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, ⁶⁸GaGa/¹⁷⁷LuLu-DOTA-COL, designed to integrate noninvasive PET imaging with local radiotherapy by selectively targeting exposed type I collagen post-PEI. ⁶⁸GaGa-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 ⁶⁸GaGa-DOTA-COL and ¹⁸FFDG, along with histology and immunohistochemistry, comprehensively assessed collagen remodeling, recurrence, and therapeutic response. PET/CT revealed pronounced ⁶⁸GaGa-DOTA-COL accumulation during five days post-PEI, suggesting that PEI-induced exposure of type I collagen enabled a therapeutic window. Therapeutic ¹⁷⁷LuLu-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 ¹⁷⁷LuLu-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.
Wang et al. (Tue,) studied this question.