Molecular Imaging of the TGF-β Activating Integrin αvβ6 Detects Chronic Lung Allograft Dysfunction

Cano, M.; Bathula, C. S.; Liao, F.; Wieczorek Villas Boas, C.; Tao, Y.; Liu, Z.; Davis, V.; Ebenezer, R.; Cannady, A.; Zhou, D.; Liang, S.; Byers, D.; Krupnick, A.; Kreisel, D.; Dai, Z.; Rogers, B.; Gelman, A. E.

doi:10.64898/2026.01.07.698265

bioRxiv · 10.64898/2026.01.07.698265

Molecular Imaging of the TGF-β Activating Integrin αvβ6 Detects Chronic Lung Allograft Dysfunction

Cano, M.·Bathula, C. S.·Liao, F.·Wieczorek Villas Boas, C.·Tao, Y.·Liu, Z.·Davis, V.·Ebenezer, R.·Cannady, A.·Zhou, D.·Liang, S.·Byers, D.·Krupnick, A.·Kreisel, D.·Dai, Z.·Rogers, B.·Gelman, A. E.

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Abstract

TGF-{beta}-activating integrins promote solid-organ fibrosis, suggesting their use as a molecular marker of disease. Chronic lung allograft dysfunction (CLAD), a progressive fibrotic complication that limits lung transplant survival, is driven by intragraft TGF-{beta} activation. However, the expression patterns of TGF-{beta}-activating integrins remain undefined in lung transplants. Single-cell RNA sequencing in a mouse CLAD model revealed high levels of the TGF-{beta}-activating integrin v{beta}6, which was mainly localized to fibrosis-associated Krt8+ transitional alveolar cells (AT1/2), while tolerant transplants lacked both v{beta}6 expression and Krt8+AT1/2 cells. Molecular imaging with a newly developed positron emission tomography radiotracer specific for v{beta}6, [64Cu]Cu-DOTA-A20-K16R, showed significantly higher uptake in CLAD versus tolerant transplants. In contrast, [64Cu]Cu-DOTA-A20-K16R allograft uptake was reduced by treatments that lowered v{beta}6 expression and CLAD severity. Finally, [64Cu]Cu-DOTA-A20-K16R autoradiographic analysis on human explanted lungs with CLAD showed elevated activity that correlated with v{beta}6 expression. Collectively, these findings demonstrate the potential utility of v{beta}6 molecular imaging to detect CLAD pathogenesis.

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Cano, M., Bathula, C. S., Liao, F., Wieczorek Villas Boas, C., Tao, Y., Liu, Z., Davis, V., Ebenezer, R., Cannady, A., Zhou, D., Liang, S., Byers, D., Krupnick, A., Kreisel, D., Dai, Z., Rogers, B., Gelman, A. E.. 2026-01-08. Molecular Imaging of the TGF-β Activating Integrin αvβ6 Detects Chronic Lung Allograft Dysfunction. https://doi.org/10.64898/2026.01.07.698265

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