Kroon, Tom J M Molenaar, Hendrik J F Helmerhorst, Lenka M Pereira Arias-Bouda, Alexander L Vahrmeijer, Albert D Windhorst, Floris H P van Velden, Katja N Gaarenstroom, Lioe-Fee de Geus-Oei\",\"doi\":\"10.1007/s11307-024-01922-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>To describe the pharmacokinetic properties of the [<sup>18</sup>F]fluoro-polyethylene glycol(PEG)-folate radiotracer in PET/CT imaging of patients with advanced stage epithelial ovarian cancer (EOC).</p><p><strong>Procedures: </strong>In five patients with advanced EOC (FIGO stage IIIB/IIIC, Fédération Internationale de Gynécologie et d'Obstétrique), a 90-min dynamic PET acquisition of the pelvis was performed directly after i.v. administration of 185 MBq [<sup>18</sup>F]fluoro-PEG<sub>6</sub>-folate. Arterial blood samples collected at nineteen timepoints were used to determine the plasma input function. A static volume of interest (VOI) for included tumor lesions was drawn manually on the PET images. Modelling was performed using PMOD software. Three different models (a 1-tissue compartment model (1T2k) and two 2-tissue compartment models, irreversible (2T3k) and reversible (2T4k)) were compared in goodness of fit with the time activity curves by means of the Akaike information criterion.</p><p><strong>Results: </strong>The pharmacokinetic analysis in the pelvic area has proven to be much more challenging than expected. Only four out of 22 tumor lesions in five patients were considered suitable to perform modelling on. The remaining tumor lesions were inapt due to either low tracer uptake, small size, proximity to other [<sup>18</sup>F]fluoro-PEG<sub>6</sub>-folate -avid structures and/or displacement by abdominal organ motion in the dynamic scan. Data from the four analyzed tumor lesions suggest that the irreversible 2T3k may best describe the pharmacokinetics. All 22 lesions were immunohistochemically stained positive for the folate receptor alpha (FRα) after resection.</p><p><strong>Conclusion: </strong>Performing pharmacokinetic analysis in the abdominal pelvic region is very challenging. This brief article describes the challenges and pitfalls in pharmacokinetic analysis of a tracer with high physiological accumulation in the intestines, in case of lesions of limited size in the abdominal pelvic area.</p>\",\"PeriodicalId\":18760,\"journal\":{\"name\":\"Molecular Imaging and Biology\",\"volume\":\" \",\"pages\":\"577-584\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282117/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Imaging and Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11307-024-01922-0\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/5/22 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/s11307-024-01922-0","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/22 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
Challenges in Pharmacokinetic Modelling of [18F]fluoro-PEG-folate PET/CT Imaging in Epithelial Ovarian Cancer Patients.
Purpose: To describe the pharmacokinetic properties of the [18F]fluoro-polyethylene glycol(PEG)-folate radiotracer in PET/CT imaging of patients with advanced stage epithelial ovarian cancer (EOC).
Procedures: In five patients with advanced EOC (FIGO stage IIIB/IIIC, Fédération Internationale de Gynécologie et d'Obstétrique), a 90-min dynamic PET acquisition of the pelvis was performed directly after i.v. administration of 185 MBq [18F]fluoro-PEG6-folate. Arterial blood samples collected at nineteen timepoints were used to determine the plasma input function. A static volume of interest (VOI) for included tumor lesions was drawn manually on the PET images. Modelling was performed using PMOD software. Three different models (a 1-tissue compartment model (1T2k) and two 2-tissue compartment models, irreversible (2T3k) and reversible (2T4k)) were compared in goodness of fit with the time activity curves by means of the Akaike information criterion.
Results: The pharmacokinetic analysis in the pelvic area has proven to be much more challenging than expected. Only four out of 22 tumor lesions in five patients were considered suitable to perform modelling on. The remaining tumor lesions were inapt due to either low tracer uptake, small size, proximity to other [18F]fluoro-PEG6-folate -avid structures and/or displacement by abdominal organ motion in the dynamic scan. Data from the four analyzed tumor lesions suggest that the irreversible 2T3k may best describe the pharmacokinetics. All 22 lesions were immunohistochemically stained positive for the folate receptor alpha (FRα) after resection.
Conclusion: Performing pharmacokinetic analysis in the abdominal pelvic region is very challenging. This brief article describes the challenges and pitfalls in pharmacokinetic analysis of a tracer with high physiological accumulation in the intestines, in case of lesions of limited size in the abdominal pelvic area.
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.
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