Characterization of chemical, radiochemical and optical properties of a dual-labeled MMP-9 targeting peptide.
Characterization of chemical, radiochemical and optical properties of a dual-labeled MMP-9 targeting peptide.
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DOI：
10.1016/j.bmc.2011.04.054
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发表时间：
2011-06-15
影响因子：
3.5
通讯作者：
Sevick-Muraca, Eva M.
中科院分区：
文献类型：
--
作者：
Azhdarinia, Ali;Wilganowski, Nathaniel;Robinson, Holly;Ghosh, Pradip;Kwon, Sunkuk;Lazard, ZaWaunyka W.;Davis, Alan R.;Olmsted-Davis, Elizabeth;Sevick-Muraca, Eva M.
光学成像具有与核成像类似的敏感性，并导致了具有双标记核/近红外(NIR)试剂的多模式方法的出现。68Ga(t1/2=68min)标记多肽在临床前和临床研究中的影响越来越大，这为将近红外成像的高空间分辨率与临床接受的正电子发射断层扫描(PET)相结合提供了一个很有希望的机会。以前，双标记试剂是用寿命更长的放射性金属制备的，并且没有显示出由于放射性标记而对光学性质的有害影响。在这项研究中，我们选择了一个靶向基质金属蛋白酶-2/9的多肽(M2)，并用IRDye 800CW和68Ga进行了双重标记。由于68Ga络合通常需要较低的pH(3.5-4)和较高的加热温度(95℃)，我们试图评估68Ga标记对M2光学性质的影响。提出了一种制备68Ga-M2的有效方法，并对反应条件进行了优化。在PBS、DTPA和血清中进行了稳定性研究，在每种条件下都明显地获得了高水平的完整试剂。将多个报告添加到靶向剂中增加了表征和验证的复杂性，因此不仅需要测试以确保试剂在化学和放射化学上稳定，而且在光学上也是如此。因此，使用荧光分光光度计以及通过高效液相色谱的荧光检测来评估荧光性质。结果表明，68Ga标记条件不影响试剂的荧光性质。该试剂随后被用于异位骨化(HO)小鼠模型的体内成像，其中激活的MMP-9表达是矿化之前的早期生物标记物。虽然68Ga-络合大大降低了多肽的结合亲和力，并否定了示踪剂在PET上的摄取，但近红外成像显示了与基质金属蛋白酶-9表达相关的一致的荧光信号。这证明了68Ga/NIR用于其他多肽或小分子的双重标记用于多模式分子成像的可行性。
Optical imaging possesses similar sensitivity to nuclear imaging and has led to the emergence of multimodal approaches with dual-labeled nuclear/near-infrared (NIR) agents. The growing impact of 68Ga (t1/2 = 68 min) labeled peptides on preclinical and clinical research offers a promising opportunity to merge the high spatial resolution of NIR imaging with the clinically-accepted positron emission tomography (PET). Previously, dual-labeled agents have been prepared with longer-lived radiometals and showed no detrimental effects on optical properties as a result of radiolabeling. In this study, we selected a peptide (M2) that targets MMP-2/9 and is dual-labeled with IRDye 800CW and 68Ga. Since 68Ga chelation typically requires low pH (3.5–4) and elevated heating temperatures (95°C), we sought to evaluate the impact of 68Ga labeling on the optical properties of M2. An efficient method for preparation of 68Ga-M2 was developed and reaction conditions were optimized. Stability studies in PBS, DTPA, and serum were performed and high levels of intact agent were evident under each condition. The addition of multiple reporters to a targeting agent adds further complexity to the characterization and validation and thus requires not only testing to ensure the agent is stable chemically and radiochemically, but also optically. Therefore, fluorescence properties were evaluated using a spectrofluorometer as well as by fluorescence detection via HPLC. It was determined that 68Ga-labeling conditions did not impair the fluorescent properties of the agent. The agent was then used for in vivo imaging in a mouse model of heterotopic ossification (HO) with activated MMP-9 expression as an early biomarker which precedes mineralization. Although 68Ga-complexation greatly reduced binding affinity of the peptide and negated tracer uptake on PET, NIR imaging showed consistent fluorescent signal that correlated to MMP-9 expression. This attests to the feasibility of using 68Ga/NIR for dual-labeling of other peptides or small molecules for multimodality molecular imaging.
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影响因子：
3.1
作者：
Hanaoka, Hirofurni;Mukai, Takahiro;Saji, Hideo
通讯作者：
Saji, Hideo
DOI：
10.1016/j.bbrc.2009.10.017
发表时间：
2009-12-18
影响因子：
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作者：
Chen, Ying;Dhara, Surajit;Banerjee, Sangeeta Ray;Byun, Youngjoo;Pullambhatla, Mrudula;Mease, Ronnie C.;Pomper, Martin G.
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Pomper, Martin G.
DOI：
10.1007/s00259-004-1486-0
发表时间：
2004-08-01
影响因子：
9.1
作者：
Meyer, GJ;Mäcke, H;Hofmann, M
通讯作者：
Hofmann, M
影响因子：
46.9
作者：
Becker, A;Hessenius, C;Grötzinger, C
通讯作者：
Grötzinger, C
DOI：
10.1007/s00259-004-1702-y
发表时间：
2005-04-01
影响因子：
9.1
作者：
Breeman, WAP;de Jong, M;Krenning, EP
通讯作者：
Krenning, EP