دورية أكاديمية
أعرض في EDS

Targeting Breast Cancer Using 177 Lu-Labeled Trastuzumab and Trastuzumab Fragment : First-in-Human Clinical Experience.

التفاصيل البيبلوغرافية
العنوان: Targeting Breast Cancer Using 177 Lu-Labeled Trastuzumab and Trastuzumab Fragment : First-in-Human Clinical Experience.
المؤلفون: Rathore Y; From the Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh., Lakhanpal T; From the Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh., Chakraborty S, Chakravarty R, Mittal BR; From the Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh., Irrinki RNS; Department of General Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India., Laroiya I; Department of General Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India., Kaur K; From the Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh., Shukla J; From the Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh.
المصدر: Clinical nuclear medicine [Clin Nucl Med] 2024 Jun 01; Vol. 49 (6), pp. e258-e265. Date of Electronic Publication: 2024 Apr 05.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Lippincott Country of Publication: United States NLM ID: 7611109 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1536-0229 (Electronic) Linking ISSN: 03639762 NLM ISO Abbreviation: Clin Nucl Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Philadelphia, Lippincott.
مواضيع طبية MeSH: Trastuzumab*/pharmacology , Trastuzumab*/pharmacokinetics , Trastuzumab*/chemistry , Breast Neoplasms*/diagnostic imaging , Breast Neoplasms*/drug therapy , Lutetium* , Isotope Labeling* , Immunoglobulin Fab Fragments* , Radioisotopes*, Humans ; Female
مستخلص: Purpose: A monoclonal antibody, trastuzumab, is used for immunotherapy for HER2-expressing breast cancers. Large-sized antibodies demonstrate hepatobiliary clearance and slower pharmacokinetics. A trastuzumab fragment (Fab; 45 kDa) has been generated for theranostic use.
Patients and Methods: Fab was generated by papain digestion. Trastuzumab and Fab have been radiolabelled with 177 Lu after being conjugated with a bifunctional chelating. The affinity and target specificity were studied in vitro. The first-in-human study was performed.
Results: The bifunctional chelating agent conjugation of 1-2 molecules with trastuzumab and Fab was detected at the molar ratio 1:10 in bicarbonate buffer (0.5 M, pH 8) at 37°-40°C. However, 2-3 molecules of bifunctional chelating agent were conjugated when DMSO in PBS (0.1 M, pH 7) was used as a conjugation buffer at a molar ratio of 1:10. The radiolabelling yield of DOTA-conjugated Fab and trastuzumab at pH 5, 45°C to 50°C, with incubation time 2.5-3 hours was 80% and 41.67%, respectively. However, with DOTAGA-conjugated trastuzumab and Fab, the maximum radiolabelling yield at pH 5.5, 37°C, and at 2.5-3 hours was 80.83% and 83%, respectively. The calculated K d of DOTAGA Fab and trastuzumab with HER2-positive SKBR3 cells was 6.85 ± 0.24 × 10 -8 M and 1.71 ± 0.10 × 10 -8 M, respectively. DOTAGA-Fab and trastuzumab showed better radiolabelling yield at mild reaction conditions.177 Lu-DOTAGA-Fab demonstrated higher lesion uptake and lower liver retention as compared with 177 Lu-DOTAGA-trastuzumab. However, 177 Lu-DOTAGA-Fab as compared with 177 Lu-DOTAGA-trastuzumab showed a relatively early washout (5 days) from the lesion.
Conclusions: 177 Lu-DOTAGA-Fab and trastuzumab are suitable for targeting the HER2 receptors.
Competing Interests: Conflicts of interest and sources of funding: none declared.
(Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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المشرفين على المادة: P188ANX8CK (Trastuzumab)
5H0DOZ21UJ (Lutetium)
0 (Immunoglobulin Fab Fragments)
0 (Radioisotopes)
BRH40Y9V1Q (Lutetium-177)
تواريخ الأحداث: Date Created: 20240405 Date Completed: 20240505 Latest Revision: 20240505
رمز التحديث: 20240505
DOI: 10.1097/RLU.0000000000005208
PMID: 38579266
قاعدة البيانات: MEDLINE
الوصف
تدمد:1536-0229
DOI:10.1097/RLU.0000000000005208