| Added by | JPPOUGET |
|---|---|
| Group name | EquipeJPP |
| Item Type | Journal Article |
| Title | Clinical Pharmacokinetics of Radiopharmaceuticals from SPECT/CT Image Acquisition by Contouring in Patients with Gastroenteropancreatic Neuroendocrine Tumors: Lu-177 DOTATATE (Lutathera®) Case |
| Creator | Barakat et al. |
| Author | Anissa Barakat |
| Author | Lore Santoro |
| Author | Myrtille Vivien |
| Author | Pierre-Olivier Kotzki |
| Author | Emmanuel Deshayes |
| Author | Sonia Khier |
| 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. |
| Publication | European Journal of Drug Metabolism and Pharmacokinetics |
| Volume | 48 |
| Issue | 4 |
| Pages | 329-339 |
| Date | 2023-07 |
| Journal Abbr | Eur J Drug Metab Pharmacokinet |
| Language | eng |
| DOI | 10.1007/s13318-023-00829-5 |
| ISSN | 2107-0180 |
| Short Title | Clinical Pharmacokinetics of Radiopharmaceuticals from SPECT/CT Image Acquisition by Contouring in Patients with Gastroenteropancreatic Neuroendocrine Tumors |
| Library Catalog | PubMed |
| Extra | PMID: 37184824 |
| Tags | clinic, Humans, Intestinal Neoplasms, Lutetium, Neuroendocrine Tumors, Pancreatic Neoplasms, Radioisotopes, Radiopharmaceuticals, Retrospective Studies, Stomach Neoplasms, Tissue Distribution, Tomography, Emission-Computed, Single-Photon, Tomography, X-Ray Computed |
| Date Added | 2024/12/07 - 07:58:03 |
| Date Modified | 2024/12/15 - 11:19:23 |
| Notes and Attachments | PubMed entry (Attachment) PubMed entry (Attachment) PubMed entry (Attachment) |
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