ImmunoPET for mesothelin positive tissues using bio-orthogonal in-vivo click chemistry Journal Article
| Authors: | Pratt, E. C.; Mandleywala, K.; Bauer, D.; Bolaender, A.; Chao, G.; Castanares, M. A.; Collins, E. C.; Lewis, J. S. |
| Article Title: | ImmunoPET for mesothelin positive tissues using bio-orthogonal in-vivo click chemistry |
| Abstract: | Mesothelin is a membrane bound antigen overexpressed in a wide array of cancers including ovarian, pancreatic, lung, and triple negative breast cancers. Here a full-length IgG antibody developed against mesothelin, called MESO-HSS1 was conjugated for immunoPET imaging and assessed in-vivo in a H956 mesothelin positive model. Furthermore, random lysine conjugation as well as a site selective conjugation method were compared in two pretargeting models for overall tumor uptake alongside non target organs and tumor to organ ratios. Overall, [89Zr]Zr-DFO-MESO-HSS1 was found to be a suitable immunoPET radiotracer for the detection of the mesothelin low cancer line H596 as early as 24 h post injection with up to 20.1 % injected dose per gram by 144 h. Furthermore, in pretargeted models, lysine conjugation of TCO-Lys-MESO-HSS1 with [64Cu]Cu-Sar-Tz yielded the highest tumor uptake at 2.6 % injected dose per gram at 24 h. Imaging 4 h post injection of [18F]F-Al-NOTA-PEG7-Tz however was best with TCO-SS-MESO-HSS1 with improved tumor to organ ratios as expected from site selective modifications. High tumor to pancreas ratios suggests mesothelin imaging could be a highly effective diagnostic for pancreatic cancer identification. Together these data show MESO-HSS1 as a direct immunoPET or pretargeting agent as a viable immunoPET system for imaging mesothelin positive cancers. © 2025 Elsevier Inc. |
| Keywords: | controlled study; unclassified drug; human cell; nonhuman; positron emission tomography; neoplasm; mouse; animal tissue; animal experiment; animal model; in vivo study; in vitro study; drug distribution; western blotting; drug half life; surface plasmon resonance; immunoglobulin g antibody; drug binding; drug conjugation; mesothelin; click chemistry; immunopet; pretargeting; radiolabeling; human; article; nci-h596 cell line; immuno positron emission tomography; a-431 cell line; site-specific modification; meso hss1 antibody; caov-4 cell line |
| Journal Title: | Nuclear Medicine and Biology |
| Volume: | 148-149 |
| ISSN: | 0969-8051 |
| Publisher: | Elsevier Science Inc. |
| Date Published: | 2025-09-01 |
| Start Page: | 109051 |
| Language: | English |
| DOI: | 10.1016/j.nucmedbio.2025.109051 |
| PROVIDER: | scopus |
| PUBMED: | 40694891 |
| PMCID: | PMC12328198 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding MSK author is Jason S. Lewis -- Source: Scopus |
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