Clinical Pharmacokinetics of Radiopharmaceuticals from SPECT/CT Image Acquisition by Contouring in Patients with Gastroenteropancreatic Neuroendocrine Tumors: Lu-177 DOTATATE (Lutathera®) Case.

IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Anissa Barakat, Lore Santoro, Myrtille Vivien, Pierre-Olivier Kotzki, Emmanuel Deshayes, Sonia Khier
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引用次数: 0

Abstract

Background and objective: Lu-177 DOTATATE (Lutathera®) is a radiolabeled analog of somatostatin administered intravenously in patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. Biodistribution of Lu-177 DOTATATE in tumor and healthy tissues can be monitored by serial post-injection scintigraphy imaging. Patient exposure to the drug is variable with the recommended fixed dosage, and hence there is a variable response to treatment. The aim of this work was to study the pharmacokinetics of Lu-177 DOTATATE by a population modeling approach, based on single-photon emission computed tomography (SPECT)/computed tomography (CT) images used as surrogate of plasma concentrations to study the interindividual variability and finally optimize an individual dosage.

Methods: From a retrospective study, SPECT/CT images were acquired at 4 h, 24 h, 72 h, and 192 h postadministration. From these images, volumic activities were calculated in blood and bone marrow. An individual non-compartmental pharmacokinetic analysis was performed, and the mean pharmacokinetic parameters of each tissue were compared together and with reference data. Blood volumic activities were then used to perform a population pharmacokinetic analysis (NONMEM).

Results: The pharmacokinetic parameters (non-compartmental analysis) obtained from blood (clearance [CL] = 2.65 L/h, volume of distribution at steady state [Vss] = 309 L, elimination half-life [t1/2] = 86.3 h) and bone marrow (CL =1.68 L/h, Vss = 233 L, t1/2 = 98.8 h) were statistically different from each other and from reference values (CL = 4.50 L/h, Vss = 460 L, t1/2 = 71.0 h) published in the literature. SPECT/CT blood images were used as a surrogate of plasma concentrations to develop a population pharmacokinetic model. Weight was identified as covariate on volume of the central compartment, reducing the interindividual variability of all population pharmacokinetic parameters.

Conclusion: This study is a proof of concept that obtaining pharmacokinetic parameters with image-based blood concentration is possible. Obtaining observed concentrations from SPECT/CT images, without the need for blood sampling, is a real advantage for the patient and the drug monitoring. Pharmacokinetic modeling could be combined with a deep learning model for automatic contouring and allow precise patient-specific dose adjustment in a non-invasive manner.

Abstract Image

胃肠胰神经内分泌肿瘤患者SPECT/CT图像轮廓获取放射药物的临床药代动力学:Lutathera®病例。
背景和目的:Lu-177 DOTATATE (Lutathera®)是一种放射标记的生长抑素类似物,用于生长抑素受体阳性的胃肠胰腺神经内分泌肿瘤患者静脉注射。lu177 DOTATATE在肿瘤和健康组织中的生物分布可以通过连续注射后的闪烁成像来监测。患者对药物的暴露随推荐的固定剂量而变化,因此对治疗的反应也不同。本研究的目的是通过群体建模方法研究lu177 DOTATATE的药代动力学,基于单光子发射计算机断层扫描(SPECT)/计算机断层扫描(CT)图像作为血浆浓度的替代,研究个体间的变异性,最终优化个体剂量。方法:通过回顾性研究,分别在给药后4小时、24小时、72小时和192小时采集SPECT/CT图像。根据这些图像,计算血液和骨髓中的体积活动。进行个体非室区药代动力学分析,并将各组织的平均药代动力学参数与参考数据进行比较。然后使用血容量活动进行人群药代动力学分析(NONMEM)。结果:血液(清除率[CL] = 2.65 L/h,稳态分布体积[Vss] = 309 L,消除半衰期[t1/2] = 86.3 h)和骨髓(CL =1.68 L/h, Vss = 233 L, t1/2 = 98.8 h)的药代动力学参数(非区室分析)与文献中发表的参考值(CL = 4.50 L/h, Vss = 460 L, t1/2 = 71.0 h)差异均有统计学意义。使用SPECT/CT血液图像作为血浆浓度的替代品来建立人群药代动力学模型。体重被确定为中央室体积的协变量,减少了所有群体药代动力学参数的个体间变异性。结论:本研究证明了通过图像血药浓度获得药代动力学参数是可能的。从SPECT/CT图像中获得观察到的浓度,而不需要血液采样,这对患者和药物监测来说是一个真正的优势。药代动力学建模可以与深度学习模型相结合,实现自动轮廓,并以无创方式精确调整患者特定剂量。
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来源期刊
CiteScore
3.70
自引率
0.00%
发文量
64
审稿时长
>12 weeks
期刊介绍: Hepatology International is a peer-reviewed journal featuring articles written by clinicians, clinical researchers and basic scientists is dedicated to research and patient care issues in hepatology. This journal focuses mainly on new and emerging diagnostic and treatment options, protocols and molecular and cellular basis of disease pathogenesis, new technologies, in liver and biliary sciences. Hepatology International publishes original research articles related to clinical care and basic research; review articles; consensus guidelines for diagnosis and treatment; invited editorials, and controversies in contemporary issues. The journal does not publish case reports.
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