Hornung R, Major A L, McHale M, Liaw L H, Sabiniano L A, Tromberg B J, Berns M W, Tadir Y
Beckman Laser Institute and Medical Clinic, University of California Irvine 92612, USA.
J Am Assoc Gynecol Laparosc. 1998 May;5(2):141-8. doi: 10.1016/s1074-3804(98)80080-7.
To determine the feasibility of macroscopic visualization of small ovarian cancer metastases in vivo by fluorescence after intravenous administration of 5-aminolevulinic acid (ALA); to assess the time after drug injection when fluorescence of small metastases is maximum; and to correlate macroscopic in vivo fluorescence with both microscopic ex vivo fluorescence and histologic findings.
Controlled animal study (Canadian Task Force classification I).
University-based facility.
Twenty-four healthy, female Fischer rats.
Diffuse peritoneal metastatic cancer was induced in Fischer 344 rats by intraperitoneal injection of 1 million syngeneic ovarian cancer cells (NuTu-19). Four weeks after induction ALA100 mg/kg was injected intravenously, and diagnostic laparotomy was performed 1, 3, 6, or 9 hours thereafter.
The peritoneal cavity was illuminated with the Wood's lamp (ultraviolet light). Fluorescence was determined by direct visualization and compared with a calibrated fluorescent disk. Tissues were collected, sectioned, and examined by fluorescence and conventional light microscopy. Within 1 to 3 hours after intravenous injection of ALA, in vivo fluorescence of tumor nodules (diameter 0.4-5.0 mm) was macroscopically visible. Tumor-free peritoneum did not show fluorescence and was significantly distinguishable from cancer nodules. Fluorescence from intestinal tissues was comparable with tumor nodules. Microscopic fluorescence analysis showed similar values for tumor nodules and peritoneum. Stained histologic specimens of peritoneal surface revealed a superficial layer of cancer cells responsible for fluorescence. The time course of the fluorescence curve in the intestine peaked twice, at 1 and 6 hours after ALA injection. Macroscopically fluorescing nodules were histology confirmed as malignant.
Fluorescence detection of small cancer nodules after intravenous injection of ALA is feasible for nodules smaller than 0.5 mm on the peritoneum. One to 3 hours after drug injection is optimal for diagnosis of metastases.
确定静脉注射5-氨基酮戊酸（ALA）后通过荧光在体内宏观可视化小的卵巢癌转移灶的可行性；评估药物注射后小转移灶荧光最强的时间；并将体内宏观荧光与体外微观荧光及组织学结果相关联。
对照动物研究（加拿大工作组分类I）。
大学附属机构。
24只健康雌性Fischer大鼠。
通过腹腔注射100万个同基因卵巢癌细胞（NuTu-19）在Fischer 344大鼠中诱导弥漫性腹膜转移性癌。诱导后4周，静脉注射100mg/kg ALA，此后1、3、6或9小时进行诊断性剖腹术。
用伍德灯（紫外线）照射腹腔。通过直接观察确定荧光，并与校准的荧光盘进行比较。收集组织，切片，并通过荧光显微镜和传统光学显微镜检查。静脉注射ALA后1至3小时内，肿瘤结节（直径0.4 - 5.0mm）的体内荧光在宏观上可见。无肿瘤的腹膜未显示荧光，与癌结节有明显区别。肠道组织的荧光与肿瘤结节相当。微观荧光分析显示肿瘤结节和腹膜的荧光值相似。腹膜表面的染色组织学标本显示表层癌细胞是荧光的来源。肠道荧光曲线的时间进程在ALA注射后1小时和6小时出现两个峰值。宏观上发荧光的结节经组织学证实为恶性。
静脉注射ALA后对腹膜上小于0.5mm的小癌结节进行荧光检测是可行的。药物注射后1至3小时是诊断转移灶的最佳时间。
