دورية أكاديمية
أعرض في EDS

Radiolabeled antibodies in prostate cancer: a case study showing the effect of host immunity on antibody bio-distribution.

التفاصيل البيبلوغرافية
العنوان: Radiolabeled antibodies in prostate cancer: a case study showing the effect of host immunity on antibody bio-distribution.
المؤلفون: Vilhelmsson-Timmermand O; Department of Medical Radiation Physics, Lund University, Lund, Sweden., Santos E; Department of Radiology (Nuclear Medicine Service), Memorial Sloan-Kettering Cancer Center, New York, NY, USA., Thorek DL; Department of Radiology and Radiological Sciences, Division of Nuclear Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Evans-Axelsson S; Department of Clinical Sciences, Division of Urological Cancers, Lund University, Malmö, Sweden., Bjartell A; Department of Clinical Sciences, Division of Urological Cancers, Lund University, Malmö, Sweden., Lilja H; Department of Surgery (Urology), Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Departments of Laboratory Medicine and Medicine (GU Oncology), Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom; Department of Laboratory Medicine, Lund University, Malmö, Sweden., Larson SM; Department of Radiology (Nuclear Medicine Service), Memorial Sloan-Kettering Cancer Center, New York, NY, USA., Strand SE; Department of Medical Radiation Physics, Lund University, Lund, Sweden., Tran TA; Department of Medical Radiation Physics, Lund University, Lund, Sweden; Lund University Bioimaging Center, Lund University, Lund, Sweden., Ulmert D; Department of Surgery (Urology), Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Department of Clinical Sciences, Division of Urological Research, Lund University, Malmö, Sweden. Electronic address: ulmerth@mskcc.org.
المصدر: Nuclear medicine and biology [Nucl Med Biol] 2015 Apr; Vol. 42 (4), pp. 375-80. Date of Electronic Publication: 2014 Dec 23.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 9304420 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-9614 (Electronic) Linking ISSN: 09698051 NLM ISO Abbreviation: Nucl Med Biol Subsets: MEDLINE
أسماء مطبوعة: Publication: : Philadelphia : Elsevier
Original Publication: Oxford ; New York : Pergamon, 1993-
مواضيع طبية MeSH: Immunoconjugates/*pharmacokinetics , Immunoglobulin G/*chemistry , Prostatic Neoplasms/*immunology , Prostatic Neoplasms/*metabolism, Animals ; Cell Line, Tumor ; Cell Transformation, Neoplastic ; Humans ; Immunocompetence ; Indium Radioisotopes ; Isotope Labeling ; Male ; Mice ; Pentetic Acid/chemistry ; Prostatic Neoplasms/pathology ; Tissue Distribution
مستخلص: Objectives: Human tumors xenografted in immunodeficient mice are crucial models in nuclear medicine to evaluate the effectiveness of candidate diagnostic and therapeutic compounds. However, little attention has been focused on the biological profile of the host model and its potential effects on the bio-distribution and tumor targeting of the tracer compound under study. We specifically investigated the dissimilarity in bio-distribution of (111)In-DTPA-5A10, which targets free prostate specific antigen (fPSA), in two animal models.
Methods: In vivo bio-distribution studies of (111)In-DTPA-5A10 were performed in immunodeficient BALB/c-nu or NMRI-nu mice with subcutaneous (s.c.) LNCaP tumors. Targeting-specificity of the tracer was assessed by quantifying the uptake in (a) mice with s.c. xenografts of PSA-negative DU145 cells as well as (b) BALB/c-nu or NMRI-nu mice co-injected with an excess of non-labeled 5A10. Finally, the effect of neonatal Fc-receptor (FcRn) inhibition on the bio-distribution of the conjugate was studied by saturating FcRn-binding capacity with nonspecific IgG1.
Results: The inherent biological attributes of the mouse model substantially influenced the bio-distribution and pharmacokinetics of (111)In-DTPA-5A10. With LNCaP xenografts in BALB/c-nu mice (with intact B and NK cells but with deficient T cells) versus NMRI-nu mice (with intact B cells, increased NK cells and absent T cells), we observed a significantly higher hepatic accumulation (26 ± 3.9 versus 3.5 ± 0.4%IA/g respectively), and concomitantly lower tumor uptake (25 ± 11 versus 52 ± 10%IA/g respectively) in BALB/c-nu mice. Inhibiting FcRn by administration of nonspecific IgG1 just prior to (111)In-DTPA-5A10 did not change tumor accumulation significantly.
Conclusions: We demonstrated that the choice of immunodeficient mouse model importantly influence the bio-distribution of (111)In-DTPA-5A10. This study further highlighted important considerations in the evaluation of preclinical tracers, with respect to gaining information on their performance in the translational setting. Investigators utilizing xenograft models need to assess not only radiolabeling strategies, but also the host immunological status.
(Copyright © 2014 Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: P30 CA008748 United States CA NCI NIH HHS; P50 CA086438 United States CA NCI NIH HHS; P50 CA092629 United States CA NCI NIH HHS; S10 RR020892 United States RR NCRR NIH HHS
فهرسة مساهمة: Keywords: Antibodies; Biodistribution; Host-immunity; Pre-clinical studies; fPSA-targeting
المشرفين على المادة: 0 (Immunoconjugates)
0 (Immunoglobulin G)
0 (Indium Radioisotopes)
7A314HQM0I (Pentetic Acid)
تواريخ الأحداث: Date Created: 20150112 Date Completed: 20160209 Latest Revision: 20181113
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC4472383
DOI: 10.1016/j.nucmedbio.2014.12.012
PMID: 25577038
قاعدة البيانات: MEDLINE
الوصف
تدمد:1872-9614
DOI:10.1016/j.nucmedbio.2014.12.012