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

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Nuklearmedizin. Nuclear Medicine
|March 18, 2025
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Summary

Intercellular Adhesion Molecule 1 (ICAM-1) shows promise as a target for castration-resistant prostate cancer (CRPC) theragnostics. Radiolabeled antibodies targeting ICAM-1 effectively visualized tumors in preclinical models, indicating potential for imaging and therapy.

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Area of Science:

  • Nuclear Medicine
  • Oncology
  • Immunotherapy

Background:

  • Castration-resistant prostate cancer (CRPC) remains incurable despite new treatments.
  • Intercellular Adhesion Molecule 1 (ICAM-1) is implicated in prostate cancer progression and is differentially expressed in CRPC.
  • ICAM-1 is a potential target for novel diagnostic and therapeutic strategies.

Purpose of the Study:

  • To evaluate Intercellular Adhesion Molecule 1 (ICAM-1) as a theragnostic target for CRPC.
  • To assess the efficacy of anti-ICAM-1 antibody R6.5 labeled with radionuclides for imaging and radioimmunotherapy.

Main Methods:

  • Anti-ICAM-1 antibody R6.5 was labeled with Indium-111 (111In) or Lutetium-177 (177Lu).
  • In vitro cell uptake studies were conducted using PC-3 prostate cancer cells.
  • In vivo biodistribution, SPECT/CT imaging, and autoradiography were performed in a PC-3 xenograft mouse model.

Main Results:

  • Radiolabeled R6.5 demonstrated specific uptake in PC-3 cells in vitro.
  • [111In]In-R6.5 and [177Lu]Lu-R6.5 showed preferential tumor targeting in vivo compared to a control antibody.
  • SPECT/CT imaging visualized tumors from 24 hours post-injection, with optimal contrast at 48 hours.
  • Autoradiography revealed accumulation of radiolabeled R6.5 along the edges of viable tumor tissue.

Conclusions:

  • ICAM-1 is a viable target for theragnostic applications in CRPC.
  • Radiolabeled anti-ICAM-1 antibodies show potential for both imaging and targeted radioimmunotherapy of CRPC.
  • Further studies are warranted to explore the therapeutic efficacy of this approach.