SESORRS endoscopy for the staging and evaluation of colorectal cancer

SESORRS 内窥镜检查用于结直肠癌的分期和评估

基本信息

批准号：
10350171
负责人：
Fay Nicolson
金额：
$ 13.35万
依托单位：
DANA-FARBER CANCER INST
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-08 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10350171
关键词：
3-Dimensional Address Animal Model Area Award Beds Biodistribution Biological Markers Cancer Biology Cause of Death Cell surface Characteristics Chemicals Clinical Collection Colon Colorectal Cancer Contrast Media DNA Sequence Alteration Dana-Farber Cancer Institute Detection Development Diagnosis Dose Drug Kinetics Endoscopes Endoscopy Evaluation Excision Fiber Fiber Optics Goals Histology Image Image Analysis Imaging Techniques KRASG12D Large Intestine Lead Lesion Light Magnetic Resonance Imaging Malignant Neoplasms Membrane Proteins Mentors Microscopic Modeling Molecular Target Morphology Operative Surgical Procedures Optics Outcome Phase Photons Positron-Emission Tomography Principal Investigator Proteins Proteomics Radiochemistry Radiolabeled Raman Spectrum Analysis Reproducibility Research Research Personnel Residual Tumors Residual state Specificity Specimen Staging Surface Testing Tissues Training Tumor Cell Invasion anatomic imaging cancer genetics cancer imaging career clinical practice clinical translation colorectal cancer treatment design experience image guided image processing imaging approach imaging modality imaging probe improved in vivo in vivo optical imaging interest method development migration molecular imaging mouse model neoplastic cell novel optical imaging patient prognosis patient stratification preclinical study radiotracer real-time images screening skills spectroscopic imaging success time use treatment group tumor

项目摘要

PROJECT SUMMARY/ABSTRACT: Colorectal cancer (CRC) is the third most common cancer and a leading cause of death worldwide. The degree of CRC invasion into the large intestinal wall is associated with patient prognosis. White light endoscopy (WLE) is used to evaluate lesions of interest within the colon, however WLE provides only morphological information, often failing to efficiently evaluate the required resection margin or extent of tumor invasion. There is a significant need to develop an endoscopic approach that can address these challenges. We believe this could be achieved using spatially offset Raman spectroscopy (SORS) in combination with surface enhanced resonance Raman scattering (SERRS) contrast agents (CAs). The combination of the two approaches is referred to as surface enhanced spatially offset resonance Raman spectroscopy (SESORRS). In the proposed preclinical study, I will test the hypothesis that SESORRS endoscopy could improve existing practices for the detection, staging and surgical resection of CRC. During the K99 mentored phase, I will build and validate the efficiency of a SORS endoscope using ex vivo phantoms (SA1.1, SA1.2). Using Apcfl/+ and Apcfl/+;KrasG12D/+ mouse models of CRC, we will evaluate the efficiency of SESORRS endoscopy to detect and stage CRC in vivo. Results will be correlated with MRI, PET, and ex vivo histology (SA2.1). The biodistribution and pharmacokinetic profiles of radiolabeled SERRS CAs will be evaluated using PET imaging (SA2.2). As an independent investigator, I will determine the optimal dose of SERRS CAs required for SORS endoscopic imaging of CRC (SA2.3). In SA3 I will determine and validate the advantage of using molecularly targeted-SERRS CAs over non-targeted SERRS CAs, together with the ability of SESORRS endoscopy to assist in the surgical resection of lesions of interest by detecting residual tumor cells on the surface, and beneath, the resection bed. If successful, SESORRS endoscopy could be very useful in the screening, diagnosis, and treatment of CRC. This project will enable us to predict the potential success of clinical SESORRS endoscopy and increase the likelihood of achieving eventual clinical translation. I have a unique set of expertise in SERRS, SORS and SESORRS imaging and believe I am highly qualified to lead, and conduct, the proposed project here at the Dana-Farber Cancer Institute. I also have identified the following key areas which require additional training in order to support my transition to independence: (1) mouse models of CRC; (2) understanding the cancer biology of CRC and the influence of genetic mutations on CRC invasion; (3) radiochemistry and PET imaging and; (4) requirements for clinical translation. I have deliberately chosen and carefully assembled a world-class committee of mentors and advisors including my primary mentor Dr. Kevin Haigis, as well as Dr. Conor L. Evans and Dr. Norman Nishioka who will serve as co-mentors. My mentors are in full support of my research and career goals. I am committed to this award and strongly believe that it will help me gain the necessary training required to enable my long-term career goal of being an established investigator in the field of molecular imaging.

项目概要/摘要：结直肠癌 (CRC) 是全球第三大常见癌症，也是全球死亡的主要原因。学位 CRC 侵入大肠壁的情况与患者预后相关。白光内窥镜检查 (WLE) 用于评估结肠内感兴趣的病变，但 WLE 仅提供形态学信息，通常无法有效评估所需的切除边缘或肿瘤侵袭的程度。有一个显着的需要开发一种可以应对这些挑战的内窥镜方法。我们相信这是可以实现的使用空间偏移拉曼光谱 (SORS) 与表面增强共振拉曼相结合散射（SERRS）造影剂（CA）。这两种方法的结合称为表面增强空间偏移共振拉曼光谱（SESORRS）。在拟议的临床前研究中，我将检验 SESORRS 内窥镜检查可以改进现有的检测、分期和治疗实践的假设手术切除结直肠癌。在 K99 指导阶段，我将构建并验证 SORS 的效率使用离体模型（SA1.1，SA1.2）的内窥镜。使用 Apcfl/+ 和 Apcfl/+;KrasG12D/+ CRC 小鼠模型，我们将评估 SESORRS 内窥镜检查在体内检测和分期 CRC 的效率。结果将是与 MRI、PET 和离体组织学 (SA2.1) 相关。生物分布和药代动力学特征将使用 PET 成像 (SA2.2) 评估放射性标记的 SERRS CA。作为一名独立调查员，我会确定 CRC 的 SORS 内窥镜成像所需的 SERRS CA 的最佳剂量 (SA2.3)。在SA3我将确定并验证使用分子靶向 SERRS CA 相对于非靶向 SERRS 的优势 CA 与 SESORRS 内窥镜的能力一起协助手术切除感兴趣的病变检测切除床表面和下方的残留肿瘤细胞。如果成功，SESORRS 内窥镜检查对于结直肠癌的筛查、诊断和治疗非常有用。这个项目将使我们预测临床 SESORRS 内窥镜检查的潜在成功并增加实现的可能性最终的临床转化。我在 SERRS、SORS 和 SESORRS 成像方面拥有一套独特的专业知识，我相信我非常有资格领导和实施丹纳法伯癌症研究所拟议的项目。我还确定了以下需要额外培训的关键领域，以支持我过渡到独立性：（1）CRC小鼠模型； (2)了解CRC的癌症生物学及其影响 CRC侵袭的基因突变； (3)放射化学和PET成像； (四)临床要求翻译。我精心挑选并精心组建了一个世界级的导师和顾问委员会包括我的主要导师 Kevin Haigis 博士，以及 Conor L. Evans 博士和 Norman Nishioka 博士，他们将担任共同导师。我的导师全力支持我的研究和职业目标。我致力于此奖项并坚信它将帮助我获得实现长期职业生涯所需的必要培训目标是成为分子成像领域的知名研究者。