{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:17:00Z","timestamp":1788585420767,"version":"build-2803163510"},"reference-count":43,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,27]],"date-time":"2025-07-27T00:00:00Z","timestamp":1753574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["K08CA249047"],"award-info":[{"award-number":["K08CA249047"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>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 \u00b1 2635 vs. 1299 \u00b1 1291, p &lt; 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 \u00b1 5.7 vs. 4.4 \u00b1 2.4, p = 0.003; Caco-2 SUVmax at 168 h: 8.53 \u00b1 3.03 vs. 3.38 \u00b1 1.25, p &lt; 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.<\/jats:p>","DOI":"10.3390\/ph18081122","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T07:57:24Z","timestamp":1753689444000},"page":"1122","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["LAMP1 as a Target for PET Imaging in Adenocarcinoma Xenograft Models"],"prefix":"10.3390","volume":"18","author":[{"given":"Bahar","family":"Ataeinia","sequence":"first","affiliation":[{"name":"Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"},{"name":"Center for Precision Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8977-6865","authenticated-orcid":false,"given":"Arvin","family":"Haj-Mirzaian","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"},{"name":"Center for Precision Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lital","family":"Ben-Naim","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"},{"name":"Center for Precision Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shadi A.","family":"Esfahani","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"},{"name":"Center for Precision Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asier","family":"Marcos Vidal","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"},{"name":"Center for Precision Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7414-6123","authenticated-orcid":false,"given":"Umar","family":"Mahmood","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"},{"name":"Center for Precision Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6383-465X","authenticated-orcid":false,"given":"Pedram","family":"Heidari","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"},{"name":"Center for Precision Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,27]]},"reference":[{"key":"ref_1","first-page":"394","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","first-page":"7","article-title":"Cancer statistics, 2021","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100414","DOI":"10.1016\/j.ejro.2022.100414","article-title":"Teaching cancer imaging in the era of precision medicine: Looking at the big picture","volume":"9","author":"Chin","year":"2022","journal-title":"Eur. J. Radiol. Open"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/s41568-023-00576-4","article-title":"Advances in PET imaging of cancer","volume":"23","author":"Schwenck","year":"2023","journal-title":"Nat. Rev. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.2967\/jnumed.111.089771","article-title":"Immuno-PET of cancer: A revival of antibody imaging","volume":"52","author":"Boerman","year":"2011","journal-title":"J. Nucl. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"647","DOI":"10.2174\/0929867327666200128102958","article-title":"Advances in Immuno-PET for the Detection of Cancer and Assessment of Response to Therapy","volume":"28","author":"Alauddin","year":"2021","journal-title":"Curr. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e2347","DOI":"10.1038\/cddis.2016.243","article-title":"Fucosylation of LAMP-1 and LAMP-2 by FUT1 correlates with lysosomal positioning and autophagic flux of breast cancer cells","volume":"7","author":"Tan","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_8","first-page":"9104","article-title":"High expression of LAMP1 as a prognostic marker in patients with epithelial ovarian cancer","volume":"10","author":"Xu","year":"2017","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Alessandrini, F., Pezz\u00e8, L., and Ciribilli, Y. (2017). LAMPs: Shedding light on cancer biology. Seminars in Oncology, W. B. Saunders.","DOI":"10.1053\/j.seminoncol.2017.10.013"},{"key":"ref_10","first-page":"1294","article-title":"Expression of the lysosomal-associated membrane protein-1 (LAMP-1) in astrocytomas","volume":"6","author":"Jensen","year":"2013","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4729","DOI":"10.3892\/ol.2017.6757","article-title":"LAMP1 expression is associated with poor prognosis in breast cancer","volume":"14","author":"Wang","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1186\/s13046-019-1278-9","article-title":"UBL4A inhibits autophagy-mediated proliferation and metastasis of pancreatic ductal adenocarcinoma via targeting LAMP1","volume":"38","author":"Chen","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1007\/s00432-015-1917-2","article-title":"Role of tumor cell surface lysosome-associated membrane protein-1 (LAMP1) and its associated carbohydrates in lung metastasis","volume":"141","author":"Agarwal","year":"2015","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e12146","DOI":"10.1002\/jev2.12146","article-title":"Hypoxia-stimulated ATM activation regulates autophagy-associated exosome release from cancer-associated fibroblasts to promote cancer cell invasion","volume":"10","author":"Xi","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1038\/s41591-022-02084-8","article-title":"Whole-body CD8+ T cell visualization before and during cancer immunotherapy: A phase 1\/2 trial","volume":"28","author":"Giesen","year":"2022","journal-title":"Nat. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/s41586-024-08441-6","article-title":"CD45-PET is a robust, non-invasive tool for imaging inflammation","volume":"639","author":"Rowley","year":"2025","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s40644-024-00658-y","article-title":"Advances of radiolabeled GRPR ligands for PET\/CT imaging of cancers","volume":"24","author":"Ma","year":"2024","journal-title":"Cancer Imaging"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"801","DOI":"10.2967\/jnumed.119.227967","article-title":"68Ga-FAPI PET\/CT: Tracer uptake in 28 different kinds of cancer","volume":"60","author":"Kratochwil","year":"2019","journal-title":"J. Nucl. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e1314","DOI":"10.7717\/peerj.1314","article-title":"Autophagic flux inhibition and lysosomogenesis ensuing cellular capture and retention of the cationic drug quinacrine in murine models","volume":"3","author":"Parks","year":"2015","journal-title":"PeerJ"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1186\/s13046-019-1449-8","article-title":"Downregulation of MYO1C mediated by cepharanthine inhibits autophagosome-lysosome fusion through blockade of the F-actin network","volume":"38","author":"Zhang","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Duangkumpha, K., Stoll, T., Phetcharaburanin, J., Yongvanit, P., Thanan, R., Techasen, A., Namwat, N., Khuntikeo, N., Chamadol, N., and Roytrakul, S. (2019). Urine proteomics study reveals potential biomarkers for the differential diagnosis of cholangiocarcinoma and periductal fibrosis. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0221024"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/cdd.2013.75","article-title":"Molecular mechanisms of ATP secretion during immunogenic cell death","volume":"21","author":"Martins","year":"2014","journal-title":"Cell Death Differ."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3522","DOI":"10.1158\/0008-5472.CAN-11-2996","article-title":"Fibroblast-derived dermal matrix drives development of aggressive cutaneous squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa","volume":"72","author":"Ng","year":"2012","journal-title":"Cancer Res."},{"key":"ref_24","first-page":"6","article-title":"Autophagy and senescence in cancer therapy","volume":"229","author":"Gewirtz","year":"2014","journal-title":"J. Cell. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1242\/bio.2012547","article-title":"Evidence for lysosomal exocytosis and release of aggrecan-degrading hydrolases from hypertrophic chondrocytes, in vitro and in vivo","volume":"1","author":"Bastow","year":"2012","journal-title":"Biol. Open"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1159\/000441143","article-title":"Rapamycin promotes the autophagic degradation of oxidized low-density lipoprotein in human umbilical vein endothelial cells","volume":"52","author":"Zhang","year":"2016","journal-title":"J. Vasc. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3690","DOI":"10.1080\/15548627.2021.1891848","article-title":"Mouse models for hereditary spastic paraplegia uncover a role of PI4K2A in autophagic lysosome reformation","volume":"17","author":"Khundadze","year":"2021","journal-title":"Autophagy"},{"key":"ref_28","unstructured":"Malchiodi, Z.X. (2024). Natural Killer Cells in the Pancreatic Ductal Adenocarcinoma Tumor Microenvironment. [Ph.D. Thesis, Georgetown University]."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Oliveira, A.C.S., Rezende, L., Gorshkov, V., Melo-Braga, M.N., Verano-Braga, T., Fernandes-Braga, W., Guadalupe, J.L.d.M., de Menezes, G.B., Kjeldsen, F., and de Andrade, H.M. (2022). Biological and molecular effects of Trypanosoma cruzi residence in a LAMP-deficient intracellular environment. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.788482"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6268","DOI":"10.1038\/s41467-020-20019-0","article-title":"Immune suppressive landscape in the human esophageal squamous cell carcinoma microenvironment","volume":"11","author":"Zheng","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e1490853","DOI":"10.1080\/2162402X.2018.1490853","article-title":"TGF-\u03b21 programmed myeloid-derived suppressor cells (MDSC) acquire immune-stimulating and tumor killing activity capable of rejecting established tumors in combination with radiotherapy","volume":"7","author":"Jayaraman","year":"2018","journal-title":"Oncoimmunology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"14049","DOI":"10.1038\/ncomms14049","article-title":"Massively parallel digital transcriptional profiling of single cells","volume":"8","author":"Zheng","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wolf, F.A., Angerer, P., and Theis, F.J. (2018). SCANPY: Large-scale single-cell gene expression data analysis. Genome Biol., 19.","DOI":"10.1186\/s13059-017-1382-0"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Bartha, \u00c1., and Gy\u0151rffy, B. (2021). TNMplot.com: A Web Tool for the Comparison of Gene Expression in Normal, Tumor and Metastatic Tissues. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052622"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"W556","DOI":"10.1093\/nar\/gkz430","article-title":"GEPIA2: An enhanced web server for large-scale expression profiling and interactive analysis","volume":"47","author":"Tang","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"W509","DOI":"10.1093\/nar\/gkaa407","article-title":"TIMER2.0 for analysis of tumor-infiltrating immune cells","volume":"48","author":"Li","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3892\/ijo.2016.3522","article-title":"Direct regulation of LAMP1 by tumor-suppressive microRNA-320a in prostate cancer","volume":"49","author":"Okato","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1369\/jhc.2010.957191","article-title":"Antigen retrieval immunohistochemistry: Review and future prospects in research and diagnosis over two decades","volume":"59","author":"Shi","year":"2011","journal-title":"J. Histochem. Cytochem."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Bankhead, P., Loughrey, M.B., Fern\u00e1ndez, J.A., Dombrowski, Y., McArt, D.G., Dunne, P.D., McQuaid, S., Gray, R.T., Murray, L.J., and Coleman, H.G. (2017). QuPath: Open source software for digital pathology image analysis. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-17204-5"},{"key":"ref_41","first-page":"52521","article-title":"The bioconjugation and radiosynthesis of 89Zr-DFO-labeled antibodies","volume":"96","author":"Zeglis","year":"2015","journal-title":"J. Vis. Exp. JoVE"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/nprot.2010.13","article-title":"Conjugation and radiolabeling of monoclonal antibodies with zirconium-89 for PET imaging using the bifunctional chelate p-isothiocyanatobenzyl-desferrioxamine","volume":"5","author":"Vosjan","year":"2010","journal-title":"Nat. Protoc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"893","DOI":"10.7150\/thno.9425","article-title":"An EGFR targeted PET imaging probe for the detection of colonic adenocarcinomas in the setting of colitis","volume":"4","author":"Turker","year":"2014","journal-title":"Theranostics"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/8\/1122\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:17:03Z","timestamp":1760033823000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/8\/1122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,27]]},"references-count":43,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ph18081122"],"URL":"https:\/\/doi.org\/10.3390\/ph18081122","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,27]]}}}