2012-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/645579摘要：乳房磁振造影(MRI)是一高敏感度之乳癌診斷工具1, 2。而動態顯影磁振造影(DCEMRI)之敏感度很高(95%~100%），但特異度在各研究之差異很大(37%~97%)3-6。在MRI加做質子磁振光譜(1H MRS，proton MRS)結合膽鹼(choline)之測量可增加MRI判讀之特異度至82%-100%3, 7-13。曾有研究指出，較高膽鹼含量之乳癌易表現出較高之組織分級，在DCE MRI亦呈現較明顯之顯影消褪，意謂著膽鹼代謝可能與細胞增生及血管新生有關14, 15。以Proton MRS評估病灶之膽鹼含量，亦被用在監測乳癌對前置化學治療是否有療效，報告顯示膽鹼含量之改變在第一次化療後之24小時內便可偵測出來，早期的膽鹼變化和之後腫瘤大小改變有關，但腫瘤大小之改變要到化療較後期才易偵測出11, 16-22。另外，以proton MRS之水/脂肪比例在乳房之表現，曾被發現和膽鹼含量有相關，但此發現極少被提及18, 23, 24。因此，研究乳癌病灶之水及各類脂肪成份可能是一個待開發而有挑戰性之領域。近年來，已有學者開始嘗試結合18F-FDG正子造影(PET)及MRI來做乳房病灶診斷6, 25,26。Limbriaco26等人針對臨床上性質可疑之病灶，做18F-FDG正子造影及MRI之比較，結果發現18F-FDG正子造影之敏感度80%，特異度為100%; 而MRI之敏感度為95%，特異度為98%。Lim等人報告以平行架設18F-FDG PET /MR來監測乳癌對化療藥物之療效，敏感度為70%，特異度72%，而PET結合MRI可較傳統影像更早期地偵測到化療療效27。然而，18F-FDG並不是對腫瘤特異性高的生物標記，因此，我們需嘗試找出其他具代表性之生物標記。18F-Fluorocholine(氟-18-氟膽鹼，又稱FCH)，是膽鹼系列之物質，以FCH來做正子造影，曾用於診斷攝護腺癌、肝細胞癌、肺細支氣管肺泡癌、腦部腫瘤，其原理是基於惡性腫瘤會有較高之膽鹼代謝; 在偵測肝細胞癌方面，FCH正子造影之敏感度(88-94%)高於18F-FDG正子造影(59-68%) 28-33。FCH正子造影亦曾用於判斷攝護腺癌之臨床分級，可有88%之準確度34。目前尚未有明確的以FCH正子造影於乳癌診斷之應用結果。我們假設FCH正子造影可顯示出和proton MRS之膽鹼有類似的生物特性及機制，故我們欲研究下述幾項主題：1. 對於乳房攝影、超音波可見之病灶，評估並比較以proton MRS或FCH正子造影診斷之敏感度、特異度。2. 探究FCH正子造影之表現是否與proton MRS之膽鹼值有相關性。3. 對於惡性病灶，欲探究proton MRS(膽鹼、水及脂肪成份分析)、FCH正子造影是否和臨床預後之因子有關-即腫瘤之分子標記、臨床分級、組織分級。4. 針對局部晚期乳癌，欲探究proton MRS及FCH正子造影是否能早期有效地監測化療療效，及proton MRS、FCH正子造影何者較敏感。並與腫瘤大小之改變做比照。5. 探究以 FCH 正子造影評估乳癌全身分級之可行性。(參考文獻資料請見研究計畫內容最末)<br> Abstract: Breast MRI is a sensitive modality for breast cancer diagnosis1, 2, and dynamiccontrast-enhanced MRI (DCE MRI) revealed high sensitivity (95-100%) but variablespecificity (37-97%) 3-6. 1H magnetic resonance spectroscopy (proton MRS) as an adjunct toDCE-MRI with analysis of choline peak can increase the MRI specificity to 82-100%3, 7-13.Higher choline level was reported to be associated with higher histologic grade of breastcancer, and higher washout rate on DCE MRI, indicating that choline metabolism may berelated to cell proliferation and angiogenesis14, 15. Choline measurement was also used formonitoring treatment response of breast cancer to neoadjuvant chemotherapy (NAC), with theresponse found as early as 24 hours after the first treatment11, 16-22, which is a more sensitivepredictor than tumor volume change.Additionally, water-to-fat ratio of breast tissue on proton MRS, though seldom reported,showed positive correlation with choline detection18, 23 24. Therefore, investigation of chemicalcomposition of water and lipids in breast cancer on proton MRS will be challenging.In recent years, the application of 18F-FDG PET (positron emission tomography) and MRIfor breast lesion diagnosis was emerging6, 25, 26. Imbriaco et al26 compared the diagnosticperformance of 18F-FDG PET and MRI for suspicious breast lesions, with PET showing asensitivity of 80% and specificity 100%; and MRI revealed a sensitivity of 95% andspecificity of 98%. Lim et al27 studied 18F-FDG PET-CT with MRI to monitor treatmentresponse for breast cancer patients receiving NAC, with a sensitivity 70% and specificity 72%,and can detect the treatment response earlier than conventional imaging.However, 18F-FDG is not tumor specific, and searching for an alternative tracer agent as atumor biomarker is necessary. 18F-Fluorocholine (FCH), a choline analog, was used fordiagnosis of prostate cancer, hepatocellular carcinoma (HCC), bronchioloalveolar carcinoma,brain tumor, since malignant tumors show higher choline metabolites than benign lesions; itwas reported that FCH PET showed higher sensitivity (88-94%) than 18F-FDG PET (59-68%)in detecting HCC28-33. FCH PET was used for staging for prostate cancer, with FCH PET-CTcan provide sufficient information for management with an accuracy of 88%34.However, the application of FCH PET in breast cancer diagnosis has not been reported.We hypothesize that FCH reveals choline metabolic profiles of breast cancers, and shows thesimilar pathophysiological mechanism to choline on proton MRS, and our study goals are:1. To investigate and compare the diagnostic performance of proton MRS and FCH PET forlocalized findings on mammography and breast ultrasound.2. To investigate whether FCH PET findings are correlated with choline signals on protonMRS.3. To evaluate if choline, water and lipid signals on proton MRS, FCH PET are associatedwith factors related to clinical outcome and prognosis- that is, molecular markers, tumorstaging, histologic grade of breast cancers.4. For localized advanced breast cancer, to investigate the treatment response to NAC usingproton MRS and FCH PET, and to evaluate which modality is more sensitive.5. To investigate the usefulness of FCH PET for whole body staging for breast cancerpatients.(The references are listed in the end of “Materials and Methods”.)氟-18-氟膽鹼正子造影質子磁振光譜乳房腫瘤18F-Fluorocholine PETProton MR spectroscopyBreast neoplasms