You are here
CD133 as a Biomarker for an Autoantibody-to-ImmunoPET Paradigm for the Early Detection of Small Cell Lung Cancer.
Tuesday,2023-01-31 13:13 America/Los_Angeles — ecterry
| Title | CD133 as a Biomarker for an Autoantibody-to-ImmunoPET Paradigm for the Early Detection of Small Cell Lung Cancer. |
| Publication Type | Journal Article |
| Year of Publication | 2022 |
| Authors | Kunihiro, AG, Sarrett, SM, Lastwika, KJ, Solan, JL, Pisarenko, T, Keinänen, O, Rodriguez, C, Taverne, LR, Fitzpatrick, AL, Li, CI, A Houghton, MG, Zeglis, BM, Lampe, PD |
| Journal | J Nucl Med |
| Volume | 63 |
| Issue | 11 |
| Pagination | 1701-1707 |
| Date Published | 2022 Nov |
| ISSN | 1535-5667 |
| Keywords | Animals, Autoantibodies, Biomarkers, Cell Line, Tumor, Disease Models, Animal, Early Detection of Cancer, Humans, Lung Neoplasms, Mice, Mice, Nude, Neuroendocrine Tumors, Positron-Emission Tomography, RNA, Messenger, Small Cell Lung Carcinoma |
| Abstract | <p>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. RNA sequencing datasets, immunohistochemistry, flow cytometry, and Western blots were used to quantify CD133 expression in healthy and SCLC patients. CD133 was imaged using near-infrared fluorescence (NIRF) immunoimaging, and Zr immunoPET. Anti(α)-CD133 autoantibody levels were measured in SCLC patient plasma using antibody microarrays. 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 and NIRF clearly showed that a fluorophore-tagged αCD133 homed to lung tumors. Next, we validated the noninvasive visualization of subcutaneous and orthotopic H82 xenografts via immunoPET. An αCD133 antibody labeled with the positron-emitting radiometal Zr demonstrated significant accumulation in tumor tissue while producing minimal uptake in healthy organs. Finally, plasma αCD133 autoantibodies were found in subjects from cohort studies up to 1 year before SCLC diagnosis. In light of these findings, we conclude that the presence of αCD133 autoantibodies in a blood sample followed by CD133-targeted Zr-immunoPET could be an effective early detection screening strategy for SCLC.</p> |
| DOI | 10.2967/jnumed.121.263511 |
| Alternate Journal | J Nucl Med |
| PubMed ID | 35483965 |
| PubMed Central ID | PMC9635686 |
| Grant List | R01 CA204167 / CA / NCI NIH HHS / United States U01 CA221046 / CA / NCI NIH HHS / United States R01 CA240963 / CA / NCI NIH HHS / United States U01 CA185097 / CA / NCI NIH HHS / United States U01 CA186157 / CA / NCI NIH HHS / United States U01 CA152637 / CA / NCI NIH HHS / United States R01 CA244327 / CA / NCI NIH HHS / United States R21 EB030275 / EB / NIBIB NIH HHS / United States R01 CA243328 / CA / NCI NIH HHS / United States P50 CA228944 / CA / NCI NIH HHS / United States F32 CA261055 / CA / NCI NIH HHS / United States T32 CA009657 / CA / NCI NIH HHS / United States KL2 TR002317 / TR / NCATS NIH HHS / United States R25 GM086304 / GM / NIGMS NIH HHS / United States P30 CA015704 / CA / NCI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States HHSN268201800001C / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States 75N92021D00006 / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States |
ePub date:
22/11