{"doi":"10.3390/ph18081122","title":"LAMP1 as a Target for PET Imaging in Adenocarcinoma Xenograft Models","abstract":"Background: Lysosomal-associated membrane protein 1 (LAMP1), typically localized to the lysosomal membrane, is increasingly implicated as a marker of cancer aggressiveness and metastasis when expressed on the cell surface. This study aimed to develop a LAMP1-targeted antibody-based PET tracer and assess its efficacy in mouse models of human breast and colon adenocarcinoma. Methods: To determine the source of LAMP1 expression, we utilized human single-cell RNA sequencing and spatial transcriptomics, complemented by in-house flow cytometry on xenografted mouse models. Tissue microarrays of multiple epithelial cancers and normal tissue were stained for LAMP-1, and staining was quantified. An anti-LAMP1 monoclonal antibody was conjugated with desferrioxamine (DFO) and labeled with zirconium-89 (89Zr). Human triple-negative breast cancer (MDA-MB-231) and colon cancer (Caco-2) cell lines were implanted in nude mice. PET/CT imaging was conducted at 24, 72, and 168 h post-intravenous injection of 89Zr-DFO-anti-LAMP1 and 89Zr-DFO-IgG (negative control), followed by organ-specific biodistribution analyses at the final imaging time point. Results: Integrated single-cell and spatial RNA sequencing demonstrated that LAMP1 expression was localized to myeloid-derived suppressor cells (MDSCs) and cancer-associated fibroblasts (CAFs) in addition to the cancer cells. Tissue microarray showed significantly higher staining for LAMP-1 in tumor tissue compared to normal tissue (3986 ± 2635 vs. 1299 ± 1291, p < 0.001). Additionally, xenograft models showed a significantly higher contribution of cancer cells than the immune cells to cell surface LAMP1 expression. In vivo, PET imaging with 89Zr-DFO-anti-LAMP1 PET/CT revealed detectable tumor uptake as early as 24 h post-injection. The 89Zr-DFO-anti-LAMP1 tracer demonstrated significantly higher uptake than the control 89Zr-DFO-IgG in both models across all time points (MDA-MB-231 SUVmax at 168 h: 12.9 ± 5.7 vs. 4.4 ± 2.4, p = 0.003; Caco-2 SUVmax at 168 h: 8.53 ± 3.03 vs. 3.38 ± 1.25, p < 0.01). Conclusions: Imaging of cell surface LAMP-1 in breast and colon adenocarcinoma is feasible by immuno-PET. LAMP-1 imaging can be expanded to adenocarcinomas of other origins, such as prostate and pancreas.","journal":"Pharmaceuticals","year":2025,"id":545595,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9378,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":48832,"name":"Arvin Haj‐Mirzaian","orcid":"0000-0001-8977-6865","position":1,"is_corresponding":false},{"id":1436873,"name":"Lital Ben-Naim","orcid":null,"position":2,"is_corresponding":false},{"id":962565,"name":"Shadi A. Esfahani","orcid":"0000-0002-6077-4580","position":3,"is_corresponding":false},{"id":1157472,"name":"Asier Marcos-Vidal","orcid":"0000-0001-9601-2433","position":4,"is_corresponding":false},{"id":424762,"name":"Umar Mahmood","orcid":"0000-0001-7414-6123","position":5,"is_corresponding":false},{"id":424761,"name":"Pedram Heidari","orcid":"0000-0001-6383-465X","position":6,"is_corresponding":false},{"id":424759,"name":"Bahar Ataeinia","orcid":"0000-0002-6739-6877","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T02:53:23.001995Z","pmid":"40872517","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}