{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:44:48Z","timestamp":1790117088831,"version":"4.0.1"},"reference-count":50,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health\/National Cancer Institute","award":["R01CA243164 (5R01CA243164-06)"],"award-info":[{"award-number":["R01CA243164 (5R01CA243164-06)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chemophototherapy (CPT) is an emerging cancer treatment that leverages the synergistic effects of photodynamic therapy (PDT) and chemotherapy. This approach utilizes photosensitizers like Porphyrin-Phospholipid (PoP) and combined with chemotherapeutic like Doxorubicin (Dox) to enable light-triggered drug release and targeted tumor destruction. Here, we present the validation of a wide-field laparoscopic spatial frequency domain imaging (SFDI) system in an ovarian cancer model. The system allows quantitative fluorescence imaging to obtain absolute drug concentrations in vivo to obtain the absolute concentrations of PoP and Dox fluorescence by correcting for tissue absorption and scattering effects. Fluorescence imaging revealed a significant reduction (~25%, p &lt; 0.001) in PoP concentration in tumor regions post-illumination, demonstrating PDT-mediated photobleaching. Next, the Dox release experiment showed an increase of ~13 \u00b5g\/mL Dox concentration at the local site. The ability to quantify both PoP and Dox fluorescence concentrations with a laparoscopic system underscores its potential for intraoperative monitoring of CPT efficacy. These findings indicate wide-field laparoscopic SFDI as a promising tool for guiding minimally invasive PDT and targeted drug delivery in preclinical and future clinical settings.<\/jats:p>","DOI":"10.3390\/ijms26125571","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T03:44:58Z","timestamp":1749613498000},"page":"5571","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Quantitative Fluorescence Imaging of Chemophototherapy Drug Pharmacokinetics Using Laparoscopic SFDI"],"prefix":"10.3390","volume":"26","author":[{"given":"Rasel","family":"Ahmmed","sequence":"first","affiliation":[{"name":"Department of Biomedical, Engineering, Stony Brook University, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4064-8699","authenticated-orcid":false,"given":"Elias","family":"Kluiszo","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Engineering, Stony Brook University, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Semra","family":"Aygun-Sunar","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Engineering, Stony Brook University, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Willadsen","sequence":"additional","affiliation":[{"name":"POP Biotechnologies, Buffalo, NY 14228, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilliard L.","family":"Kutscher","sequence":"additional","affiliation":[{"name":"POP Biotechnologies, Buffalo, NY 14228, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9052-884X","authenticated-orcid":false,"given":"Jonathan F.","family":"Lovell","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University at Buffalo, Buffalo, NY 14260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0623-7522","authenticated-orcid":false,"given":"Ulas","family":"Sunar","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Engineering, Stony Brook University, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.pdpdt.2015.07.005","article-title":"Assessment of the specificity of a new folate-targeted photosensitizer for peritoneal metastasis of epithelial ovarian cancer to enable intraperitoneal photodynamic therapy. A preclinical study","volume":"13","author":"Schmitt","year":"2016","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1111\/j.1349-7006.2009.01133.x","article-title":"Multicolor in vivo targeted imaging to guide real-time surgery of HER2-positive micrometastases in a two-tumor coincident model of ovarian cancer","volume":"100","author":"Longmire","year":"2009","journal-title":"Cancer Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/0020-7292(96)02721-X","article-title":"Comparison of CA 125 assays with abdominopelvic computed tomography and transvaginal ultrasound in monitoring of ovarian cancer","volume":"54","author":"Sugiyama","year":"1996","journal-title":"Int. J. Gynecol. Obstet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1006\/gyno.2002.6793","article-title":"Laparoscopic Photodynamic Diagnosis of Ovarian Cancer Using 5-Aminolevulinic Acid in a Rat Model","volume":"87","author":"Chan","year":"2002","journal-title":"Gynecol. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9319","DOI":"10.1158\/0008-5472.CAN-10-1783","article-title":"Synergistic enhancement of carboplatin efficacy with photodynamic therapy in a three-dimensional model for micrometastatic ovarian cancer","volume":"70","author":"Rizvi","year":"2010","journal-title":"Cancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1038\/nm.2472","article-title":"Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-\u03b1 targeting: First in-human results","volume":"17","author":"Themelis","year":"2011","journal-title":"Nat. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1006\/gyno.2001.6246","article-title":"Positive Emission Tomography for Evaluating a Complete Clinical Response in Patients with Ovarian or Peritoneal Carcinoma: Correlation with Second-Look Laparotomy","volume":"82","author":"Rose","year":"2001","journal-title":"Gynecol. Oncol."},{"key":"ref_8","first-page":"106","article-title":"Systemic Treatment-Induced Gastrointestinal Toxicity: Incidence, Clinical Presentation and Management","volume":"25","author":"Boussios","year":"2012","journal-title":"Ann Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.7150\/thno.16183","article-title":"Beyond the Barriers of Light Penetration: Strategies, Perspectives and Possibilities for Photodynamic Therapy","volume":"6","author":"Mallidi","year":"2016","journal-title":"Theranostics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"14969","DOI":"10.1364\/OE.18.014969","article-title":"Monitoring photobleaching and hemodynamic responses to HPPH-mediated photodynamic therapy of head and neck cancer: A case report","volume":"18","author":"Sunar","year":"2010","journal-title":"Opt. Express"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Mo, W., Rohrbach, D.J., and Sunar, U. (2012). Imaging a photodynamic therapy photosensitizer in vivo with a time-gated fluorescence tomography system. J. Biomed. Opt., 17.","DOI":"10.1117\/1.JBO.17.7.071306"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.acra.2013.11.009","article-title":"Mesoscopic Fluorescence Tomography of a Photosensitizer (HPPH) 3D Biodistribution in Skin Cancer","volume":"21","author":"Ozturk","year":"2014","journal-title":"Acad. Radiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"707","DOI":"10.4161\/cbt.28557","article-title":"Pegylated liposomal doxorubicin in the management of ovarian cancer","volume":"15","author":"Staropoli","year":"2014","journal-title":"Cancer Biol. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1364\/BOE.4.000531","article-title":"Quantification of PpIX concentration in basal cell carcinoma and squamous cell carcinoma models using spatial frequency domain imaging","volume":"4","author":"Sunar","year":"2013","journal-title":"Biomed. Opt. Express"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1006\/gyno.1996.4502","article-title":"In VivoFluorescence Detection of Ovarian Cancer in the NuTu-19 Epithelial Ovarian Cancer Animal Model Using 5-Aminolevulinic Acid (ALA)","volume":"66","author":"Major","year":"1997","journal-title":"Gynecol. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Celli, J.P., Rizvi, I., Blanden, A.R., Massodi, I., Glidden, M.D., Pogue, B.W., and Hasan, T. (2014). An imaging-based platform for high-content, quantitative evaluation of therapeutic response in 3D tumour models. Sci. Rep., 4.","DOI":"10.1038\/srep03751"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/nnano.2015.311","article-title":"A photoactivable multi-inhibitor nanoliposome for tumour control and simultaneous inhibition of treatment escape pathways","volume":"11","author":"Spring","year":"2016","journal-title":"Nat. Nanotechnol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wang, S., H\u00fcttmann, G., Scholzen, T., Zhang, Z., Vogel, A., Hasan, T., and Rahmanzadeh, R. (2016). A light-controlled switch after dual targeting of proliferating tumor cells via the membrane receptor EGFR and the nuclear protein Ki-67. Sci. Rep., 6.","DOI":"10.1038\/srep27032"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1038\/sj.bjc.6605436","article-title":"In vivo high-resolution fluorescence microendoscopy for ovarian cancer detection and treatment monitoring","volume":"101","author":"Zhong","year":"2009","journal-title":"Br. J. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1097\/IGC.0000000000000497","article-title":"Fischer 344 Rat: A Preclinical Model for Epithelial Ovarian Cancer Folate-Targeted Therapy","volume":"25","author":"Queniat","year":"2015","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.pdpdt.2011.08.003","article-title":"Photodiagnosis and photodynamic therapy of peritoneal metastasis of ovarian cancer","volume":"9","author":"Guyon","year":"2012","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.addr.2012.09.037","article-title":"Liposomal drug delivery systems: From concept to clinical applications","volume":"65","author":"Allen","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1021\/mp800049w","article-title":"Pharmacokinetics and Biodistribution of Nanoparticles","volume":"5","author":"Li","year":"2008","journal-title":"Mol. Pharm."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kress, J., Rohrbach, D.J., Carter, K.A., Luo, D., Poon, C., Aygun-Sunar, S., Shao, S., Lele, S., Lovell, J.F., and Sunar, U. (2017). A dual-channel endoscope for quantitative imaging, monitoring, and triggering of doxorubicin release from liposomes in living mice. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-15790-y"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Rohrbach, D.J., Carter, K.A., Luo, D., Shao, S., Aygun-Sunar, S., Lovell, J.F., and Sunar, U. (2024). Fluence rate-dependent kinetics of light-triggered liposomal doxorubicin assessed by quantitative fluorescence-based endoscopic probe. bioRxiv.","DOI":"10.1101\/2024.12.29.630668"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3546","DOI":"10.1038\/ncomms4546","article-title":"Porphyrin\u2013phospholipid liposomes permeabilized by near-infrared light","volume":"5","author":"Carter","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.jconrel.2015.11.011","article-title":"Porphyrin-phospholipid liposomes with tunable leakiness","volume":"220","author":"Luo","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Venugopal, V., Park, M., Ashitate, Y., Neacsu, F., Kettenring, F., Frangioni, J.V., Gangadharan, S.P., and Gioux, S. (2013). Design and characterization of an optimized simultaneous color and near-infrared fluorescence rigid endoscopic imaging system. J. Biomed. Opt., 18.","DOI":"10.1117\/1.JBO.18.12.126018"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.jconrel.2009.10.034","article-title":"Non-invasive monitoring of intra-tumor drug concentration and therapeutic response using optical spectroscopy","volume":"142","author":"Palmer","year":"2010","journal-title":"J. Control. Release"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.pdpdt.2007.02.003","article-title":"In vivo quantification of fluorescent molecular markers in real-time: A review to evaluate the performance of five existing methods","volume":"4","author":"Bogaards","year":"2007","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Yang, B., Sharma, M., and Tunnell, J.W. (2013). Attenuation-corrected fluorescence extraction for image-guided surgery in spatial frequency domain. J. Biomed. Opt., 18.","DOI":"10.1117\/1.JBO.18.8.080503"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/lsm.10131","article-title":"A multispectral fluorescence imaging system: Design and initial clinical tests in intra-operative Photofrin-photodynamic therapy of brain tumors","volume":"32","author":"Yang","year":"2003","journal-title":"Lasers Surg. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1002\/lsm.22166","article-title":"Recovery of intrinsic fluorescence from single-point interstitial measurements for quantification of doxorubicin concentration","volume":"45","author":"Baran","year":"2013","journal-title":"Lasers Surg. Med."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kim, A., Khurana, M., Moriyama, Y., and Wilson, B.C. (2010). Quantification of in vivo fluorescence decoupled from the effects of tissue optical properties using fiber-optic spectroscopy measurements. J. Biomed. Opt., 15.","DOI":"10.1117\/1.3523616"},{"key":"ref_35","first-page":"171-86","article-title":"Correction of the Internal Absorption Effect in Fluorescence Emission and Excitation Spectra from Absorbing and Highly Scattering Media: Theory and Experiment","volume":"3","author":"Zhadin","year":"1998","journal-title":"J. Biomed. Opt. April."},{"key":"ref_36","first-page":"520","article-title":"Assessment of Photosensitizer Dosimetry and Tissue Damage Assay for Photodynamic Therapy in Advanced-stage Tumors","volume":"79","author":"Sheng","year":"2004","journal-title":"Photochem. Photobiol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Applegate, M.B., Karrobi, K., Angelo, J.P., Austin, W.M., Tabassum, S.M., Agu\u00e9nounon, E., Tilbury, K., Saager, R.B., Gioux, S., and Roblyer, D.M. (2020). OpenSFDI: An open-source guide for constructing a spatial frequency domain imaging system. J. Biomed. Opt., 25.","DOI":"10.1117\/1.JBO.25.1.016002"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.biomaterials.2015.10.027","article-title":"Doxorubicin encapsulated in stealth liposomes conferred with light-triggered drug release","volume":"75","author":"Luo","year":"2016","journal-title":"Biomaterials"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/1011-1344(93)80131-R","article-title":"Murine pharmacokinetics and antitumor efficacy of the photodynamic sensitizer 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a","volume":"20","author":"Bellnier","year":"1993","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/j.1751-1097.1997.tb01889.x","article-title":"The Mechanism of Photofrin Photobleaching and Its Consequences for Photodynamic Dosimetry","volume":"65","author":"Georgakoudi","year":"1997","journal-title":"Photochem. Photobiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1562\/2006-09-07-RA-1033","article-title":"Photobleaching-based Dosimetry Predicts Deposited Dose in ALA-PpIX PDT of Rodent Esophagus","volume":"83","author":"Sheng","year":"2007","journal-title":"Photochem. Photobiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1007\/BF02765099","article-title":"Implicit and explicit dosimetry in photodynamic therapy: A New paradigm","volume":"12","author":"Wilson","year":"1997","journal-title":"Lasers Med. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/j.ijrobp.2005.11.019","article-title":"Pretreatment photosensitizer dosimetry reduces variation in tumor response","volume":"64","author":"Zhou","year":"2006","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5113","DOI":"10.1364\/BOE.8.005113","article-title":"Real-time endoscopic optical properties imaging","volume":"8","author":"Angelo","year":"2017","journal-title":"Biomed. Opt. Express"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4051","DOI":"10.1364\/BOE.6.004051","article-title":"Real-time, profile-corrected single snapshot imaging of optical properties","volume":"6","author":"Angelo","year":"2015","journal-title":"Biomed. Opt. Express"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Angelo, J., Vargas, C.R., Lee, B.T., Bigio, I.J., and Gioux, S. (2016). Ultrafast optical property map generation using lookup tables. J. Biomed. Opt., 21.","DOI":"10.1117\/1.JBO.21.11.110501"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Cuccia, D.J., Bevilacqua, F., Durkin, A.J., Ayers, F.R., and Tromberg, B.J. (2009). Quantitation and mapping of tissue optical properties using modulated imaging. J. Biomed. Opt., 14.","DOI":"10.1117\/1.3088140"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3546","DOI":"10.1364\/BOE.6.003546","article-title":"Quantitative imaging of light-triggered doxorubicin release","volume":"6","author":"Kress","year":"2015","journal-title":"Biomed. Opt. Express"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3312","DOI":"10.1200\/JCO.2001.19.14.3312","article-title":"Recurrent Epithelial Ovarian Carcinoma: A Randomized Phase III Study of Pegylated Liposomal Doxorubicin Versus Topotecan","volume":"19","author":"Gordon","year":"2001","journal-title":"J. Clin. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1364\/AO.35.001780","article-title":"Fluorescence spectroscopy of tissue: Recovery of intrinsic fluorescence from measured fluorescence","volume":"35","author":"Gardner","year":"1996","journal-title":"Appl. Opt."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5571\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:49:49Z","timestamp":1760032189000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5571"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,11]]},"references-count":50,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26125571"],"URL":"https:\/\/doi.org\/10.3390\/ijms26125571","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,11]]}}}