ArticleJournal of nanobiotechnology2026
Ablation-induced collagen exposure enables dual-modal nuclear imaging-guided local radionuclide therapy.
Article in Journal of nanobiotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Percutaneous ethanol injection (PEI) is a first-line ablation therapy for hepatocellular carcinoma (HCC), while effective postoperative management remains challenging. Type I collagen in HCC stroma, linked to resistance and recurrence, is a promising target for imaging-guided theranostic. We developed a dual-modality tracer, [⁶⁸Ga]Ga/[¹⁷⁷Lu]Lu-DOTA-COL, designed to integrate noninvasive PET imaging with local radiotherapy by selectively targeting exposed type I collagen post-PEI. [⁶⁸Ga]Ga-DOTA-COL exhibited high radiochemical purity (> 99%), strong collagen affinity (IC₅₀ = 8.44 nM), and favorable in vivo PET imaging specificity. In a murine HCC model undergoing PEI, longitudinal PET/CT with [⁶⁸Ga]Ga-DOTA-COL and [¹⁸F]FDG, along with histology and immunohistochemistry, comprehensively assessed collagen remodeling, recurrence, and therapeutic response. PET/CT revealed pronounced [⁶⁸Ga]Ga-DOTA-COL accumulation during five days post-PEI, suggesting that PEI-induced exposure of type I collagen enabled a therapeutic window. Therapeutic [¹⁷⁷Lu]Lu-DOTA-COL administered within this period effectively suppressed tumor regrowth, as confirmed by SPECT and biodistribution, with selective uptake in collagen-exposed regions. PEI induced CD163⁺ M2-like macrophages infiltration, promoting an immunosuppressive microenvironment and recurrence, whereas [¹⁷⁷Lu]Lu-DOTA-COL reduced M2 macrophages, increased CD8⁺ and CD4⁺ T cell infiltration, and markedly suppressed Ki67 expression. These findings provide a rationale paradigm for improving postoperative management following PEI and other local ablation therapies.
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