Department of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA.
Bioorg Med Chem Lett. 2013 Sep 15;23(18):5049-52. doi: 10.1016/j.bmcl.2013.07.046. Epub 2013 Jul 29.
Aminopeptidase N (APN) is known to play important roles in tumor angiogenesis, tumor cell invasion, and metastasis. Thus, APN is an attractive biomarker for imaging tumor angiogenesis. Here we report results obtained from biodistribution and single photon emission computed tomography (SPECT) imaging studies of a technetium-99m labeled probestin (a potent APN inhibitor) conjugate containing a tripeptide, Asp-DAP-Cys (DAP=2,3-diaminopropionic acid), chelator and a 8-amino-3,6-dioxaoctanoic acid (PEG2) linker conducted in nude mice xenografted with HT-1080 human fibrosarcoma tumors (APN-positive tumors). These results collectively demonstrate that (99m)Tc-probestin uptake by tumors and other APN expressing tissues in vivo is specific and validate the use of probestin as a vector for targeting APN in vivo.
天冬氨酰肽酶 N（APN）已知在肿瘤血管生成、肿瘤细胞侵袭和转移中发挥重要作用。因此，APN 是一种有吸引力的肿瘤血管生成成像生物标志物。在这里，我们报告了在裸鼠中进行的锝-99m 标记的 probestin（一种有效的 APN 抑制剂）缀合物的生物分布和单光子发射计算机断层扫描（SPECT）成像研究结果，该缀合物包含三肽 Asp-DAP-Cys（DAP=2,3-二氨基丙酸）、螯合剂和 8-氨基-3,6-二氧代辛酸（PEG2）接头，这些研究在 HT-1080 人纤维肉瘤肿瘤（APN 阳性肿瘤）的异种移植裸鼠中进行。这些结果共同表明，（99m）Tc-probestin 在体内肿瘤和其他表达 APN 的组织中的摄取是特异性的，并验证了 probestin 作为体内靶向 APN 的载体的用途。
