Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Mol Imaging. 2022 Jul 4;2022:7456365. doi: 10.1155/2022/7456365. eCollection 2022.
Extracellular acidity is a marker of highly aggressive breast cancer (BC). pH-low insertion peptides (pHLIPs) target the acidic tumor microenvironment. This study evaluates the distribution and therapeutic efficacy of radioiodine-labeled pHLIP variant 3 (Var3) in a mouse model of BC.
The binding of fluorescein isothiocyanate (FITC)- or radioiodine-125 (I) labeled Var3-pHLIP to MDA-MB-231, 4T1, and SK-BR-3 BC cell lines under different pH values was evaluated in vitro. The distribution of I-labeled Var3-pHLIP and wild-type- (WT-) pHLIP in tumor-bearing mice was analyzed in vivo using micro-SPECT/CT imaging. The therapeutic efficacy of radioiodine-131 (I)-labeled Var3-pHLIP in MDA-MB-231 xenografts was evaluated by relative tumor volume measurement and immunohistochemical analysis.
The binding ability of FITC- or I-labeled Var3-pHLIP to tumor cells increased with the decrease in pH. The tumor-to-background ratio of I-Var3-pHLIP in BC xenografts showed the best imaging contrast at 24 h or 48 h postinjection. The uptake of I-Var3-pHLIP in MDA-MB-231 xenografts at 2 h postinjection was significantly higher than that of I-WT-pHLIP (3.76 ± 0.37 vs. 2.87 ± 0.60%ID/g, = 0.046). The relative tumor volume in MDA-MB-231 xenografts was significantly lower in the I-Var3-pHLIP-treated group than in the groups treated with Var3-pHLIP ( = 0.027), I ( = 0.001), and saline ( < 0.001). The I-Var 3-pHLIP group presented a lower expression of Ki67 and a higher expression of caspase 3.
Radioiodine-labeled Var3-pHLIP effectively targeted BC cells in an acidic environment and inhibited the growth of MDA-MB-231 xenografts by ionizing radiation.
细胞外酸度是高度侵袭性乳腺癌（BC）的标志物。pH 低插入肽（pHLIPs）靶向酸性肿瘤微环境。本研究评估放射性碘标记 pHLIP 变体 3（Var3）在 BC 小鼠模型中的分布和治疗效果。
在不同 pH 值下，评估荧光素异硫氰酸酯（FITC）或放射性碘 125（I）标记的 Var3-pHLIP 与 MDA-MB-231、4T1 和 SK-BR-3 BC 细胞系的结合情况。使用 micro-SPECT/CT 成像技术在荷瘤小鼠体内分析 I 标记的 Var3-pHLIP 和野生型（WT）-pHLIP 的分布。通过相对肿瘤体积测量和免疫组织化学分析评估放射性碘 131（I）标记的 Var3-pHLIP 在 MDA-MB-231 异种移植瘤中的治疗效果。
FITC 或 I 标记的 Var3-pHLIP 与肿瘤细胞的结合能力随 pH 值的降低而增加。BC 异种移植瘤中 I-Var3-pHLIP 的肿瘤与背景比在注射后 24 或 48 小时显示出最佳的成像对比。注射后 2 小时，I-Var3-pHLIP 在 MDA-MB-231 异种移植瘤中的摄取量明显高于 I-WT-pHLIP（3.76±0.37% vs. 2.87±0.60%ID/g， = 0.046）。I-Var3-pHLIP 治疗组的 MDA-MB-231 异种移植瘤的相对肿瘤体积明显低于 Var3-pHLIP 治疗组（ = 0.027）、I 治疗组（ = 0.001）和生理盐水治疗组（ < 0.001）。I-Var3-pHLIP 组 Ki67 表达降低，caspase 3 表达升高。
放射性碘标记的 Var3-pHLIP 可有效靶向酸性环境中的 BC 细胞，并通过电离辐射抑制 MDA-MB-231 异种移植瘤的生长。
