Imaging Evaluation of Cancer Chemoprevention

描述(由申请人提供)：癌症化学预防是一种很有前途的抗癌方法。然而，目前评估治疗效果的方法，以确定新的和有前景的化学预防药物/方案，在很大程度上取决于侵入性组织活检或后来的终点(例如，减少肿瘤发病率或大小)。目前的方法会给患者带来巨大的痛苦，或者需要进行长期的临床试验。在化学预防治疗期间，使用这些方法进行早期、及时和频繁的评估尤其困难。我们最近的研究表明，一种新开发的光学成像技术通过观察上皮细胞核形态的细微变化，在实时、非侵入性癌症检测方面具有巨大的潜力。这项技术从未被应用于癌症的化学预防。在这项拟议的研究中，我们的假设是，在I治疗结束时获得有创性组织活检或肿瘤发病结果之前，可以通过核成像来监测和预测治疗效果和对口腔癌化学预防的反应。我们将在仓鼠模型的面颊囊中验证我们的假设，方法是建立组织成像分级，然后预测维甲酸化学预防的效果。我们的具体目标是(1)通过将成像数据与口腔癌前病变不同发展阶段的后续组织活检结果进行比较来表征和改进这种成像技术，以建立核成像分级；以及(2)在用维甲酸进行为期7周的口腔癌化学预防疗程结束之前，确定这种成像用于非侵入性评估和预测治疗效果的能力。这是第一次建立这种上皮成像分类并将成像结果用于监测和预测癌症化学预防的研究。这项拟议的研究如果成功，将为癌症化学预防过程中的治疗监测提供一个理想的客观工具，这将对未来新的和改进的癌症化学预防药物和策略的发展产生重大影响。

DESCRIPTION (provided by applicant): Cancer chemoprevention is a promising approach to fighting cancers. However, current methods to evaluate treatment efficacy, in order to identify new and promising chemopreventive agents/regimes, largely depend on invasive tissue biopsy or later endpoints (e.g., reduction of tumor incidence or size). Current methods entail significant distress to patients or require a long term clinical trial. It is particularly difficult to use these approaches for early, timely, and frequent evaluation during the chemoprevention treatment period. Our recent studies indicate that a newly-developed optic imaging technology has great potential for real-time, noninvasive cancer detection by observing subtle alterations in the nuclear morphology of epithelial cells. This technology has never been applied to cancer chemoprevention. In this proposed study, our hypothesis is that the treatment efficacy and response to oral cancer chemoprevention can be monitored and predicted with nuclear imaging prior to invasive tissue biopsy or tumor incidence outcome obtained at the end of the i treatment. We will test our hypothesis in the cheek pouches of a hamster model by establishing tissue "imaging grading" and then predicting the efficacy of retinoid acid chemoprevention. Our specific aims are (1) to characterize and refine this imaging technique by comparing the imaging data with subsequent tissue biopsy results from different developmental stages of oral premalignant lesions to establish nuclear imaging grading; and (2) to determine the capacity of this imaging for noninvasive evaluation and predication of treatment efficacy before the end of a 7-week course of oral cancer chemoprevention with retinoic acid. This is the first study to establish such epithelial imaging classification and use the imaging findings for monitoring and predication of cancer chemoprevention. This proposed study, if successful, will provide an ideal objective tool for treatment monitoring during cancer chemoprevention that will have significant impact on future development of new and improved cancer chemoprevention agents and strategies.