Agents for Specific NMR and SQUID Imaging of Prostate Cancer

用于前列腺癌特异性 NMR 和 SQUID 成像的试剂

• 批准号: 7315563
• 负责人: Laurel Owen Sillerud
• 金额: $ 49.31万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7315563
• 关键词: Address; American; Animals; Benign; Binding; Biological Models; Biology; Breast Cancer Cell; Cancer Cell Growth; Cancer Detection; Cancerous; Cell Adhesion; Cell Line; Cell surface; Cells; Cessation of life; Clinical Medicine; Clinical Trials; Complement; Detection; Development; Disease; Epitopes; Excision; Extracapsular; Flow Cytometry; Generations; Glutamate Carboxypeptidase II; Goals; Housing; Human; Image; In Vitro; Incidence; Integrins; Intravenous; Invasive; LNCaP; Laboratories; Ligands; Magnetic Resonance Imaging; Magnetism; Malignant Neoplasms; Malignant neoplasm of prostate; Measurement; Measures; Metastatic Lesion; Metastatic Prostate Cancer; Methods; Neurotensin; Neurotensin Receptors; New Mexico; Nuclear Magnetic Resonance; Nude Mice; Operative Surgical Procedures; Organ; PC3 cell line; Pathologist; Patients; Performance; Physics; Probability; Production; Program Development; Prostate; Prostate Adenocarcinoma; Prostatectomy; Prostatic Neoplasms; Puncture biopsy; Recruitment Activity; Relaxation; Research; Research Personnel; Resected; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; Series; Specimen; Staging; Techniques; Testing; Time; Tumor Volume; Urology; Work; Xenograft procedure; angiogenesis; anticancer research; base; cancer cell; density; experience; in vivo; innovation; iron oxide; lifetime risk; magnetic field; magnetic resonance spectroscopic imaging; male; mortality; nanoparticle; neoplastic cell; novel; particle; programs; prostate stem cell antigen; receptor; success; superconducting quantum interference device; tumor; tumor xenograft

DESCRIPTION (provided by applicant): We will develop critically-needed, non-invasive magnetic imaging agents for prostate cancer detection and staging, using a novel imaging approach that combines Magnetic Resonance Imaging (MRI) and Superconducting Quantum Interference Device (SQUID) imaging. Developing new methods for prostate cancer detection is important because it is one of the most common American-male cancers, and current detection methods result in inaccurate staging in as many as 40% of patients undergoing prostate resection. No imaging method currently exists which is specific for detecting and staging extracapsular or metastatic prostate cancer. We aim to address this problem by developing sensitive detection methods based on magnetic imaging agents that specifically target and bind to cancer cells. These agents will consist of specific cell surface recognition ligands attached to superparamagnetic iron oxide nanoparticles (SPIONs), which can be detected by both MRI and SQUID imaging. The cell surface markers these agents will target include Prostate Specific Membrane Antigen (PSMA), Prostate Stem Cell Antigen (PSCA), the Neurotensin Receptor (NTR), and an integrin intimately involved in angiogenesis (alpha-v-beta-3). To determine which agent performs the best for the specific detection of prostate cancer, we will develop in vitro and in vivo biological models, using human prostate cancer cell lines. Expression levels for these markers will be evaluated by RT-PCR and flow cytometry in a series of human prostate cancer cell lines (LNCaP, DU-145, PC-3, and C4-2, and lines developed in house from prostatectomy specimens). The binding of the imaging agents to these cells will be measured in vitro by MRI and SQUID to select the agents or combination of agents that will provide the best MRI contrast and the highest magnetic field for SQUID detection. The same cell lines will then be used to induce primary and metastatic prostate tumors in nude mice, and MRI and SQUID detection will be used to determine the sensitivity and specificity of these intravenous agents for locating and identifying disease in vivo. The proposed work will provide the thorough understanding needed for our next goal: clinical trials of these agents for the detection and staging of primary and metastatic prostate cancer in humans by MRI and SQUID imaging. Lay terms: We aim to develop a method to image prostate tumors and determine whether they are benign or cancerous using MRI. The proposed method would be more accurate and less invasive than needle biopsy.

描述（由申请人提供）：我们将使用结合磁共振成像（MRI）和超导量子干涉装置（SQUID）成像的新型成像方法，开发用于前列腺癌检测和分期的急需的非侵入性磁成像剂。开发新的前列腺癌检测方法非常重要，因为它是美国男性最常见的癌症之一，而目前的检测方法会导致多达 40% 的接受前列腺切除术的患者分期不准确。目前不存在专门用于检测和分期囊外或转移性前列腺癌的成像方法。我们的目标是通过开发基于磁成像剂的灵敏检测方法来解决这个问题，这些方法专门针对并结合癌细胞。这些试剂将由附着在超顺磁性氧化铁纳米颗粒 (SPION) 上的特定细胞表面识别配体组成，可以通过 MRI 和 SQUID 成像进行检测。这些药物将靶向的细胞表面标志物包括前列腺特异性膜抗原 (PSMA)、前列腺干细胞抗原 (PSCA)、神经降压素受体 (NTR) 和与血管生成密切相关的整合素 (α-v-β-3)。为了确定哪种试剂最适合前列腺癌的特异性检测，我们将使用人类前列腺癌细胞系开发体外和体内生物模型。这些标记物的表达水平将通过 RT-PCR 和流式细胞术在一系列人前列腺癌细胞系（LNCaP、DU-145、PC-3 和 C4-2，以及从前列腺切除标本中内部开发的细胞系）中进行评估。将通过 MRI 和 SQUID 在体外测量显像剂与这些细胞的结合，以选择将为 SQUID 检测提供最佳 MRI 对比度和最高磁场的试剂或试剂组合。然后，使用相同的细胞系在裸鼠中诱导原发性和转移性前列腺肿瘤，并使用 MRI 和 SQUID 检测来确定这些静脉注射药物在体内定位和识别疾病的敏感性和特异性。拟议的工作将为我们的下一个目标提供所需的全面了解：通过 MRI 和 SQUID 成像对这些药物进行人类原发性和转移性前列腺癌的检测和分期的临床试验。通俗术语：我们的目标是开发一种对前列腺肿瘤进行成像并使用 MRI 确定它们是良性还是癌性的方法。所提出的方法比针吸活检更准确且侵入性更小。