Targeted detection of cancer cells during biopsy allows real-time diagnosis of pulmonary nodules

Gregory T. Kennedy, Feredun S. Azari, Elizabeth Bernstein, Bilal Nadeem, Ashley Chang, Alix Segil, Neil Sullivan, Emmanuel Encarnado, Charuhas Desphande, John C. Kucharczuk, Kaela Leonard, Philip S. Low, Silvia Chen, Aline Criton, Sunil Singhal

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Background: The diagnostic yield of biopsies of solitary pulmonary nodules (SPNs) is low, particularly in sub-solid lesions. We developed a method (NIR-nCLE) to achieve cellular level cancer detection during biopsy by integrating (i) near-infrared (NIR) imaging using a cancer-targeted tracer (pafolacianine), and (ii) a flexible NIR confocal laser endomicroscopy (CLE) system that can fit within a biopsy needle. Our goal was to assess the diagnostic accuracy of NIR-nCLE ex vivo in SPNs. Methods: Twenty patients with SPNs were preoperatively infused with pafolacianine. Following resection, specimens were inspected to identify the lesion of interest. NIR-nCLE imaging followed by tissue biopsy was performed within the lesion and in normal lung tissue. All imaging sequences (n = 115) were scored by 5 blinded raters on the presence of fluorescent cancer cells and compared to diagnoses by a thoracic pathologist. Results: Most lesions (n = 15, 71%) were adenocarcinoma-spectrum malignancies, including 7 ground glass opacities (33%). Mean fluorescence intensity (MFI) by NIR-nCLE for tumor biopsy was 20.6 arbitrary units (A.U.) and mean MFI for normal lung was 6.4 A.U. (p < 0.001). Receiver operating characteristic analysis yielded a high area under the curve for MFI (AUC = 0.951). Blinded raters scored the NIR-nCLE sequences on the presence of fluorescent cancer cells with sensitivity and specificity of 98% and 97%, respectively. Overall diagnostic accuracy was 97%. The inter-observer agreement of the five raters was excellent (κ = 0.95). Conclusions: NIR-nCLE allows sensitive and specific detection of cancer cells in SPNs. This technology has far-reaching implications for diagnostic needle biopsies and intraprocedural decision-making.

Original languageEnglish (US)
Pages (from-to)4194-4204
Number of pages11
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Issue number12
StatePublished - Oct 2022


  • Biopsy
  • NIR-nCLE
  • Pulmonary nodules

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging


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