利用乳腺癌淋巴結(jié)轉(zhuǎn)移中高度表達(dá)的兩個(gè)細(xì)胞表面標(biāo)志物，Moffitt癌癥中心的研究人員與其他研究院的同事一起工作,，開發(fā)出定向熒光分子成像探針,，它能非侵襲性地檢測乳腺癌的淋巴結(jié)轉(zhuǎn)移。新程序可以降低乳腺癌病人侵襲性與不可靠的哨兵淋巴結(jié)（SLN）活組織檢查和手術(shù)相關(guān)的陰性副作用,。
他們的研究發(fā)表在Clinical Cancer Research上,，這是美國癌癥研究協(xié)會(huì)的公開出版物。
高達(dá)74%的乳腺癌患者都經(jīng)歷過哨兵淋巴結(jié)活檢,，結(jié)果發(fā)現(xiàn)腋窩淋巴結(jié)或前淋巴結(jié)轉(zhuǎn)移是陰性的,，通訊作者David L. Morse博士說，他是Moffitt研究所的副會(huì)員,，其研究領(lǐng)域包括實(shí)驗(yàn)治療與診斷成像,，"測定前淋巴結(jié)轉(zhuǎn)移的存在與否對于乳腺癌分期與預(yù)后很關(guān)鍵。因?yàn)樯诒馨徒Y(jié)活檢的不可靠性和潛在的副作用,，迫切需要一種非侵襲性的,、更精確的方法來評估淋巴結(jié)參與乳腺癌的轉(zhuǎn)移。"
作者指出,，哨兵淋巴結(jié)活檢的術(shù)后并發(fā)癥包括淋巴水腫,、血清腫形成、感覺神經(jīng)損傷和病人活動(dòng)范圍受限,。此外,，腋窩淋巴結(jié)活檢不能確定5%-10%患者的疾病。
在開發(fā)識別乳腺癌腋窩淋巴結(jié)轉(zhuǎn)移的靶向分子探針中,，來自Moffitt研究所,、亞利桑那大學(xué)和佛羅里達(dá)大學(xué)的研究小組利用了2個(gè)細(xì)胞表面標(biāo)志物--CAIX 和CAXII。CAIX是一種細(xì)胞表面標(biāo)志物,， "在乳腺癌淋巴結(jié)轉(zhuǎn)移中高度,、廣泛表達(dá)"，在正常組織中不表達(dá),。
Morse 解釋說,，CAIX 和CAXII兩者都是完全的質(zhì)膜蛋白伴有較大的細(xì)胞外組分,，這些細(xì)胞外組分很容易與靶向成像探針接觸并結(jié)合。另外,，一些研究表明,，CAIX表達(dá)是與負(fù)性預(yù)后、抗化療和放射治療乳腺癌相關(guān),。CAXII是一種在超過75%的腋窩淋巴結(jié)轉(zhuǎn)移患者中表達(dá)的蛋白,。
研究人員接著通過使用特異性地與CAIX 和CAXII結(jié)合的單克隆抗體開發(fā)了他們的靶向試劑，CAIX 和CAXII都已知能促進(jìn)腫瘤的生長,。
研究人員稱,，已經(jīng)對許多評估前哨淋巴結(jié)的無創(chuàng)光學(xué)成像程序進(jìn)行了調(diào)查研究，但是這些評估方法缺乏靶向腫瘤轉(zhuǎn)移標(biāo)志物的能力,。
"這些方法只提供了解剖學(xué)圖形,，沒有檢測存在于淋巴結(jié)的腫瘤細(xì)胞"，Morse這樣解釋,，"使用小鼠乳腺癌轉(zhuǎn)移模型和一種新的,、基于單克隆抗體的分子成像劑，我們開發(fā)出了利用熒光成像檢測ALN轉(zhuǎn)移的一種定向的,、非侵襲性方法",。
除了用小鼠的成像研究外，研究人員也報(bào)道了,，聯(lián)合CAIX 和CAXII對組織微陣列（TMA）研究中患者損贈(zèng)的樣本進(jìn)行檢測,，結(jié)果達(dá)到了100%的符合率。
"在ALNs中檢測腫瘤細(xì)胞的成像探針具有高靈敏度",， Morse解釋說,，"無論是CAIX 還是CAXII,，均表達(dá)于該項(xiàng)研究中所調(diào)查的100%的乳腺癌淋巴結(jié)轉(zhuǎn)移樣本中,。這些成像探針有望在臨床中對乳腺癌進(jìn)行分期提供一種非侵入性檢測方式，它沒有進(jìn)行一些不必要的昂貴的手術(shù),。"（生物谷bioon.com）
doi:10.1158/1078-0432.CCR-11-0238
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PMID:
Noninvasive Detection of Breast Cancer Lymph Node Metastasis Using Carbonic Anhydrases IX and XII Targeted Imaging Probes
Narges K. Tafreshi, Marilyn M. Bui, Kellsey Bishop, Mark C. Lloyd, Steven A. Enkemann, Alexis S. Lopez, Dominique Abrahams, Bradford W. Carter, Josef Vagner, Stephen R. Gobmyer, Robert J. Gillies, and David L. Morse
Abstract Purpose: To develop targeted molecular imaging probes for the noninvasive detection of breast cancer lymph node metastasis. Experimental Design: Six cell surface or secreted markers were identified by expression profiling and from the literature as being highly expressed in breast cancer lymph node metastases. Two of these markers were cell surface carbonic anhydrase isozymes (CAIX and/or CAXII) and were validated for protein expression by immunohistochemistry of patient tissue samples on a breast cancer tissue microarray containing 47 normal breast tissue samples, 42 ductal carcinoma in situ, 43 invasive ductal carcinomas without metastasis, 46 invasive ductal carcinomas with metastasis, and 49 lymph node macrometastases of breast carcinoma. Targeted probes were developed by conjugation of CAIX- and CAXII-specific monoclonal antibodies to a near-infrared fluorescent dye. Results: Together, these two markers were expressed in 100% of the lymph node metastases surveyed. Selectivity of the imaging probes were confirmed by intravenous injection into nude mice-bearing mammary fat pad tumors of marker-expressing cells and nonexpressing cells or by preinjection of unlabeled antibody. Imaging of lymph node metastases showed that peritumorally injected probes detected nodes harboring metastatic tumor cells. As few as 1,000 cells were detected, as determined by implanting, under ultrasound guidance, a range in number of CAIX- and CAXII-expressing cells into the axillary lymph nodes. Conclusion: These imaging probes have potential for noninvasive staging of breast cancer in the clinic and elimination of unneeded surgery, which is costly and associated with morbidities. Clin Cancer Res; 18(1); 207-19. ?2011 AACR.
