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使用正电子发射断层扫描对结直肠癌中的细胞增殖进行体内成像。

In vivo imaging of cellular proliferation in colorectal cancer using positron emission tomography.

作者信息

Francis D L, Freeman A, Visvikis D, Costa D C, Luthra S K, Novelli M, Taylor I, Ell P J

机构信息

Institute of Nuclear Medicine, University College Medical School, Middlesex Hospital, London, UK.

出版信息

Gut. 2003 Nov;52(11):1602-6. doi: 10.1136/gut.52.11.1602.

Abstract

BACKGROUND

and aims: Positron emission tomography (PET) using (18)F labelled 2-fluoro-2-deoxy-D-glucose ((18)FDG) is an established imaging tool, although the recent development of a biologically stable thymidine analogue [18F] 3'-deoxy-3-fluorothymidine ((18)FLT) has allowed PET to image cellular proliferation by utilising the salvage pathway of DNA synthesis. In this study, we have compared uptake of (18)FLT and (18)FDG with MIB-1 immunohistochemistry to evaluate the role of PET in quantifying in vivo cellular proliferation in colorectal cancer (CRC).

PATIENTS AND METHODS

Patients with resectable, primary, or recurrent CRC were prospectively studied. Thirteen lesions from 10 patients (five males, five females), median age 68 years (range 54-87), were evaluated. Patients underwent (18)FDG and (18)FLT PET scanning. Tracer uptake within lesions was quantified using standardised uptake values (SUVs). Histopathological examination and MIB-1 immunohistochemistry were performed on all lesions, and proliferation quantified by calculating a labelling index (% of MIB-1 positively stained nuclei within 1500 tumour cells).

RESULTS

Histology confirmed adenocarcinoma in 12 of 13 lesions; the remaining lesion was reactive. All eight extrahepatic lesions were visualised using both (18)FLT and (18)FDG. Three of the five resected liver metastases were also avid for (18)FLT and showed high proliferation, while the remaining two lesions which demonstrated no uptake of (18)FLT had correspondingly very low proliferation. There was a statistically significant positive correlation (r =0.8, p<0.01) between SUVs of the tumours visualised with (18)FLT and the corresponding MIB-1 labelling indices. No such correlation was demonstrated with (18)FDG avid lesions (r =0.4).

CONCLUSIONS

(18)FLT PET correlates with cellular proliferation markers in both primary and metastatic CRC. This technique could provide a mechanism for in vivo grading of malignancy and early prediction of response to adjuvant chemotherapy.

摘要

背景与目的

正电子发射断层扫描(PET)使用(18)F标记的2-氟-2-脱氧-D-葡萄糖((18)FDG)是一种成熟的成像工具,尽管一种生物稳定的胸苷类似物[18F] 3'-脱氧-3-氟胸苷((18)FLT)的最新进展使得PET能够通过利用DNA合成的补救途径对细胞增殖进行成像。在本研究中,我们将(18)FLT和(18)FDG的摄取与MIB-1免疫组织化学进行了比较,以评估PET在量化结直肠癌(CRC)体内细胞增殖中的作用。

患者与方法

对可切除的原发性或复发性CRC患者进行前瞻性研究。评估了10例患者(5例男性,5例女性)的13个病灶,中位年龄68岁(范围54 - 87岁)。患者接受了(18)FDG和(18)FLT PET扫描。使用标准化摄取值(SUVs)对病灶内的示踪剂摄取进行量化。对所有病灶进行组织病理学检查和MIB-1免疫组织化学检查,并通过计算标记指数(1500个肿瘤细胞中MIB-1阳性染色细胞核的百分比)来量化增殖。

结果

组织学证实13个病灶中有12个为腺癌;其余病灶为反应性病变。所有8个肝外病灶在(18)FLT和(18)FDG检查中均显影。5个切除的肝转移灶中有3个对(18)FLT摄取也很明显,且显示出高增殖,而其余2个未摄取(18)FLT的病灶增殖相应非常低。用(18)FLT显影的肿瘤的SUVs与相应的MIB-1标记指数之间存在统计学显著的正相关(r = 0.8,p < 0.01)。(18)FDG摄取明显的病灶未显示出这种相关性(r = 0.4)。

结论

(18)FLT PET与原发性和转移性CRC中的细胞增殖标志物相关。该技术可为恶性肿瘤的体内分级和辅助化疗反应的早期预测提供一种机制。

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