Progesterone-targeted magnetic resonance imaging probes.
Progesterone-targeted magnetic resonance imaging probes.
复制标题
DOI：
10.1021/bc500265h
复制
发表时间：
2014-08-20
影响因子：
4.7
通讯作者：
Meade, Thomas J.
中科院分区：
文献类型：
--
作者：
Townsend, Taryn R.;Moyle-Heyrman, Georgette;Sukerkar, Preeti A.;MacRenaris, Keith W.;Burdette, Joanna E.;Meade, Thomas J.
在激素依赖性疾病中，测定孕激素受体（PR）状态对确定疾病预后和监测治疗反应至关重要。开发一种无创监测这些过程的方法将对早期发现、成本、重复测量和个性化治疗方案产生重大影响。磁共振成像（MRI）被广泛认为是一种可以进行纵向研究的技术，PR靶向MR探针可以通过提供对比增强来解决临床问题，无需活检即可报告PR状态。市售磁共振造影剂通常通过静脉注射给药，而类固醇是皮下给药。递送途径对于类固醇修饰的MRI造影剂向富含pr的组织积累是否重要尚不清楚。为了解决这个问题，修改孕酮与钆螯合物的化学连接，使MR探针具有更高的水溶性和更低的细胞毒性，并能够通过血液给药。这种特性的代价是对PR的亲和力较低，穿过细胞膜的能力下降，最终并不能改善PR靶向MR探针在体内向富含PR的组织或肿瘤的递送。总的来说，这些研究很重要，因为它们证明了靶向造影剂需要优化类固醇和钆螯合物的递送和受体结合，才能在体内实现最佳翻译。
Determination of progesterone receptor (PR) status in hormone-dependent diseases is essential in ascertaining disease prognosis and monitoring treatment response. The development of a noninvasive means of monitoring these processes would have significant impact on early detection, cost, repeated measurements, and personalized treatment options. Magnetic resonance imaging (MRI) is widely recognized as a technique that can produce longitudinal studies, and PR-targeted MR probes may address a clinical problem by providing contrast enhancement that reports on PR status without biopsy. Commercially available MR contrast agents are typically delivered via intravenous injection, whereas steroids are administered subcutaneously. Whether the route of delivery is important for tissue accumulation of steroid-modified MRI contrast agents to PR-rich tissues is not known. To address this question, modification of the chemistry linking progesterone with the gadolinium chelate led to MR probes with increased water solubility and lower cellular toxicity and enabled administration through the blood. This attribute came at a cost through lower affinity for PR and decreased ability to cross the cell membrane, and ultimately it did not improve delivery of the PR-targeted MR probe to PR-rich tissues or tumors in vivo. Overall, these studies are important, as they demonstrate that targeted contrast agents require optimization of delivery and receptor binding of the steroid and the gadolinium chelate for optimal translation in vivo.
登录
查看更多内容
影响因子：
7.6
作者：
Meng Q;Li Z
通讯作者：
Li Z
影响因子：
2.4
作者：
Boruban, Melih C.;Altundag, Kadri;Blankstein, Josef
通讯作者：
Blankstein, Josef
DOI：
10.2214/ajr.10.4665
发表时间：
2011-12
期刊：
AJR. American journal of roentgenology
影响因子：
--
作者：
El Khouli RH;Macura KJ;Kamel IR;Jacobs MA;Bluemke DA
通讯作者：
Bluemke DA
影响因子：
120.1
作者：
Leeson, Paul D.;Springthorpe, Brian
通讯作者：
Springthorpe, Brian
DOI：
10.2967/jnumed.112.103465
发表时间：
2012-07
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Fowler AM;Chan SR;Sharp TL;Fettig NM;Zhou D;Dence CS;Carlson KE;Jeyakumar M;Katzenellenbogen JA;Schreiber RD;Welch MJ
通讯作者：
Welch MJ