Challenges in Pharmacokinetic Modelling of [18F]fluoro-PEG-folate PET/CT Imaging in Epithelial Ovarian Cancer Patients

Author:

Ruytenberg ThomasORCID,Ciggaar Isabeau A.,Peters Inge T. A.,Noortman Wyanne A.,Dibbets-Schneider Petra,de Muynck Lysanne D. A. N.,Kuil Joeri,de Kroon Cornelis D.,Molenaar Tom J. M.,Helmerhorst Hendrik J. F.,Pereira Arias-Bouda Lenka M.,Vahrmeijer Alexander L.,Windhorst Albert D.,van Velden Floris H. P.,Gaarenstroom Katja N.,de Geus-Oei Lioe-Fee

Abstract

Abstract 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.

Funder

Bontius Stichting

Publisher

Springer Science and Business Media LLC

Reference14 articles.

1. Colombo N, Sessa C, du Bois A et al; ESMO-ESGO Ovarian Cancer Consensus Conference Working Group (2019) ESMO-ESGO Consensus Conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease. Ann Oncol 30(5):672–705. https://doi.org/10.1093/annonc/mdz062.

2. Wright AA, Bohlke K, Armstrong DK et al (2016) Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian Cancer: Society of Gynecologic Oncology and American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 34(28):3460–3473. https://doi.org/10.1200/JCO.2016.68.6907

3. Du Bois A, Reuss A, Pujade-Lauraine E et al (2009) Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d’Investigateurs Nationaux Pour les Etudes des Cancers de l’Ovaire (GINECO). Cancer 115(6):1234–1244. https://doi.org/10.1002/cncr.24149

4. Muynck LDAN, Gaarenstroom KN, Sier CFM et al (2020) Novel Molecular Targets for Tumor-Specific Imaging of Epithelial Ovarian Cancer Metastases. Cancers (Basel) 12(6):1562. https://doi.org/10.3390/cancers12061562

5. Despierre E, Lambrechts S, Leunen K et al (2013) Folate receptor alpha (FRA) expression remains unchanged in epithelial ovarian and endometrial cancer after chemotherapy. Gynecol Oncol 130(1):192–199. https://doi.org/10.1016/j.ygyno.2013.03.024

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3