Intraoperative Molecular Imaging Combined With Positron Emission Tomography Improves Surgical Management of Peripheral Malignant Pulmonary Nodules

Abstract

Objective: To determine if intraoperative molecular imaging (IMI) can improve detection of malignant pulmonary nodules.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: These data suggest that combining IMI with PET may provide superior oncologic outcomes for patients with resectable lung cancer.

Figure 1:

Representative example of malignant pulmonary nodule with in vivo fluorescence. Subject 43 presented with a PET avid (SUV=3.0) 1.3cm right upper lobe nodule. At the time of resection, the tumor displayed strong in vivo fluorescence with a TBR of 3.4. Pathologic review demonstrated pulmonary adenocarcinoma with upregulation of the FRα by immunohistochemistry.

Figure 2:

IMI with OTL38 identifies synchronous pulmonary nodules. (a) Subject 37 is a representative subject in which IMI with OTL38 identified an otherwise undetectable malignant pulmonary nodule. Subject presented with a 6.3cm FDG-avid (SUV=6.2) pulmonary adenocarcinoma of the left upper lobe. At the time of resection, IMI identified a 0.8cm synchronous left lower lobe adenocarcinoma. Identification of left lower lobe disease upstaged the subject and resulted in a change of operative plan and postoperative adjuvant therapy course (see Table 3). Bar graphs comparing (b) size and (c) fluorescence of synchronous nodules to fluorescent pulmonary nodules discovered preoperatively. ns-not significant. * p<0.01

Figure 3:

Subject 41, a 71-year-old female presented with a 2.0cm FDG-avid (SUV8.6) located in her left upper lobe. During resection, three areas of fluorescence were noted in her left lower lobe. Wedge biopsy of all left lower lobe lesions revealed adenocarcinoma. These findings upstaged the patient and changed both the operative plan and the postoperative adjuvant treatment (see Table 3).