Improved Metallofullerene MRI Contrast Agent for Cancer Diagnosis

描述（由申请人提供）：乳腺癌是女性中最常见的癌症，在美国每年约有20万新病例和4万死亡病例。为了提高患者的生存率，迫切需要新的方法来检测原发性和转移性乳腺癌。目前的影像技术在诊断的准确性和恶性肿瘤的分期是有限的。目前CT、PET、MRI和超声诊断的准确率可低至50%，相当一部分患者要么被误诊，要么分期不足。MRI可提供空间分辨率高、穿透深度大的形态学和解剖学信息，是乳腺癌术前分期和监测肿瘤治疗反应的一种很有前景的成像方式。MRI是非侵入性的，优于使用x射线辐射的CT和使用放射性标记剂的核成像。在不暴露于电离辐射的情况下，以核磁共振成像为基础的癌症诊断将对临床癌症护理和公共卫生产生极大的兴趣。然而，需要提高MR成像的特异性和敏感性来提高清晰度和诊断准确性。在本项目中，我们建议开发一种具有极高分子弛豫度的靶向癌症生物标志物的金属富勒烯造影剂。在许多临床前研究中，金属富勒烯已被证明是一种比钆基螯合剂更好的t1加权显像剂。该提议的癌症显像剂将Luna的前景看好的氢查拉酮造影剂和血管生成靶向分子结合在一个聚合物纳米颗粒中。我们的目标是开发一种改进的造影剂，用于恶性疾病患者的MRI。它可用于提高癌症恶性的准确性和分期，并消除假阳性和假阴性。这项拟议的临床前研究旨在证明这种纳米技术支持的癌症诊断的技术和商业价值。

DESCRIPTION (provided by applicant): Breast cancer is the most common cancer in women with about 200,000 new cases and 40,000 deaths each year in the United States. Novel approaches for the detection of primary and metastatic breast cancers are urgently needed to increase the survival of patients. Current imaging techniques are limited in accuracy of diagnosis and staging of malignancy. Accuracy in current CT, PET, MRI and ultrasound diagnosis can be as low as 50% and a significant portion of patients are either misdiagnosed or under staged. MRI can provide both morphological and anatomical information with high spatial resolution and large penetration depth, thus a promising imaging modality for preoperative staging of breast cancer and monitoring tumor response to treatment. MRI is non-invasive and better than CT that uses x-ray radiation and nuclear imaging that uses radiolabeled agents. MRI-based cancer diagnosis without exposure to ionizing radiation will be of great interest to clinical cancer care and public health. However improvements in MR imaging specificity and sensitivity are needed to improve clarity and diagnostic accuracy. In this project we propose the development of a cancer biomarker-targeting metallofullerene contrast agent with very high molecular relaxivity. Metallofullerene has been demonstrated to be a better T1-weighted imaging agent than gadolinium- based chelates in a number of preclinical studies. The proposed cancer imaging agent incorporates Luna's promising Hydrochalarone contrast agent and angiogenic targeting molecules in one polymeric nanoparticle. Our goal is to develop an improved contrast agent for use with MRI in patients with malignant disease. It may be used to improve accuracy and staging of cancer malignancy, and to eliminate false positives and false negatives. The proposed preclinical study is designed to demonstrate the technical and commercial merits of this nanotechnology-enabled cancer diagnosis.