NOVEL RADIOLABELED PEPTIDES FOR NON-INVASIVE BREAST CANCER IMAGING

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 乳腺癌是最常见的癌症，也是女性癌症死亡的第二大原因。不幸的是，转移性乳腺癌尚无根治方法。乳腺癌的早期诊断为患者提供了治愈或延长生存的最佳机会。目前的[18F]FDG(2-[18F]氟-2-脱氧-D-葡萄糖)PET(正电子发射断层扫描)成像因其相对较低的灵敏度和特异性而限制了其应用。迫切需要新的、更有效的成像探针来提高对原发、转移和复发乳腺癌的检测准确率。 我们的策略是提高乳腺癌检测的准确性，重点是开发针对GnRH受体的新型放射性标记促性腺激素释放激素(GnRH)多肽。由于GnRH受体在人乳腺癌细胞和标本上的过度表达，因此它是该项目中开发更有效的乳腺癌特异性成像探针的独特分子靶点。在这个项目中，我们将在人乳腺癌细胞和异种移植瘤中合成和评估一系列新型的放射性标记GnRH多肽。我们的中心假设和研究设计得到了我们积极的初步结果的有力支持。该项目的积极结果将首次证明使用放射性标记的GnRH多肽进行乳腺癌成像的可行性，并为设计新的、更有效的乳腺癌诊断和治疗药物提供新的见解。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death in women. Unfortunately, no curative treatment exists for metastatic breast cancer. Early diagnosis of breast cancer provides the patients the best opportunities for cures or prolonged survival. Current [18F]FDG (2-[18F]fluoro-2-deoxy-D-glucose) PET (positron emission tomography) imaging has limited use by relatively low sensitivity and specificity. Novel and more effective imaging probes are urgently needed to improve the detection accuracy of primary, metastatic and recurrent breast cancers. Our strategy to improve the detection accuracy for breast cancer focuses on developing novel radiolabeled gonadotropin-releasing hormone (GnRH) peptides to target the GnRH receptors. GnRH receptor is a distinct molecular target in this project for developing more effective breast cancer-specific imaging probes due to its over-expression on human breast cancer cells and specimens. We will synthesize and evaluate a series of novel radiolabeled GnRH peptides in human breast cancer cells and xenografts in this project. Our central hypothesis and research design are strongly supported by our positive preliminary results. Positive results from this project will firstly demonstrate the feasibility of using the radiolabeled GnRH peptides for breast cancer imaging and provide new insight into the design of novel and more effective diagnostic and therapeutic agents for breast cancer.