Evaluation of 111In-DTPA-folate as a receptor-targeted diagnostic agent for ovarian cancer: initial clinical results.
Evaluation of 111In-DTPA-folate as a receptor-targeted diagnostic agent for ovarian cancer: initial clinical results.
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发表时间：
2003-05
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通讯作者：
B. Siegel;F. Dehdashti;D. Mutch;D. Podoloff;R. Wendt;G. Sutton;R. Burt;P. Ellis;C. J. Mathias;M. Green;D. Gershenson
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作者：
B. Siegel;F. Dehdashti;D. Mutch;D. Podoloff;R. Wendt;G. Sutton;R. Burt;P. Ellis;C. J. Mathias;M. Green;D. Gershenson
未标记的细胞膜叶酸受体是肿瘤选择性药物递送的潜在分子靶点，包括用于诊断成像的放射性标记的叶酸螯合物缀合物。我们在这里报告的初步临床研究，这样的代理商，（111）在-二乙烯三胺五乙酸（DTPA）-叶酸，评价卵巢恶性肿瘤的诊断。方法：35名妇女参加了I/II期临床研究，其中33名完成了研究方案所要求的手术随访，以确定疾病状态。患者患有病理证实的恶性肿瘤或因疑似新发卵巢癌（n = 26）、复发性卵巢癌（n = 5）或子宫内膜癌（n = 2）而计划手术。（111）静脉推注In-DTPA-叶酸，在注射后30分钟、4小时和（前19名患者）24小时获得全身图像;在延迟成像时间也进行SPECT。对于19名患者，在给予（111）In-DTPA-叶酸之前注射未标记的游离叶酸，以评估叶酸负荷对示踪剂生物分布的影响。由2名核医学医师对图像进行掩蔽和非掩蔽读数，并与手术后的病理结果进行比较。结果33例手术患者中，14例为新发或复发恶性肿瘤。所有7例新诊断的卵巢癌均由两名盲法阅片者识别（敏感性，100%）。7个复发性恶性肿瘤的检测灵敏度为38%的掩蔽读数和85%的非掩蔽读数，这表明与解剖成像研究（CT）的相关性是非常重要的，在这些病变的诊断。18例研究患者被发现有良性肿块;对于这一有限的人群，（111）In-DTPA-叶酸造影的特异性为76%和82%的掩蔽和非掩蔽的分析，分别。结论（111）In-DTPA-Folate是一种安全、有效的鉴别诊断卵巢良恶性肿块的方法。
UNLABELLED The cell-membrane folate receptor is a potential molecular target for tumor-selective drug delivery, including radiolabeled folate-chelate conjugates for diagnostic imaging. We report here the initial clinical study of such an agent, (111)In-diethylenetriaminepentaacetic acid (DTPA)-folate, evaluated for diagnosis of ovarian malignancy. METHODS Thirty-five women were enrolled in a phase I/II clinical study, with 33 completing the surgical follow-up required by the study protocol for definition of disease status. Patients either had a pathologically proven malignancy or were scheduled for surgery for suspected new ovarian cancer (n = 26), recurrent ovarian cancer (n = 5), or endometrial cancer (n = 2). (111)In-DTPA-folate was administered as an intravenous bolus, and whole-body images were obtained at 30 min, 4 h, and (for the first 19 patients) 24 h after injection; SPECT also was done at the delayed imaging times. For 19 of the patients, unlabeled free folic acid was injected before administration of (111)In-DTPA-folate to also assess the impact of folate loading on tracer biodistribution. Masked and unmasked readings of the images by 2 nuclear medicine physicians were compared with the pathologic findings after surgery. RESULTS Among 33 patients who had surgical intervention, 14 had new or recurrent malignant tumors. All of 7 newly diagnosed ovarian carcinomas were identified by both masked readers (sensitivity, 100%). The sensitivity for detection of 7 recurrent malignancies was 38% for masked readings and 85% for unmasked readings, indicating that correlation with anatomic imaging studies (CT) was highly important in diagnosis of these lesions. Eighteen of the studied patients were found to have benign masses; for this limited population, the specificity of (111)In-DTPA-folate scintigraphy was 76% and 82% for the masked and unmasked analyses, respectively. CONCLUSION (111)In-DTPA-folate is safe, and possibly effective, for scintigraphy differentiating between malignant and benign ovarian masses.