A Novel Laser Fiberscope for Simultaneous Imaging and Phototherapy of Peripheral Lung Cancer

      Background

      Phototherapy is an alternative treatment for patients with localized non-small cell lung cancer who are unable to undergo surgical resection. However, phototherapy is currently limited to treatment of centrally located lung cancer, with the much larger proportion of peripheral lesions remaining inaccessible. There are also concerns over the accuracy of targeted laser treatment because of the need to exchange visualization and irradiation fibers during therapy, preventing the operator from confirming the final location of the irradiation fiber.

      Methods

      A newly developed parallel-type ultrasmall composite optical fiberscope (Laser-eYe Ultrathin fiberscope [LYU]), which enables simultaneous white-light imaging and phototherapy, was evaluated in preclinical lung cancer models. Three models were used: human lung cancer xenografts (A549) in mice, orthotopic VX2 lung tumors in rabbits, and ex vivo pig lungs into which A549 tumor tissue was transplanted. A multifunctional porphyrin-phospholipid nanoparticle (porphysome) was used as a photosensitizer to evaluate fluorescence-guided photothermal therapy.

      Results

      The LYU’s 0.97 mm diameter and hydrophilic coating allowed easy passage through the working channel of all types of bronchoscopes and controlled guidance of the LYU tip in any desired direction. The LYU could visualize the peripheral bronchus and porphysome-laden peripheral tumors. The LYU could also perform photothermal therapy with simultaneous imaging.

      Conclusions

      The LYU enables simultaneous imaging and phototherapy that allows accurate irradiation of peripheral lung cancers. This new laser device may enable ultraminimally invasive transbronchial treatment of peripheral lung cancer.

      Key Words

      Abbreviations:

      LYU ( Laser-eYe Ultrathin fiberscope), NSCLC ( non-small cell lung cancer), PDT ( photodynamic therapy), PTT ( photothermal therapy)
      To read this article in full you will need to make a payment
      Subscribe to CHEST
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Yasui K.
        • Kanazawa S.
        • Sano Y.
        • et al.
        Thoracic tumors treated with CT-guided radiofrequency ablation: initial experience.
        Radiology. 2004; 231: 850-857
        • Lencioni R.
        • Crocetti L.
        • Cioni R.
        • et al.
        Response to radiofrequency ablation of pulmonary tumours: a prospective, intention-to-treat, multicentre clinical trial (the RAPTURE study).
        Lancet Oncol. 2008; 9: 621-628
        • Timmerman R.D.
        • Hu C.
        • Michalski J.M.
        • et al.
        Long-term results of stereotactic body radiation therapy in medically inoperable stage I non-small cell lung cancer.
        JAMA Oncol. 2018; 4: 1287-1288
        • Lanuti M.
        • Sharma A.
        • Willers H.
        • Digumarthy S.R.
        • Mathisen D.J.
        • Shepard J.A.
        Radiofrequency ablation for stage I non-small cell lung cancer: management of locoregional recurrence.
        Ann Thorac Surg. 2012; 93: 921-927
        • Jin C.S.
        • Lovell J.F.
        • Chen J.
        • Zheng G.
        Ablation of hypoxic tumors with dose-equivalent photothermal, but not photodynamic, therapy using a nanostructured porphyrin assembly.
        ACS Nano. 2013; 7: 2541-2550
        • Bolliger C.T.
        • Sutedja T.G.
        • Strausz J.
        • Freitag L.
        Therapeutic bronchoscopy with immediate effect: laser, electrocautery, argon plasma coagulation and stents.
        Eur Respir J. 2006; 27: 1258-1271
        • Simone 2nd, C.B.
        • Cengel K.A.
        Photodynamic therapy for lung cancer and malignant pleural mesothelioma.
        Semin Oncol. 2014; 41: 820-830
        • Lovell J.F.
        • Jin C.S.
        • Huynh E.
        • et al.
        Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents.
        Nat Mater. 2011; 10: 324-332
        • Kato T.
        • Jin C.S.
        • Ujiie H.
        • et al.
        Nanoparticle targeted folate receptor 1-enhanced photodynamic therapy for lung cancer.
        Lung Cancer. 2017; 113: 59-68
        • Jin C.S.
        • Wada H.
        • Anayama T.
        • et al.
        An integrated nanotechnology-enabled transbronchial image-guided intervention strategy for peripheral lung cancer.
        Cancer Res. 2016; 76: 5870-5880
        • Muhanna N.
        • Cui L.
        • Chan H.
        • et al.
        Multimodal image-guided surgical and photodynamic interventions in head and neck cancer: from primary tumor to metastatic drainage.
        Clin Cancer Res. 2016; 22: 961-970
      1. Kinoshita T, Ujiie H, Chen J, et al. Evaluation of novel imaging devices for nanoparticle-mediated fluorescenceguided lung tumor therapy [published online ahead of print February 8, 2019]. Ann Thorac Surg. https://doi.org/10.1016/j.athoracsur.2019.01.008.

        • Jin C.S.
        • Lovell J.F.
        • Zheng G.
        One minute, sub-one-watt photothermal tumor ablation using porphysomes, intrinsic multifunctional nanovesicles.
        J Vis Exp. 2013; 79: e50536
        • Choi M.J.
        • Guntur S.R.
        • Lee K.I.
        • Paeng D.G.
        • Coleman A.
        A tissue mimicking polyacrylamide hydrogel phantom for visualizing thermal lesions generated by high intensity focused ultrasound.
        Ultrasound Med Biol. 2013; 39: 439-448
        • Anayama T.
        • Nakajima T.
        • Dunne M.
        • et al.
        A novel minimally invasive technique to create a rabbit VX2 lung tumor model for nano-sized image contrast and interventional studies.
        PLoS One. 2013; 8: e67355
        • Baskaran R.
        • Lee J.
        • Yang S.G.
        Clinical development of photodynamic agents and therapeutic applications.
        Biomater Res. 2018; 26: 22-25
        • Oka K.
        • Seki T.
        • Akatsu T.
        • Wakabayashi T.
        • Inui K.
        • Yoshino J.
        Clinical study using novel endoscopic system for measuring size of gastrointestinal lesion.
        World J Gastroenterol. 2014; 20: 4050-4058
        • Shigetomi H.
        • Oka K.
        • Seki T.
        • Kobayashi H.
        Design and preclinical validation of the composite-type optical fiberscope for minimally invasive procedures of intrauterine disease.
        J Minim Invasive Gynecol. 2015; 22: 985-991
        • Kasuya K.
        • Oka K.
        • Soya R.
        • Tsuchiya T.
        • Itoi T.
        • Tsuchida A.
        Photodynamic therapy for biliary tract organ via a novel ultra-small composite optical fiberscope.
        Exp Ther Med. 2017; 14: 4344-4348
        • Oka K.
        • Seki T.
        • Naganawa A.
        • Yamashita H.
        • Kim K.
        • Chiba T.
        The development of a composite-type optical fiberscope system for fetoscopic laser photocoagulation of chorionic plate anastomosing vessels (FLPC).
        Minim Invasive Ther Allied Technol. 2010; 19: 94-99