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对抗癌症的方法。然而，为了确定新的和有前途的化学预防药物/方案，目前评估治疗效果的方法在很大程度上依赖于侵入性组织活检或后期终点（例如，肿瘤发生率或大小的减少）。目前的方法会给病人带来很大的痛苦，或者需要长期的临床试验。在化学预防治疗期间，尤其难以使用这些方法进行早期、及时和频繁的评估。我们最近的研究表明，一种新开发的光学成像技术具有巨大的潜力，可以通过观察上皮细胞核形态的细微变化来实时、无创地检测癌症。这项技术从未应用于癌症的化学预防。在本研究中，我们的假设是，治疗效果和对口腔癌化学预防的反应可以在侵入性组织活检或治疗结束时获得肿瘤发生率结果之前通过核成像进行监测和预测。我们将通过建立组织“成像分级”，然后预测类视黄酸化学预防的效果，在仓鼠模型的颊袋中验证我们的假设。我们的具体目标是：(1)通过比较口腔癌前病变不同发展阶段的成像数据和随后的组织活检结果来表征和完善这种成像技术，以建立核成像分级；(2)在用维甲酸进行为期7周的口腔癌化学预防疗程结束前，确定该影像学在无创评估和预测治疗效果方面的能力。这是第一个建立这种上皮成像分类并使用成像结果监测和预测癌症化学预防的研究。如果这项研究成功，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，这将对未来开发新的和改进的癌症化学预防药物和策略产生重大影响。

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.