دورية أكاديمية
PSA-Targeted Alpha-, Beta-, and Positron-Emitting Immunotheranostics in Murine Prostate Cancer Models and Nonhuman Primates.
| العنوان: | PSA-Targeted Alpha-, Beta-, and Positron-Emitting Immunotheranostics in Murine Prostate Cancer Models and Nonhuman Primates. |
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| المؤلفون: | Veach DR; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.; Department of Radiology, Weill Cornell Medical College, New York, New York., Storey CM; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California., Lückerath K; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California.; Ahmanson Translational Imaging Division, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.; Department of Urology, David Geffen School of Medicine, Institute of Urologic Oncology, University of California, Los Angeles, Los Angeles, California.; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California., Braun K; Department of Urology, Marien Hospital Herne, Ruhr-University Bochum, Herne, Germany., von Bodman C; Uroviva - Specialized Clinic for Urology, Bülach, Switzerland., Lamminmäki U; Department of Biochemistry, University of Turku, Turku, Finland., Kalidindi T; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York., Strand SE; Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Lund, Sweden., Strand J; Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Lund, Sweden., Altai M; Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Lund, Sweden., Damoiseaux R; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California., Zanzonico P; Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York., Benabdallah N; Department of Radiology, Washington University School of Medicine, St. Louis, Missouri., Pankov D; Immunology Program, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York., Scher HI; Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Department of Medicine, Weill Cornell Medical College, New York, New York., Scardino P; Department of Medicine, Weill Cornell Medical College, New York, New York.; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Larson SM; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.; Department of Radiology, Weill Cornell Medical College, New York, New York., Lilja H; Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.; Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Department of Translational Medicine, Lund University, Malmö, Sweden., McDevitt MR; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.; Department of Radiology, Weill Cornell Medical College, New York, New York., Thorek DLJ; Department of Radiology, Washington University School of Medicine, St. Louis, Missouri.; Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, Missouri., Ulmert D; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California. hdsulmert@gmail.com.; Ahmanson Translational Imaging Division, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.; Department of Urology, David Geffen School of Medicine, Institute of Urologic Oncology, University of California, Los Angeles, Los Angeles, California.; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, California. |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2021 Apr 01; Vol. 27 (7), pp. 2050-2060. Date of Electronic Publication: 2021 Jan 13. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Denville, NJ : The Association, c1995- |
| مواضيع طبية MeSH: | Alpha Particles/*therapeutic use , Beta Particles/*therapeutic use , Electrons/*therapeutic use , Prostate-Specific Antigen/*immunology , Prostatic Neoplasms/*radiotherapy , Radioimmunotherapy/*methods, Animals ; Disease Models, Animal ; Linear Energy Transfer ; Macaca fascicularis ; Male ; Mice ; Mice, Inbred BALB C ; Positron-Emission Tomography ; Prostate-Specific Antigen/metabolism ; Receptors, Androgen/physiology ; Tissue Distribution |
| مستخلص: | Purpose: Most patients with prostate cancer treated with androgen receptor (AR) signaling inhibitors develop therapeutic resistance due to restoration of AR functionality. Thus, there is a critical need for novel treatment approaches. Here we investigate the theranostic potential of hu5A10, a humanized mAb specifically targeting free PSA ( KLK3 ). Experimental Design: LNCaP-AR (LNCaP with overexpression of wildtype AR) xenografts (NSG mice) and KLK3 _Hi- Myc transgenic mice were imaged with 89 Zr- or treated with 90 Y- or 225 Ac-labeled hu5A10; biodistribution and subcellular localization were analyzed by gamma counting, PET, autoradiography, and microscopy. Therapeutic efficacy of [ 225 Ac]hu5A10 and [ 90 Y]hu5A10 in LNCaP-AR tumors was assessed by tumor volume measurements, time to nadir (TTN), time to progression (TTP), and survival. Pharmacokinetics of [ 89 Zr]hu5A10 in nonhuman primates (NHP) were determined using PET. Results: Biodistribution of radiolabeled hu5A10 constructs was comparable in different mouse models. Specific tumor uptake increased over time and correlated with PSA expression. Treatment with [ 90 Y]/[ 225 Ac]hu5A10 effectively reduced tumor burden and prolonged survival ( P ≤ 0.0054). Effects of [ 90 Y]hu5A10 were more immediate than [ 225 Ac]hu5A10 (TTN, P < 0.0001) but less sustained (TTP, P < 0.0001). Complete responses were observed in 7 of 18 [ 225 Ac]hu5A10 and 1 of 9 mice [ 90 Y]hu5A10. Pharmacokinetics of [ 89 Zr]hu5A10 were consistent between NHPs and comparable with those in mice. [ 89 Zr]hu5A10-PET visualized the NHP-prostate over the 2-week observation period. Conclusions: We present a complete preclinical evaluation of radiolabeled hu5A10 in mouse prostate cancer models and NHPs, and establish hu5A10 as a new theranostic agent that allows highly specific and effective downstream targeting of AR in PSA-expressing tissue. Our data support the clinical translation of radiolabeled hu5A10 for treating prostate cancer. (©2021 American Association for Cancer Research.) |
| التعليقات: | Comment in: Nat Rev Urol. 2021 Mar;18(3):131. (PMID: 33564167) |
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| معلومات مُعتمدة: | R01 CA201035 United States CA NCI NIH HHS; R01 CA055349 United States CA NCI NIH HHS; P50 CA086438 United States CA NCI NIH HHS; F31 CA167863 United States CA NCI NIH HHS; R01 CA166078 United States CA NCI NIH HHS; S10 RR020892 United States RR NCRR NIH HHS; S10 RR028889 United States RR NCRR NIH HHS; R01 CA229893 United States CA NCI NIH HHS; P01 CA033049 United States CA NCI NIH HHS; P50 CA092629 United States CA NCI NIH HHS; P30 CA008748 United States CA NCI NIH HHS; R01 CA240711 United States CA NCI NIH HHS; P50 CA092131 United States CA NCI NIH HHS; P30 CA016042 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (Receptors, Androgen) EC 3.4.21.77 (Prostate-Specific Antigen) |
| تواريخ الأحداث: | Date Created: 20210114 Date Completed: 20220309 Latest Revision: 20220309 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC8278668 |
| DOI: | 10.1158/1078-0432.CCR-20-3614 |
| PMID: | 33441295 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1557-3265 |
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| DOI: | 10.1158/1078-0432.CCR-20-3614 |