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Intratumoral distribution and pharmacokinetics of the radiolabeled ICAM-1 targeting monoclonal antibody R6.5 in a prostate cancer mouse model

Örbom, Anders LU orcid ; Evans-Axelsson, Susan LU orcid ; Jansson, Bo LU ; Vilhelmsson Timmermand, Oskar LU orcid ; Tran, Thuy A LU ; Bjartell, Anders LU and Strand, Sven-Erik LU (2025) In Nuklearmedizin
Abstract

Despite new therapies, castration-resistant prostate cancer (CRPC) is still incurable. Intercellular Adhesion Molecule 1 (ICAM-1) is a well-characterized cell surface protein involved in prostate cancer pathogenesis, differentially expressed during transition from hormone-sensitive to CRPC. This study aimed to investigate ICAM-1 as a target for imaging and radioimmunotherapy of CRPC.Anti-ICAM-1 antibody R6.5 was labeled with 111In or 177Lu, and a non-specific antibody with 177Lu. In vitro uptake of R6.5 was tested in PC-3 prostate cancer cells. Biodistribution studies, SPECT/CT imaging, and autoradiography were performed in a PC-3 xenograft model.In vitro uptake of R6.5 ([177Lu]Lu-R6.5) increased during 6 h of incubation. The uptake was... (More)

Despite new therapies, castration-resistant prostate cancer (CRPC) is still incurable. Intercellular Adhesion Molecule 1 (ICAM-1) is a well-characterized cell surface protein involved in prostate cancer pathogenesis, differentially expressed during transition from hormone-sensitive to CRPC. This study aimed to investigate ICAM-1 as a target for imaging and radioimmunotherapy of CRPC.Anti-ICAM-1 antibody R6.5 was labeled with 111In or 177Lu, and a non-specific antibody with 177Lu. In vitro uptake of R6.5 was tested in PC-3 prostate cancer cells. Biodistribution studies, SPECT/CT imaging, and autoradiography were performed in a PC-3 xenograft model.In vitro uptake of R6.5 ([177Lu]Lu-R6.5) increased during 6 h of incubation. The uptake was higher at lower mAb concentration and could be blocked by 500 nM of unlabeled R6.5. In vivo and ex vivo biodistribution showed that [111In]In-R6.5 and [177Lu]Lu-R6.5 targeted the xenograft tumors better than the control Ab, however [111In]In-R6.5 had better tumor uptake than [177Lu]Lu-R6.5, probably due to less aggressive conjugation with chelator and smaller tumor sizes. From 24 h post-injection, the tumors in mice injected with [111In]In-R6.5 and [177Lu]Lu-R6.5 were visible on SPECT, optimal contrast at 48 h. Uptake was low in normal organs except the spleen and liver for all mAbs. Autoradiography showed [111In]In-R6.5 and [177Lu]Lu-R6.5 accumulated along the edges of viable tumor. The control Ab tended to accumulate in partly necrotic areas.This study demonstrates ICAM-1 as a potential target for theragnostics in CRPC.

(Less)
Abstract (Swedish)
Aim
Despite new therapies, castration-resistant prostate cancer (CRPC) is still incurable. Intercellular Adhesion Molecule 1 (ICAM-1) is a well-characterized cell surface protein involved in prostate cancer pathogenesis, differentially expressed during transition from hormone-sensitive to CRPC. This study aimed to investigate ICAM-1 as a target for imaging and radioimmunotherapy of CRPC.

Methods
Anti-ICAM-1 antibody R6.5 was labeled with 111In or 177Lu, and a non-specific antibody with 177Lu. In vitro uptake of R6.5 was tested in PC-3 prostate cancer cells. Biodistribution studies, SPECT/CT imaging, and autoradiography were performed in a PC-3 xenograft model.

Results
In vitro uptake of R6.5 ([177Lu]Lu-R6.5)... (More)
Aim
Despite new therapies, castration-resistant prostate cancer (CRPC) is still incurable. Intercellular Adhesion Molecule 1 (ICAM-1) is a well-characterized cell surface protein involved in prostate cancer pathogenesis, differentially expressed during transition from hormone-sensitive to CRPC. This study aimed to investigate ICAM-1 as a target for imaging and radioimmunotherapy of CRPC.

Methods
Anti-ICAM-1 antibody R6.5 was labeled with 111In or 177Lu, and a non-specific antibody with 177Lu. In vitro uptake of R6.5 was tested in PC-3 prostate cancer cells. Biodistribution studies, SPECT/CT imaging, and autoradiography were performed in a PC-3 xenograft model.

Results
In vitro uptake of R6.5 ([177Lu]Lu-R6.5) increased during 6 h of incubation. The uptake was higher at lower mAb concentration and could be blocked by 500 nM of unlabeled R6.5. In vivo and ex vivo biodistribution showed that [111In]In-R6.5 and [177Lu]Lu-R6.5 targeted the xenograft tumors better than the control Ab, however [111In]In-R6.5 had better tumor uptake than [177Lu]Lu-R6.5, probably due to less aggressive conjugation with chelator and smaller tumor sizes. From 24 h post-injection, the tumors in mice injected with [111In]In-R6.5 and [177Lu]Lu-R6.5 were visible on SPECT, optimal contrast at 48 h. Uptake was low in normal organs except the spleen and liver for all mAbs. Autoradiography showed [111In]In-R6.5 and [177Lu]Lu-R6.5 accumulated along the edges of viable tumor. The control Ab tended to accumulate in partly necrotic areas.

Conclusion
This study demonstrates ICAM-1 as a potential target for theragnostics in CRPC.

Keywords
ICAM-1 - CD54 - R6.5 - prostate cancer - radionuclide therapy (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Nuklearmedizin
publisher
Georg Thieme Verlag
external identifiers
  • scopus:105000254564
  • pmid:40101791
ISSN
0029-5566
DOI
10.1055/a-2543-0723
language
English
LU publication?
yes
additional info
Thieme. All rights reserved.
id
1e8bbfcf-c2f1-43ad-aa45-94853f11d323
date added to LUP
2025-03-20 16:10:26
date last changed
2025-07-05 07:04:23
@article{1e8bbfcf-c2f1-43ad-aa45-94853f11d323,
  abstract     = {{<p>Despite new therapies, castration-resistant prostate cancer (CRPC) is still incurable. Intercellular Adhesion Molecule 1 (ICAM-1) is a well-characterized cell surface protein involved in prostate cancer pathogenesis, differentially expressed during transition from hormone-sensitive to CRPC. This study aimed to investigate ICAM-1 as a target for imaging and radioimmunotherapy of CRPC.Anti-ICAM-1 antibody R6.5 was labeled with 111In or 177Lu, and a non-specific antibody with 177Lu. In vitro uptake of R6.5 was tested in PC-3 prostate cancer cells. Biodistribution studies, SPECT/CT imaging, and autoradiography were performed in a PC-3 xenograft model.In vitro uptake of R6.5 ([177Lu]Lu-R6.5) increased during 6 h of incubation. The uptake was higher at lower mAb concentration and could be blocked by 500 nM of unlabeled R6.5. In vivo and ex vivo biodistribution showed that [111In]In-R6.5 and [177Lu]Lu-R6.5 targeted the xenograft tumors better than the control Ab, however [111In]In-R6.5 had better tumor uptake than [177Lu]Lu-R6.5, probably due to less aggressive conjugation with chelator and smaller tumor sizes. From 24 h post-injection, the tumors in mice injected with [111In]In-R6.5 and [177Lu]Lu-R6.5 were visible on SPECT, optimal contrast at 48 h. Uptake was low in normal organs except the spleen and liver for all mAbs. Autoradiography showed [111In]In-R6.5 and [177Lu]Lu-R6.5 accumulated along the edges of viable tumor. The control Ab tended to accumulate in partly necrotic areas.This study demonstrates ICAM-1 as a potential target for theragnostics in CRPC.</p>}},
  author       = {{Örbom, Anders and Evans-Axelsson, Susan and Jansson, Bo and Vilhelmsson Timmermand, Oskar and Tran, Thuy A and Bjartell, Anders and Strand, Sven-Erik}},
  issn         = {{0029-5566}},
  language     = {{eng}},
  month        = {{03}},
  publisher    = {{Georg Thieme Verlag}},
  series       = {{Nuklearmedizin}},
  title        = {{Intratumoral distribution and pharmacokinetics of the radiolabeled ICAM-1 targeting monoclonal antibody R6.5 in a prostate cancer mouse model}},
  url          = {{http://dx.doi.org/10.1055/a-2543-0723}},
  doi          = {{10.1055/a-2543-0723}},
  year         = {{2025}},
}