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使用18F-氟米索硝唑正电子发射断层扫描评估人类肾肿瘤中的局部缺氧情况。

Assessing regional hypoxia in human renal tumours using 18F-fluoromisonidazole positron emission tomography.

作者信息

Lawrentschuk Nathan, Poon Aurora M T, Foo Serene S, Putra Lydia G Johns, Murone Carmel, Davis Ian D, Bolton Damien M, Scott Andrew M

机构信息

Department of Surgery, University of Melbourne, Victoria, Australia.

出版信息

BJU Int. 2005 Sep;96(4):540-6. doi: 10.1111/j.1464-410X.2005.05681.x.

DOI:10.1111/j.1464-410X.2005.05681.x
PMID:16104907
Abstract

OBJECTIVE

To assess renal tumours for hypoxic regions using 18F-fluoromisonidazole (18F-FMISO) positron emission tomography (PET), a recognized noninvasive method for detecting hypoxia in tumours, as renal cell carcinoma (RCC) can be potentially cured with nephrectomy but recurrence develops in most patients, who then respond poorly to treatments such as chemotherapy, and hypoxia is known to confer resistance to radiotherapy and chemotherapy in many solid tumours.

PATIENTS AND METHODS

In all, 17 patients had 18F-FMISO PET scans before nephrectomy for presumed RCC. Specimens were examined histologically, and immunohistochemistry was used to compare the microvessel density (MVD) as an indicator of angiogenesis in the tumour and normal parenchyma, in 15 patients. Tumour oxygenation was measured invasively in three patients using a polarographic oxygen sensor probe.

RESULTS

Of the 15 patients with histological results, 11 had RCC and four had other tumours. Although there was a trend there was no statistically significant (P = 0.14) difference in the maximum standardized uptake value (SUV(max)) when comparing the region of the kidney involved with RCC; the mean (95% confidence interval) SUV(max) in the tumours was 1.3 (0.15), whilst that in the normal contralateral kidney was 1.1 (0.22). The MVD was greater in RCC, at 13.7 (3.1) mean vessels per high-power field than in normal tissue, at 6.9 (1.9). Hypoxia as measured polarographically was detected in three RCCs (median pO2 9.6 mmHg) compared to normal parenchyma at 37.6 mmHg.

CONCLUSIONS

Although 18F-FMISO scans showed significant uptake in other solid tumours, there was only mild 18F-FMISO uptake in the present RCCs. The invasive measurements indicated that there was hypoxia in RCC, but the median pO2 did not fall below 9.5 mmHg. Further direct studies of renal tumour oxygenation combined with therapies directed towards hypoxia may allow a better understanding of the relationship between 18F-FMISO results and the biological significance of hypoxia in RCC.

摘要

目的

使用18F-氟米索硝唑(18F-FMISO)正电子发射断层扫描(PET)评估肾肿瘤的缺氧区域,PET是一种公认的检测肿瘤缺氧的非侵入性方法。由于肾细胞癌(RCC)有可能通过肾切除术治愈,但大多数患者会复发,复发后对化疗等治疗反应不佳,且已知缺氧会使许多实体瘤对放疗和化疗产生抗性。

患者与方法

共有17例疑似RCC患者在肾切除术前进行了18F-FMISO PET扫描。对标本进行组织学检查,并对15例患者使用免疫组织化学比较微血管密度(MVD),作为肿瘤和正常实质中血管生成的指标。使用极谱氧传感器探头对3例患者进行了有创肿瘤氧合测量。

结果

在15例有组织学结果的患者中,11例患有RCC,4例患有其他肿瘤。比较RCC累及的肾脏区域时,最大标准化摄取值(SUV(max))虽有趋势但无统计学显著差异(P = 0.14);肿瘤中的平均(95%置信区间)SUV(max)为1.3(0.15),而对侧正常肾脏中的为1.1(0.22)。RCC中的MVD更高,每高倍视野平均血管数为13.7(3.1),而正常组织为6.9(1.9)。与正常实质的37.6 mmHg相比,通过极谱法测量在3例RCC中检测到缺氧(中位pO2为9.6 mmHg)。

结论

尽管18F-FMISO扫描在其他实体瘤中显示出明显摄取,但在目前的RCC中只有轻度的18F-FMISO摄取。有创测量表明RCC中存在缺氧,但中位pO2未降至9.5 mmHg以下。进一步将肾肿瘤氧合与针对缺氧的治疗相结合的直接研究,可能有助于更好地理解18F-FMISO结果与RCC中缺氧的生物学意义之间的关系。

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