水溶性孕激素缀合物探针用于激素相关癌症磁共振成像的合成与生物学评价。
Synthesis and biological evaluation of water-soluble progesterone-conjugated probes for magnetic resonance imaging of hormone related cancers.
机构信息
Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, USA.
出版信息
Bioconjug Chem. 2011 Nov 16;22(11):2304-16. doi: 10.1021/bc2003555. Epub 2011 Oct 5.
Abstract
Progesterone receptor (PR) is strongly associated with disease prognosis and therapeutic efficacy in hormone-related diseases such as endometriosis and breast, ovarian, and uterine cancers. Receptor status is currently determined by immunohistochemistry assays. However, noninvasive PR imaging agents could improve disease detection and help elucidate pathological molecular pathways, leading to new therapies and animal disease models. A series of water-soluble PR-targeted magnetic resonance imaging (MRI) probes were synthesized using Cu(I)-catalyzed click chemistry and evaluated in vitro and in vivo. These agents demonstrated activation of PR in vitro and preferential accumulation in PR(+) compared to PR(-) human breast cancer cells with low toxicity. In xenograft tumor models, the agents demonstrated enhanced signal intensity in PR(+) tumors compared to PR(-) tumors. The results suggest that these agents may be promising MRI probes for PR(+) diseases.
摘要
孕激素受体（PR）与子宫内膜异位症和乳腺癌、卵巢癌和子宫癌等激素相关疾病的预后和治疗效果密切相关。受体状态目前通过免疫组织化学检测来确定。然而，非侵入性的 PR 成像剂可以提高疾病检测的准确性，并有助于阐明病理分子途径，从而为新的治疗方法和动物疾病模型提供依据。本研究使用铜（I）催化的点击化学合成了一系列水溶性 PR 靶向磁共振成像（MRI）探针，并对其进行了体外和体内评估。这些探针在体外表现出 PR 的激活作用，并在体外表现出对 PR（+）人乳腺癌细胞的优先积累，且毒性较低。在异种移植肿瘤模型中，与 PR（-）肿瘤相比，这些探针在 PR（+）肿瘤中表现出增强的信号强度。这些结果表明，这些探针可能是 PR（+）疾病有前途的 MRI 探针。
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