دورية أكاديمية
أعرض في EDS

Assessment of mouse-specific pharmacokinetics in kidneys based on 131 I activity measurements using micro-SPECT.

التفاصيل البيبلوغرافية
العنوان: Assessment of mouse-specific pharmacokinetics in kidneys based on 131 I activity measurements using micro-SPECT.
المؤلفون: Vargas CS; Radiation Protection Dosimetry and Calibrations, Belgian Nuclear Research Centre (SCK CEN), Boeretang 200, 2400, Mol, Belgium. csvargas@sckcen.be.; Laboratory for In Vivo Cellular and Molecular Imaging, Department of Medical Imaging, Vrije Universiteit Brussel, Brussels, Belgium. csvargas@sckcen.be., Struelens L; Radiation Protection Dosimetry and Calibrations, Belgian Nuclear Research Centre (SCK CEN), Boeretang 200, 2400, Mol, Belgium., D'Huyvetter M; Laboratory for In Vivo Cellular and Molecular Imaging, Department of Medical Imaging, Vrije Universiteit Brussel, Brussels, Belgium., Caveliers V; Laboratory for In Vivo Cellular and Molecular Imaging, Department of Medical Imaging, Vrije Universiteit Brussel, Brussels, Belgium., Covens P; Laboratory for In Vivo Cellular and Molecular Imaging, Department of Medical Imaging, Vrije Universiteit Brussel, Brussels, Belgium.
المصدر: EJNMMI physics [EJNMMI Phys] 2022 Feb 23; Vol. 9 (1), pp. 13. Date of Electronic Publication: 2022 Feb 23.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer-Verlag, GmbH Country of Publication: Germany NLM ID: 101658952 Publication Model: Electronic Cited Medium: Print ISSN: 2197-7364 (Print) Linking ISSN: 21977364 NLM ISO Abbreviation: EJNMMI Phys Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Heidelberg, Germany : Springer-Verlag, GmbH, [2014]-
مستخلص: Background: In order to acquire accurate drug pharmacokinetic information, which is required for tissue dosimetry, micro-SPECT must be quantitative to allow for an accurate assessment of radioligand activity in the relevant tissue. This study investigates the feasibility of deriving accurate mouse-specific time-integrated drug pharmacokinetic data in mouse kidneys from activity measurements using micro-SPECT.
Methods: An animal experiment was carried out to evaluate the accuracy of 131 I activity quantification in mouse kidneys (mean tissue volume of 0.140 mL) using a micro-SPECT system against conventional ex vivo gamma counting (GC) in a NaI(Tl) detector. The imaging setting investigated was that of the mouse biodistribution of a 131 I-labelled single-domain antibody fragment (sdAb), currently being investigated for targeted radionuclide therapy of HER2-expressing cancer. SPECT imaging of 131 I 365-keV photons was done with a VECTor/CT system (MILabs, Netherlands) using a high-energy mouse collimator with 1.6-mm-diameter pinholes. For both activity quantification techniques, the pharmacokinetic profile of the radioligand from approximately 1-73 h p.i. was derived and the time-integrated activity coefficient per gram of tissue (ã/M) was estimated. Additionally, SPECT activity recovery coefficients were determined in a phantom setting.
Results: SPECT activities underestimate the reference activities by an amount that is dependent on the 131 I activity concentration in the kidney, and thus on the time point of the pharmacokinetic profile. This underestimation is around - 12% at 1.5 h (2.89 MBq mL -1 mean reference activity concentration), - 13% at 6.6 h (149 kBq mL -1 ), - 40% at 24 h (17.6 kBq mL -1 ) and - 46% at 73 h (5.2 kBq mL -1 ) p.i. The ã/M value estimated from SPECT activities is, nevertheless, within - 14% from the reference (GC) ã/M value. Furthermore, better quantitative accuracy (within 2% from GC) in the SPECT ã/M value is achieved when SPECT activities are compensated for partial recovery with a phantom-based recovery coefficient of 0.85.
Conclusion: The SPECT imaging system used, together with a robust activity quantification methodology, allows an accurate estimation of time-integrated pharmacokinetic information of the 131 I-labelled sdAb in mouse kidneys. This opens the possibility to perform mouse-specific kidney-tissue dosimetry based on pharmacokinetic data acquired in vivo on the same mice used in nephrotoxicity studies.
(© 2022. The Author(s).)
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فهرسة مساهمة: Keywords: Accuracy; Activity quantification; HER2; Kidney; Micro-SPECT; Mouse-specific pharmacokinetics; Single-domain antibody fragment
تواريخ الأحداث: Date Created: 20220223 Latest Revision: 20220304
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8866625
DOI: 10.1186/s40658-022-00443-5
PMID: 35195790
قاعدة البيانات: MEDLINE
الوصف
تدمد:2197-7364
DOI:10.1186/s40658-022-00443-5