CD133 as a biomarker for an autoantibody-to-immunoPET paradigm for the early detection of small cell lung cancer Journal Article
| Authors: | Kunihiro, A. G.; Sarrett, S. M.; Lastwika, K. J.; Solan, J. L.; Pisarenko, T.; Keinänen, O.; Rodriguez, C.; Taverne, L. R.; Fitzpatrick, A. L.; Li, C. I.; McGarry Houghton, A.; Zeglis, B. M.; Lampe, P. D. |
| Article Title: | CD133 as a biomarker for an autoantibody-to-immunoPET paradigm for the early detection of small cell lung cancer |
| Abstract: | Small cell lung cancer (SCLC) is a deadly neuroendocrine tumor for which there are no screening methods sensitive enough to facilitate early, effective intervention. We propose targeting the neuroendocrine tumor neoantigen CD133 via antibody-based early detection and PET (immunoPET) to facilitate earlier and more accurate detection of SCLC. Methods: RNA sequencing datasets, immunohistochemistry, flow cytometry, and Western blots were used to quantify CD133 expression in healthy and SCLC patients. CD133 was imaged in vivo using near-infrared fluorescence (NIRF) immunoimaging, and 89Zr immunoPET. Anti(a)-CD133 autoantibody levels were measured in SCLC patient plasma using antibody microarrays. Results: Across 6 publicly available datasets, CD133 messenger RNA was found to be higher in SCLC tumors than in other tissues, including healthy or normal adjacent lung and non-SCLC samples. Critically, the upregulation of CD133 messenger RNA in SCLC was associated with a significant increase (hazard ratio, 2.62) in death. CD133 protein was expressed in primary human SCLC, in SCLC patient-derived xenografts, and in both SCLC cell lines tested (H82 and H69). Using an H82 xenograft mouse model, we first imaged CD133 expression with NIRF. Both in vivo and ex vivo NIRF clearly showed that a fluorophore-tagged aCD133 homed to lung tumors. Next, we validated the noninvasive visualization of subcutaneous and orthotopic H82 xenografts via immunoPET. An aCD133 antibody labeled with the positron-emitting radiometal 89Zr demonstrated significant accumulation in tumor tissue while producing minimal uptake in healthy organs. Finally, plasma aCD133 autoantibodies were found in subjects from cohort studies up to 1 year before SCLC diagnosis. Conclusion: In light of these findings, we conclude that the presence of aCD133 autoantibodies in a blood sample followed by CD133-targeted 89Zr-immunoPET could be an effective early detection screening strategy for SCLC. |
| Keywords: | receptor; autoantibody; therapy; expression; target; sclc; immunopet; humanized monoclonal-antibody; emission-tomography; cd133; glioblastoma stem-cells |
| Journal Title: | Journal of Nuclear Medicine |
| Volume: | 63 |
| Issue: | 11 |
| ISSN: | 0161-5505 |
| Publisher: | Society of Nuclear Medicine |
| Date Published: | 2022-11-01 |
| Start Page: | 1701 |
| End Page: | 1707 |
| Language: | English |
| ACCESSION: | WOS:000968142600015 |
| DOI: | 10.2967/jnumed.121.263511 |
| PROVIDER: | wos |
| PMCID: | PMC9635686 |
| PUBMED: | 35483965 |
| Notes: | Article -- Source: Wos |
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