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PSA-Targeted Alpha-...
PSA-Targeted Alpha-, Beta-, and Positron-emitting immunotheranostics in murine prostate cancer models and nonhuman primates
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- Veach, Darren R. (författare)
- Weill Cornell Medical College,Memorial Sloan-Kettering Cancer Center
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- Storey, Claire M. (författare)
- University of California, Los Angeles
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- Lückerath, Katharina (författare)
- University of California, Los Angeles
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Braun, Katharina (författare)
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Von Bodman, Christian (författare)
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- Lamminmäki, Urpo (författare)
- University of Turku
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- Kalidindi, Teja (författare)
- Memorial Sloan-Kettering Cancer Center
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- Strand, Sven Erik (författare)
- Lund University,Lunds universitet,Medicinsk strålningsfysik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Forskningsgruppen för Systemisk strålterapi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Strålterapi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medical Radiation Physics, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Systemic Radiation Therapy Group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Radiation therapy,Section I,Department of Clinical Sciences, Lund
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- Strand, Joanna (författare)
- Lund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Strålterapi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Radiation therapy,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Altai, Mohamed (författare)
- Lund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Strålterapi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Radiation therapy,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Damoiseaux, Robert (författare)
- University of California, Los Angeles
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- Zanzonico, Pat (författare)
- Memorial Sloan-Kettering Cancer Center
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- Benabdallah, Nadia (författare)
- Washington University in St. Louis
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- Pankov, Dmitry (författare)
- Memorial Sloan-Kettering Cancer Center
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- Scher, Howard I. (författare)
- Weill Cornell Medical College,Memorial Sloan-Kettering Cancer Center
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- Scardino, Peter (författare)
- Memorial Sloan-Kettering Cancer Center,Weill Cornell Medical College
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- Larson, Steven M. (författare)
- Memorial Sloan-Kettering Cancer Center,Weill Cornell Medical College
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- Lilja, Hans (författare)
- Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Clinical Chemistry, Malmö,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Memorial Sloan-Kettering Cancer Center
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- McDevitt, Michael R. (författare)
- Memorial Sloan-Kettering Cancer Center,Weill Cornell Medical College
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- Thorek, Daniel L.J. (författare)
- Washington University in St. Louis
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- Ulmert, David (författare)
- University of California, Los Angeles
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(creator_code:org_t)
- 2021
- 2021
- Engelska 11 s.
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 27:7, s. 2050-2060
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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 89Zr- or treated with 90Y- or 225Ac-labeled hu5A10; biodistribution and subcellular localization were analyzed by gamma counting, PET, autoradiography, and microscopy. Therapeutic efficacy of [225Ac]hu5A10 and [90Y]hu5A10 in LNCaP-AR tumors was assessed by tumor volume measurements, time to nadir (TTN), time to progression (TTP), and survival. Pharmacokinetics of [89Zr]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 [90Y]/[225Ac]hu5A10 effectively reduced tumor burden and prolonged survival (P ≤ 0.0054). Effects of [90Y]hu5A10 were more immediate than [225Ac]hu5A10 (TTN, P < 0.0001) but less sustained (TTP, P < 0.0001). Complete responses were observed in 7 of 18 [225Ac]hu5A10 and 1 of 9 mice [90Y]hu5A10. Pharmacokinetics of [89Zr]hu5A10 were consistent between NHPs and comparable with those in mice. [89Zr]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 PSAexpressing tissue. Our data support the clinical translation of radiolabeled hu5A10 for treating prostate cancer.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Veach, Darren R.
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Storey, Claire M ...
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Lückerath, Katha ...
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Braun, Katharina
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Von Bodman, Chri ...
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Lamminmäki, Urpo
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visa fler...
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Kalidindi, Teja
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Strand, Sven Eri ...
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Strand, Joanna
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Altai, Mohamed
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Damoiseaux, Robe ...
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Zanzonico, Pat
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Benabdallah, Nad ...
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Pankov, Dmitry
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Scher, Howard I.
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Scardino, Peter
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Larson, Steven M ...
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Lilja, Hans
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McDevitt, Michae ...
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Thorek, Daniel L ...
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Ulmert, David
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
- Artiklar i publikationen
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Clinical Cancer ...
- Av lärosätet
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Lunds universitet