Predina Jarrod D, Newton Andrew D, Keating Jane, Barbosa Eduardo M, Okusanya Olugbenga, Xia Leilei, Dunbar Ashley, Connolly Courtney, Baldassari Michael P, Mizelle Jack, Delikatny Edward J, Kucharczuk John C, Deshpande Charuhas, Kularatne Sumith A, Low Phillip, Drebin Jeffrey, Singhal Sunil
*Center for Precision Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA †Division of Thoracic Surgery, Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA ‡Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA §Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA ¶Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA ||Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania, Philadelphia, PA **Department of Chemistry, and Purdue Institute for Drug Discovery, Purdue University, West Lafayette, IN ††On Target Laboratories, West Lafayette, IN.
Ann Surg. 2017 Sep;266(3):479-488. doi: 10.1097/SLA.0000000000002382.
To determine if intraoperative molecular imaging (IMI) can improve detection of malignant pulmonary nodules.
18-Fluorodeoxyglucose positron emission tomography (PET) is commonly utilized in preoperative assessment of patients with solid malignancies; however, false negatives and false positives remain major limitations. Using patients with pulmonary nodules as a study model, we hypothesized that IMI with a folate receptor targeted near-infrared contrast agent (OTL38) can improve malignant pulmonary nodule identification when combined with PET.
Fifty patients with pulmonary nodules with imaging features suspicious for malignancy underwent preoperative PET. Patients then received OTL38 before pulmonary resection. During resection, IMI was utilized to evaluate known pulmonary nodules and identify synchronous lesions. Tumor size, PET standardized uptake value, and IMI tumor-to-background ratios were compared for known and synchronous nodules via paired and unpaired t tests, when appropriate. Test characteristics of PET and IMI with OTL38 were compared.
IMI identified 56 of 59 (94.9%) malignant pulmonary nodules identified by preoperative imaging. IMI located an additional 9 malignant lesions not identified preoperatively. Nodules only detected by IMI were smaller than nodules detected preoperatively (0.5 vs 2.4 cm; P < 0.01), but displayed similar fluorescence (tumor-to-background ratio 3.3 and 3.1; P = 0.50). Sensitivity of IMI and PET were 95.6% and 73.5% (P = 0.001), respectively; and positive predictive values were 94.2% and 89.3%, respectively (P > 0.05). Additionally, utilization of IMI clinically upstaged 6 (12%) subjects and improved management of 15 (30%) subjects.
These data suggest that combining IMI with PET may provide superior oncologic outcomes for patients with resectable lung cancer.
确定术中分子成像(IMI)能否改善恶性肺结节的检测。
18-氟脱氧葡萄糖正电子发射断层扫描(PET)常用于实体恶性肿瘤患者的术前评估;然而,假阴性和假阳性仍然是主要局限性。以肺结节患者作为研究模型,我们假设使用叶酸受体靶向近红外造影剂(OTL38)的IMI与PET联合应用时可改善恶性肺结节的识别。
50例具有可疑恶性影像学特征的肺结节患者接受术前PET检查。然后患者在肺切除术前接受OTL38。在切除过程中,使用IMI评估已知的肺结节并识别同步病变。对于已知结节和同步结节,在适当情况下通过配对和非配对t检验比较肿瘤大小、PET标准化摄取值和IMI肿瘤与背景比值。比较PET和IMI联合OTL38的检测特征。
IMI识别出术前影像学检查发现的59个恶性肺结节中的56个(94.9%)。IMI还发现了另外9个术前未发现的恶性病变。仅通过IMI检测到的结节小于术前检测到的结节(0.5对2.4 cm;P<0.01),但显示出相似的荧光(肿瘤与背景比值分别为3.3和3.1;P = 0.50)。IMI和PET的敏感性分别为95.6%和73.5%(P = 0.001);阳性预测值分别为94.2%和89.3%(P>0.05)。此外,IMI的临床应用使6例(12%)患者分期上调,并改善了15例(30%)患者的治疗管理。
这些数据表明,IMI与PET联合应用可能为可切除肺癌患者提供更好的肿瘤治疗效果。