PET to Measure Breast Cancer Bone Metastasis Response

描述（由申请人提供）：骨是乳腺癌常见的转移部位。虽然很少“治愈”乳腺癌，但骨主导型乳腺癌患者的预后比内脏受累患者更好，生存期可能延长。这些患者受益于越来越多的有效疗法;然而，治疗的选择受到难以评估反应的阻碍。我们在回顾性研究中发现，连续FDG PET可以测量骨转移对治疗的反应，FDG摄取随治疗的变化可以预测疾病进展时间（TTP），FDG摄取水平可以预测骨折等肿瘤相关事件（SRE）的可能性。我们也使用18F-氟化物PET来评估肿瘤对邻近转移灶的骨的影响，并且显示从氟化物PET获得的骨转移行为的信息与FDG PET不同并且是其补充。我们现在建议将这些初步研究扩展到一个更大的前瞻性研究，即在接受全身治疗的骨主导型乳腺癌患者中进行FDG和氟化物PET。我们的目的是（1）前瞻性地验证FDG和氟化物PET作为骨转移对治疗反应的指标，并以患者结局为金标准，（2）使用定量FDG PET/MRI组合测量转移部位和邻近骨的体内生物学，CT和氟化物PET的目的是预测骨骼事件的风险，并将PET测量与体外测量的肿瘤特征相关联。活检材料的分析，和（3）使用氟化物PET测量双膦酸盐对骨转换的早期作用，以更好地了解这些药物的体内作用，这些药物几乎普遍用于治疗乳腺癌转移。这些研究的结果将是通过患者结局验证的成像方法，用于在临床试验和临床实践中测量乳腺癌骨转移反应，并指导适当的早期干预以预防骨骼事件。

DESCRIPTION (provided by applicant): Bone is a common site of metastasis for breast cancer. Although rarely "cured" of breast cancer, patients with bone-dominant breast cancer have a more favorable prognosis than patients with visceral involvement and may have prolonged survival. These patients benefit from an increasing array of effective therapies; however, the choice of therapy is hampered by the difficulty of assessing response. We have shown, in retrospective studies, that serial FDG PET can measure bone metastasis response to therapy, that changes in FDG uptake with treatment predict time-to-progression (TTP), and that the level of FDG uptake predicts the likelihood of skeletal-related events (SRE), such as fracture. We have also used 18F-fluoride PET to assess tumor effect on the1 bone adjacent to metastases and have shown that the information gained on bone metastasis behavior from fluoride PET is distinct from and complementary to FDG PET. We now propose to extend these preliminary studies to a larger prospective study of FDG and fluoride PET in patients with bone-dominant breast cancer undergoing systemic therapy. Our aims are (1) to prospectively validate FDG and fluoride PET as measures of bone metastasis response to therapy with patient outcome as the gold standard, (2) to measure the in vivo biology of metastatic sites and adjacent bone using a combination of quantitative FDG PET/CT and fluoride PET with the goal of predicting the risk of a skeletal event and also to relate PET measures to tumor characteristics measured by in vitro assay of biopsy material, and (3) to measure the early effect of bisphosphonates on bone turnover using fluoride PET to better understand the in vivo effect of these agents, which are almost universally used in treating breast cancer metastases. The result of these investigations will be imaging methods, validated by patient outcome, for measuring breast cancer bone metastasis response in clinical trials and clinical practice and for directing appropriate early interventions to prevent skeletal events.