ArticleMolecular cancer therapeutics2025
Evaluation of VLA-4 (Integrin α4β1) as a Shared Target for Radiopharmaceutical Therapy across Solid Tumors.
Article in Molecular cancer therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- A radiopharmaceutical enhances CAR T cells against radio-sensitive and radio-resistant neuroblastoma by tumor sensitization and TME remodeling.Cell reports. Medicine · 2026Article
- Review
- Pharmacokinetics study of FT-FAPI, a novel multi-nuclide label-able FAP targeting tracer, in mice and healthy volunteers.European journal of nuclear medicine and molecular imaging · 2025Article
- Understanding Merkel Cell Carcinoma: Pathogenic Signaling, Extracellular Matrix Dynamics, and Novel Treatment Approaches.Cancers · 2025Review
- Immune microenvironment regulation and clinical immunotherapy strategies of metastatic liver cancer.Frontiers in immunology · 2025Review
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Authors and funding
21 authors.
Funding
Abstract
Radiopharmaceutical therapy (RPT) is a promising approach to treating solid tumors, but therapeutic advances are impeded by the lack of broadly expressed targets and shared molecular vulnerability across different tumor types. Here, we evaluate VLA-4 (integrin α4β1) as a potential target for RPT in solid tumors and use radiolabeled copper-64 ([64Cu]Cu-) and copper-67 ([67Cu]Cu-CB-TE1A1P-PEG4-LLP2A) LLP2A, a peptidomimetic ligand of VLA-4, for preclinical imaging and RPT testing. Expression of ITGA4, the gene encoding the alpha 4 subunit (CD49d) of VLA-4, was evaluated in a variety of cancer tissues from publicly available datasets. VLA-4 protein expression was determined by flow cytometry in 22 different human and murine cancer cell lines. We used orthotopic syngeneic (i.e., B16-F10, B78, 4T1, GL261, TH-MYCN, and E2A-PBX1) and human (i.e., SK-MEL-37, 143B, and IMR-5) cancer models for in vivo PET/CT imaging and biodistribution studies. Selected models were used for dosimetry calculations with [64Cu]Cu-LLP2A. To assess in vivo tolerability and efficacy, we performed studies of [67Cu]Cu-LLP2A in tumor-free and B16-F10-bearing C57BL/6J mice (activity range, 0-74 MBq [0-2 mCi]), respectively. We found ITGA4 is overexpressed in hematological malignancies and a variety of solid tumors compared with healthy tissue. VLA-4 was expressed at medium to high levels in 17/22 (77%), at low levels in 4/22 (18%), and negative in 1/22 (5%) tested cell lines. PET/CT imaging with [64Cu]Cu-LLP2A showed tracer uptake in tumors and on-target off-tumor uptake in lymphoid tissues. [67Cu]Cu-LLP2A administered at an activity range of 37 to 74 MBq (1-2 mCi) was tolerated and did not cause long-term hematological or tissue toxicity, except for thymic atrophy. We observed tumor dose response to the activity administered to mice with B16-F10 melanoma. In summary, VLA-4 is broadly expressed across a variety of different cancer tissues and preclinical cancer cell lines, making it a promising target for [67Cu]Cu-LLP2A RPT. With proven on-target on-tumor effect, acceptable toxicity profile, and favorable dosimetry in preclinical models, further investigation of [67Cu]Cu-LLP2A as an RPT agent is warranted.
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