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Nuklearmedizin
DOI: 10.1055/a-2543-0723
Original Article

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

Anders Örbom
1   Section of Oncology, Lund University Department of Clinical Sciences Lund, Lund, Sweden (Ringgold ID: RIN156327)
,
Susan Evans-Axelsson
2   Section of Urological cancers, Department of Translational Medicine, Lund University Faculty of Medicine, Lund, Sweden (Ringgold ID: RIN59568)
,
Bo Jansson
3   Section of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University Faculty of Medicine, Lund, Sweden (Ringgold ID: RIN59568)
,
Oskar Vilhelmsson Timmermand
1   Section of Oncology, Lund University Department of Clinical Sciences Lund, Lund, Sweden (Ringgold ID: RIN156327)
,
Thuy A. Tran
4   Department of Radiopharmacy, Karolinska University Hospital, Stockholm, Sweden (Ringgold ID: RIN59562)
5   Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden (Ringgold ID: RIN27106)
,
Anders Bjartell
2   Section of Urological cancers, Department of Translational Medicine, Lund University Faculty of Medicine, Lund, Sweden (Ringgold ID: RIN59568)
,
Sven-Erik Strand
6   Medical Radiation Physics, Lund University Department of Clinical Sciences Lund, Lund, Sweden (Ringgold ID: RIN156327)
› Author AffiliationsSupported by: Government funding of clinical research within the national health service, Lund University, Sweden (ALF)
Supported by: Cancerfonden
Supported by: Eurostars
Supported by: Gunnar Nilssons Cancerstiftelse
Supported by: Vetenskapsrådet
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Abstract

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

Supplementary Material



Publication History

Received: 27 May 2024

Accepted after revision: 19 February 2025

Article published online:
18 March 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

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