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200，000例新发病例和40，000例死亡。迫切需要用于检测原发性和转移性乳腺癌的新方法来增加患者的存活率。目前的成像技术在恶性肿瘤的诊断和分期的准确性方面是有限的。目前CT、PET、MRI和超声诊断的准确性可能低至50%，并且很大一部分患者被误诊或分期不足。MRI具有高空间分辨率和大穿透深度，可提供形态和解剖信息，因此是一种有前途的成像方式，用于乳腺癌术前分期和监测肿瘤对治疗的反应。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。基于MRI的无电离辐射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，需要改进MR成像的特异性和灵敏度，以提高清晰度和诊断准确性。在这个项目中，我们提出了一个癌症生物标志物靶向金属富勒烯造影剂具有非常高的分子弛豫的发展。在许多临床前研究中，金属富勒烯已被证明是比基于钆的螯合物更好的T1加权成像剂。所提出的癌症成像剂将Luna的有前途的Hydrochalarone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程度的准确性和分期，并消除假阳性和假阴性。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优势。

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.