Utilization of Cytalux (Pafolacianine) in Identification of Metastatic Sarcoma post VATs Metastasectomy 

Utilization of Cytalux (Pafolacianine) in Identification of Metastatic Sarcoma post VATs Metastasectomy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Utilization of Cytalux (Pafolacianine) in Identification of Metastatic Sarcoma post VATs Metastasectomy Harsimran Panesar, Emma Lewis, Federico Steiner This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6689261/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 31 Jan, 2026 Read the published version in Journal of Cardiothoracic Surgery → Version 1 posted 11 You are reading this latest preprint version Abstract Background Intraoperative molecular imaging using intravenous Pafolacianine ( Cytalux ) has been reported to improve tumor detection in malignant pulmonary and ovarian lesions. Pafolacianine’s affinity for oncological processes in these specific tissues has aided in the elucidation of adequate margins for diagnostic and therapeutic resections when administered shortly prior to surgical intervention [ 1 ]. The role for Pafolacianine for malignant lesions in other organ systems as well as the time in which Pafolacianine remains bound and fluoroscopically detectable, is unknown. Case Presentation : Presented here is a case of a 27-year-old man found with recurrent malignant Peripheral Nerve Sheath Tumor (MPNST) of the right upper extremity who developed new bilateral lung nodules concerning for metastatic disease. Initially, we performed a laparoscopic left-sided video assisted thoracoscopy (VATS) with perioperative Pafolacianine administration and intra-operative Stryker thoracoscopy. These techniques allowed us to successfully remove his metastatic pulmonary disease with wedge metastasectomy. Incidentally, using the thoracoscopy enabled us to identify his primary tumor within the left antecubital fossa. He was then able to undergo excision of his primary disease on postoperative day six. Since the primary tumor continued to emit a fluoroscopic signal that aided us in resection the cancerous lesion in a heavily scarred field. Conclusion To date, there have been no reported cases of Pafolacianine retention within extra-pulmonary and ovarian tumor cells after an extended period of time. We believe our case demonstrates the prospective application and effectiveness of Pafolacianine in targeting cancer cells by fluorescence-guided scopy. In summary, we theorize that there is a role for Pafolacianine, in tandem with fluorescence-guided thoracoscopy, in identifying malignant lesions regardless of tumor location and timing of drug administration. Pafolacianine (Cytalux) Resection margins Tumor detection Malignant peripheral nerve sheath tumor and Pulmonary metastasis Figures Figure 1 Figure 2 Figure 3 BACKGROUND Fluorescence-guided surgery (FGS) has rapidly evolved as a promising technique that improves intraoperative detection and resection of adequate margins of malignant lesions. In brief, FGS involves intravenous administration of a fluoroscopic contrast agent (i.e., Pafolacianine) just prior to surgical intervention. Intra-operatively, the contrast's ability to absorb near-infrared (NIR) light allows visualization with a fluoroscope overlaying white light images of the same anatomy, highlighting the true margin of resectability [ 2 ]. Historically, without fluorescence-guided surgery techniques, the use of preoperative imaging and limited tactile examination of tumor burden has been subpar in prevention of positive margins. Studies have shown that the margin of positivity rate for the ten most common solid tumors ranges from 5.73-35.0% [ 2 , 3 ], which can be theorized as a statistical inverse to a patient’s prognostic viability. This relationship is due to the inability to visualize microscopic cancer cells and therefore the failure to identify micrometastases. Of note, there are several contrast agents that have been FDA approved for clinical use for oncological detection diagnostics and therapy. Agents such as 5-aminolevulinic acid (5-ALA), indocyanine green (ICG), methylene blue (MB), fluorescein sodium, and Pafolacianine ( Cytalux , OTL38), all bear advantages depending on the patient’s malignancy [ 2 ]. Our agent of choice, Pafolacianine (Target Laboratories, Indiana), uses a folic acid analogue to bind to the patient's cellular folate receptor alphas (FRα), which is expressed at abnormally high levels in lung tumors and other histologies including metastatic ovarian, breast, sarcomas, renal cell carcinoma as demonstrated in prior studies [ 1 ]. Case Presentation Written informed consent for publication of the patient’s clinical course, surgical intervention with intraoperative imaging, and post-operative care was obtained from the patient. A copy of the consent form is available for review by the Editor of this journal. A mid-20s man with known MPNST in the right forearm initially underwent a resection of the sarcoma in St. Lucia in 2021 followed by adjuvant chemoradiation therapy. Two years after initial resection, he developed localized recurrence of right forearm malignancy which was treated with six cycles of neoadjuvant chemotherapy followed by radical resection of the right proximal radius in October of 2023. Pathology at that time revealed undifferentiated spindle cell sarcoma with tumor present at the surgical margin warranting additional chemoradiation. In February 2024, he was found to have metastatic sarcoma disease to the lung and underwent a bilateral VATS metastasectomy in the right middle and left upper lobes. Unfortunately in June 2024, he felt a palpable mass near the proximal portion of his prior right forearm incision. An MRI demonstrated a lesion indicative of sarcoma recurrence in the antecubital fossa. Surveillance chest CT chest revealed a new left lung nodule. He was then scheduled for left VATs wedge metastasectomy. As per protocol, Pafolacianine was injected 2 hours prior to bringing the patient into the OR. Left VATS approach was performed and the lung was imaged using Stryker 1788 fluorescence detection camera and the metastatic lesion was visualized (Fig. 1 ). No other nodules were identified using fluorescence detection nor with palpation. A wedge resection was performed with wide margins. Intraoperative frozen pathology confirmed metastatic disease with sarcoma primary. Six days later, the patient returned for planned staged excision, with the assistance of the orthopedic oncology team, of the recurrent sarcoma in the right antecubital fossa which was found to involve the brachial artery and vein. The prior incision was opened and the brachial artery and proximal median nerve to the tumor were mobilized. Given the radiated field and the significant scar tissue from prior surgery. It was difficult to discern scar tissue from neoplasm. To facilitate identification and extent of tumor, the Stryker 1788 camera was used to image the open surgical field and upon doing so,a strong fluorescent signal was confirmed and successfully localized the tumor (Fig. 2). Distinguishing it from surrounding uninvolved tissue which revealed no signal. The mass appeared to be rising from the biceps muscle and part of the brachialis which were eventually excised with the mass. Frozen sections demonstrated sarcoma and the mass was removed (Fig. 3 ). Discussion We believe this presented case contributes to current literature in several significant ways, particularly, in the context of the use of Pafolacianine in the resection in an extra-pulmonary and ovarian tumor cell. The use of fluorescence detection thoracoscope to localize tumor recurrence within the patient’s right upper extremity was fueled by curiosity and difficult dissection. Intriguingly, we found that Pafolacianine is effective a week after administration. Demonstrating long lasting retention of tumor cells even in the setting of washout of normal surrounding stromal tissue. This finding suggests a potential defining role of Pafolaciamine in tumor detection during staged resections as well as the ability to utilize this technology in unsuspecting tumor primaries. Additionally, it is important to note the advantages of Pafolacianine over other intraoperative molecular imaging modalities. For example, ICG, which binds to albumin, is the most commonly used passive tumor-targeted probe. However, it has varied significantly from case to case range from 67–100% in tumor detection ability [ 2 , 4 , 5 ]. Furthermore, ICG exhibits limitations in detecting the tumor depending on the tumor of origin/location, the extent of surrounding inflammatory tissue, and the amount of ICG injected initially. In addition, the duration of ICG in the tissue bed is at max 24 hours, significantly less than the week duration of Pafolacianines. In all, we feel the use of Pafolacianine to assist with surgical resection represents an integration of advanced imaging technologies in complex oncological surgeries. As presented in the case, the impact of this specific contrast agent for soft tissue tumors can help differentiate cancerous cells from surrounding tissues, especially when inclose proximity to vital structures.. The benefits of Pafolacianine highlighted by this case demonstrated its properties that are highly specific to detect malignant cells but are not overly sensitive to surrounding uninvolved tissue within the surgical field due to immediate washout by normal nonmalignant cells. In principle, utilizing such reliable and reproducible technology improves the likelihood of detection of small tumors and discerning tumor extent especially in patients who have undergone prior surgery and or radiation. This patient’s complex history of local resections and metastatic disease offers insight into the multidisciplinary approach required for managing such cases. This serves as an example for clinicians facing similar challenges and reinforces the importance of using a variety of technology for management. Conclusion This case contributes to the literature by demonstrating the effective use of FSG with Pafolacianine in the resection of metastatic PNST. Demonstrating that Pafolacianine is effective up to a week within the tumor and not specific to tumors of specific origins. It offers insight into the potential for this technology to enhance surgical precision, improved resection outcomes, and contributes to the ongoing effort to optimize surgical oncological resections. The case also highlights the importance of a multidisciplinary approach and the evolving role of advanced imaging in the management of complex malignancies. Declarations ETHICS APPROVAL AND CONSENT TO PARTICIPATE/PUBLICATION: The participant has consented to the submission of the case report to the journal. The signed consent form has been attached. Patient provided informed written and verbal consent for the publication AUTHORS’ CONTRIBUTION: All authors contributed substantially to the conception and design of this manuscript, drafting the work, and revising it critically for important intellectual content. Final approval of the version to be published was given by all authors. All authors confirm no competing interests. Harsimran Panesar and Emma Lewis certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. Federico Steiner has no affiliations with or involvement in any organization. He does accept speaking fees from On Target. FUNDING: There has been no funding provided for this study. This study was not funded by any institution or agency. IRB REVIEW: not required given retrospective study in nature AVAILABILITY OF DATA AND MATERIAL: Data sharing is not applicable to this article as no datasets were generated or analysed during the current study. ACKNOWLEDGEMENT: Jennifer Quiroz, BS; Division of Medical Studies, St. George's University, West Indies, Grenada References Lin JL, Liu SC, Liu TF, Chuang SM, Huang CT, Chen YJ, Lee CC, Chien MN, Hou CJ, Yeh HI, Chiang CE, Hung CL. ELUCIDATE Trial: A Single-Center Randomized Controlled Study. J Am Heart Assoc. 2024 May 7;13(9):e033832. doi: 10.1161/JAHA.123.033832 Zheng Y, Yang H, Wang H, Kang K, Zhang W, Ma G, Du S. Fluorescence-guided surgery in cancer treatment: current status and future perspectives. Ann Transl Med. 2019 Mar;7(Suppl 1):S6. doi: 10.21037/atm.2019.01.26 Orosco RK, Tapia VJ, Califano JA, Clary B, Cohen EEW, Kane C, Lippman SM, Messer K, Molinolo A, Murphy JD, Pang J, Sacco A, Tringale KR, Wallace A, Nguyen QT. Positive Surgical Margins in the 10 Most Common Solid Cancers. Sci Rep. 2018 Apr 9;8(1):5686. doi: 10.1038/s41598-018-23403-5. Britt A M Jansen, Claudia A Bargon, Anne E Huibers, Emily L Postma, Danny A Young-Afat, Helena M Verkooijen, Annemiek Doeksen, Efficacy of indocyanine green fluorescence for the identification of non-palpable breast tumours: systematic review, BJS Open , Volume 7, Issue 5, October 2023, zrad092, https://doi.org/10.1093/bjsopen/zrad092 Ishizawa, T., Fukushima, N., Shibahara, J., Masuda, K., Tamura, S., Aoki, T., Hasegawa, K., Beck, Y., Fukayama, M. and Kokudo, N. (2009), Real-time identification of liver cancers by using indocyanine green fluorescent imaging†. Cancer, 115: 2491-2504. https://doi.org/10.1002/cncr.24291 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 31 Jan, 2026 Read the published version in Journal of Cardiothoracic Surgery → Version 1 posted Editorial decision: Revision requested 24 Sep, 2025 Reviews received at journal 31 Jul, 2025 Reviews received at journal 26 Jul, 2025 Reviews received at journal 24 Jul, 2025 Reviewers agreed at journal 21 Jul, 2025 Reviewers agreed at journal 18 Jul, 2025 Reviewers agreed at journal 16 Jul, 2025 Reviewers invited by journal 15 Jul, 2025 Editor assigned by journal 20 May, 2025 Submission checks completed at journal 20 May, 2025 First submitted to journal 17 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6689261","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":486584864,"identity":"c498fb23-4ab8-4542-9193-834e019b073b","order_by":0,"name":"Harsimran Panesar","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABZUlEQVRIie2RMWvCQBiGTwKX5WLXk5T6Fy4ISUsR/8odgXQRsbg4SLgpXbRdU+iPyCR0iwTMorgWLCUi2A4dIoVSqUgvtdDYxr3QPMN38B3Pvd/dAZCT8wchSaE7LZkDEIkVAiRq88dupoL8AhcdvFUIyVR2wXSrgD2KIY/n8az+UDaAMnhptu2ycT1/jGjn3i7K40H0RtYNIPfmT9/KSfdMx6zf0m550VTdUaDdTC2N0+ECQ9QwtS4hLYBC/Tg1mG9BwPq04PmIqIrjF1yVCgUGGGKkY0QI49iCqQuQyUKKhVITSuVd2dg1txQuOd18KsZqnaHcWUAMRplQdFXhEnMx0jhztinSV4oUpZUFTBTTC4rWKRoGpovq5y67DEoOqlfUQ1JhDhrC9CNPLGm56tOqF/aCKerYVVcOvTh+DQ7KFyNt+dw+YleyI8W/PwMACWV1E0QExJk7e5XkvMyUnJycnH/CB6TOfpNMCa6UAAAAAElFTkSuQmCC","orcid":"","institution":"Morristown Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Harsimran","middleName":"","lastName":"Panesar","suffix":""},{"id":486584866,"identity":"1a384d27-99ce-4e52-bac1-823001bde8a6","order_by":1,"name":"Emma Lewis","email":"","orcid":"","institution":"Morristown Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Emma","middleName":"","lastName":"Lewis","suffix":""},{"id":486584867,"identity":"8c03170a-0b30-42c5-969c-9574f68ab51a","order_by":2,"name":"Federico Steiner","email":"","orcid":"","institution":"Morristown Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Federico","middleName":"","lastName":"Steiner","suffix":""}],"badges":[],"createdAt":"2025-05-18 01:08:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6689261/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6689261/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13019-025-03810-2","type":"published","date":"2026-01-31T15:59:19+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":87318320,"identity":"39732655-5f73-4fa8-9b41-19cfd73f639a","added_by":"auto","created_at":"2025-07-22 16:15:37","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":380826,"visible":true,"origin":"","legend":"\u003cp\u003eLeft upper lobe lung metastatic nodule utilizing Cytalux imaging.\u003c/p\u003e","description":"","filename":"fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6689261/v1/0f6ebf5df2f9c2c56d1df4d3.jpg"},{"id":87318317,"identity":"544e888e-f9d3-4b38-a903-3ed904ab7db5","added_by":"auto","created_at":"2025-07-22 16:15:37","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2153907,"visible":true,"origin":"","legend":"\u003cp\u003eIn vivo detection in right upper extremity utilizing Cytalux imaging.\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6689261/v1/1d9b1b9184aaa3a2d7284daf.jpg"},{"id":87318329,"identity":"527ee1a9-351d-49ee-98b4-2e45eb7fe278","added_by":"auto","created_at":"2025-07-22 16:15:37","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":6658145,"visible":true,"origin":"","legend":"\u003cp\u003eResected tumor ex vivo detection utilizing Cytalux imaging\u003c/p\u003e","description":"","filename":"fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6689261/v1/6dd52046fe7804fb6aa97318.jpg"},{"id":101691547,"identity":"c73115b8-7c42-407d-b45e-317a4f994b8a","added_by":"auto","created_at":"2026-02-02 16:14:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":9487670,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6689261/v1/1dc71fbb-a2e6-46ee-bf59-de5307f349fb.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Utilization of Cytalux (Pafolacianine) in Identification of Metastatic Sarcoma post VATs Metastasectomy ","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eFluorescence-guided surgery (FGS) has rapidly evolved as a promising technique that improves intraoperative detection and resection of adequate margins of malignant lesions. In brief, FGS involves intravenous administration of a fluoroscopic contrast agent (i.e., Pafolacianine) just prior to surgical intervention. Intra-operatively, the contrast's ability to absorb near-infrared (NIR) light allows visualization with a fluoroscope overlaying white light images of the same anatomy, highlighting the true margin of resectability [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Historically, without fluorescence-guided surgery techniques, the use of preoperative imaging and limited tactile examination of tumor burden has been subpar in prevention of positive margins. Studies have shown that the margin of positivity rate for the ten most common solid tumors ranges from 5.73-35.0% [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], which can be theorized as a statistical inverse to a patient\u0026rsquo;s prognostic viability. This relationship is due to the inability to visualize microscopic cancer cells and therefore the failure to identify micrometastases.\u003c/p\u003e\u003cp\u003eOf note, there are several contrast agents that have been FDA approved for clinical use for oncological detection diagnostics and therapy. Agents such as 5-aminolevulinic acid (5-ALA), indocyanine green (ICG), methylene blue (MB), fluorescein sodium, and Pafolacianine (\u003cem\u003eCytalux\u003c/em\u003e, OTL38), all bear advantages depending on the patient\u0026rsquo;s malignancy [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Our agent of choice, Pafolacianine (Target Laboratories, Indiana), uses a folic acid analogue to bind to the patient's cellular folate receptor alphas (FRα), which is expressed at abnormally high levels in lung tumors and other histologies including metastatic ovarian, breast, sarcomas, renal cell carcinoma as demonstrated in prior studies [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eWritten informed consent for publication of the patient\u0026rsquo;s clinical course, surgical intervention with intraoperative imaging, and post-operative care was obtained from the patient. A copy of the consent form is available for review by the Editor of this journal.\u003c/p\u003e\u003cp\u003eA mid-20s man with known MPNST in the right forearm initially underwent a resection of the sarcoma in St. Lucia in 2021 followed by adjuvant chemoradiation therapy. Two years after initial resection, he developed localized recurrence of right forearm malignancy which was treated with six cycles of neoadjuvant chemotherapy followed by radical resection of the right proximal radius in October of 2023. Pathology at that time revealed undifferentiated spindle cell sarcoma with tumor present at the surgical margin warranting additional chemoradiation. In February 2024, he was found to have metastatic sarcoma disease to the lung and underwent a bilateral VATS metastasectomy in the right middle and left upper lobes. Unfortunately in June 2024, he felt a palpable mass near the proximal portion of his prior right forearm incision. An MRI demonstrated a lesion indicative of sarcoma recurrence in the antecubital fossa. Surveillance chest CT chest revealed a new left lung nodule. He was then scheduled for left VATs wedge metastasectomy.\u003c/p\u003e\u003cp\u003eAs per protocol, Pafolacianine was injected 2 hours prior to bringing the patient into the OR. Left VATS approach was performed and the lung was imaged using Stryker 1788 fluorescence detection camera and the metastatic lesion was visualized (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). No other nodules were identified using fluorescence detection nor with palpation. A wedge resection was performed with wide margins. Intraoperative frozen pathology confirmed metastatic disease with sarcoma primary.\u003c/p\u003e\u003cp\u003eSix days later, the patient returned for planned staged excision, with the assistance of the orthopedic oncology team, of the recurrent sarcoma in the right antecubital fossa which was found to involve the brachial artery and vein. The prior incision was opened and the brachial artery and proximal median nerve to the tumor were mobilized. Given the radiated field and the significant scar tissue from prior surgery. It was difficult to discern scar tissue from neoplasm. To facilitate identification and extent of tumor, the Stryker 1788 camera was used to image the open surgical field and upon doing so,a strong fluorescent signal was confirmed and successfully localized the tumor (Fig.\u0026nbsp;2). Distinguishing it from surrounding uninvolved tissue which revealed no signal. The mass appeared to be rising from the biceps muscle and part of the brachialis which were eventually excised with the mass. Frozen sections demonstrated sarcoma and the mass was removed (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe believe this presented case contributes to current literature in several significant ways, particularly, in the context of the use of Pafolacianine in the resection in an extra-pulmonary and ovarian tumor cell. The use of fluorescence detection thoracoscope to localize tumor recurrence within the patient\u0026rsquo;s right upper extremity was fueled by curiosity and difficult dissection. Intriguingly, we found that Pafolacianine is effective a week after administration. Demonstrating long lasting retention of tumor cells even in the setting of washout of normal surrounding stromal tissue. This finding suggests a potential defining role of Pafolaciamine in tumor detection during staged resections as well as the ability to utilize this technology in unsuspecting tumor primaries.\u003c/p\u003e\u003cp\u003eAdditionally, it is important to note the advantages of Pafolacianine over other intraoperative molecular imaging modalities. For example, ICG, which binds to albumin, is the most commonly used passive tumor-targeted probe. However, it has varied significantly from case to case range from 67\u0026ndash;100% in tumor detection ability [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Furthermore, ICG exhibits limitations in detecting the tumor depending on the tumor of origin/location, the extent of surrounding inflammatory tissue, and the amount of ICG injected initially. In addition, the duration of ICG in the tissue bed is at max 24 hours, significantly less than the week duration of Pafolacianines.\u003c/p\u003e\u003cp\u003eIn all, we feel the use of Pafolacianine to assist with surgical resection represents an integration of advanced imaging technologies in complex oncological surgeries. As presented in the case, the impact of this specific contrast agent for soft tissue tumors can help differentiate cancerous cells from surrounding tissues, especially when inclose proximity to vital structures.. The benefits of Pafolacianine highlighted by this case demonstrated its properties that are highly specific to detect malignant cells but are not overly sensitive to surrounding uninvolved tissue within the surgical field due to immediate washout by normal nonmalignant cells. In principle, utilizing such reliable and reproducible technology improves the likelihood of detection of small tumors and discerning tumor extent especially in patients who have undergone prior surgery and or radiation.\u003c/p\u003e\u003cp\u003eThis patient\u0026rsquo;s complex history of local resections and metastatic disease offers insight into the multidisciplinary approach required for managing such cases. This serves as an example for clinicians facing similar challenges and reinforces the importance of using a variety of technology for management.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case contributes to the literature by demonstrating the effective use of FSG with Pafolacianine in the resection of metastatic PNST. Demonstrating that Pafolacianine is effective up to a week within the tumor and not specific to tumors of specific origins. It offers insight into the potential for this technology to enhance surgical precision, improved resection outcomes, and contributes to the ongoing effort to optimize surgical oncological resections. The case also highlights the importance of a multidisciplinary approach and the evolving role of advanced imaging in the management of complex malignancies. \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eETHICS APPROVAL AND CONSENT TO PARTICIPATE/PUBLICATION: \u003c/p\u003e\n\u003cp\u003eThe participant has consented to the submission of the case report to the journal. The signed consent form has been attached. Patient provided informed written and verbal consent for the publication\u003c/p\u003e\n\u003cp\u003eAUTHORS’ CONTRIBUTION:\u003c/p\u003e\n\u003cp\u003eAll authors contributed substantially to the conception and design of this manuscript, drafting the work, and revising it critically for important intellectual content. Final approval of the version to be published was given by all authors. All authors confirm no competing interests. \u003c/p\u003e\n\u003cp\u003eHarsimran Panesar and Emma Lewis certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. Federico Steiner has no affiliations with or involvement in any organization. He does accept speaking fees from On Target. \u003c/p\u003e\n\u003cp\u003eFUNDING: There has been no funding provided for this study. This study was not funded by any institution or agency. \u003c/p\u003e\n\u003cp\u003eIRB REVIEW: not required given retrospective study in nature\u003c/p\u003e\n\u003cp\u003eAVAILABILITY OF DATA AND MATERIAL: Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.\u003c/p\u003e\n\u003cp\u003eACKNOWLEDGEMENT: Jennifer Quiroz, BS; Division of Medical Studies, St. George's University, West Indies, Grenada\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLin JL, Liu SC, Liu TF, Chuang SM, Huang CT, Chen YJ, Lee CC, Chien MN, Hou CJ, Yeh HI, Chiang CE, Hung CL. ELUCIDATE Trial: A Single-Center Randomized Controlled Study. J Am Heart Assoc. 2024 May 7;13(9):e033832. doi: 10.1161/JAHA.123.033832 \u003c/li\u003e\n\u003cli\u003eZheng Y, Yang H, Wang H, Kang K, Zhang W, Ma G, Du S. Fluorescence-guided surgery in cancer treatment: current status and future perspectives. Ann Transl Med. 2019 Mar;7(Suppl 1):S6. doi: 10.21037/atm.2019.01.26 \u003c/li\u003e\n\u003cli\u003eOrosco RK, Tapia VJ, Califano JA, Clary B, Cohen EEW, Kane C, Lippman SM, Messer K, Molinolo A, Murphy JD, Pang J, Sacco A, Tringale KR, Wallace A, Nguyen QT. Positive Surgical Margins in the 10 Most Common Solid Cancers. Sci Rep. 2018 Apr 9;8(1):5686. doi: 10.1038/s41598-018-23403-5. \u003c/li\u003e\n\u003cli\u003eBritt A M Jansen, Claudia A Bargon, Anne E Huibers, Emily L Postma, Danny A Young-Afat, Helena M Verkooijen, Annemiek Doeksen, Efficacy of indocyanine green fluorescence for the identification of non-palpable breast tumours: systematic review, \u003cem\u003eBJS Open\u003c/em\u003e, Volume 7, Issue 5, October 2023, zrad092, https://doi.org/10.1093/bjsopen/zrad092\u003c/li\u003e\n\u003cli\u003eIshizawa, T., Fukushima, N., Shibahara, J., Masuda, K., Tamura, S., Aoki, T., Hasegawa, K., Beck, Y., Fukayama, M. and Kokudo, N. (2009), Real-time identification of liver cancers by using indocyanine green fluorescent imaging\u0026dagger;. Cancer, 115: 2491-2504. https://doi.org/10.1002/cncr.24291\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-cardiothoracic-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jcts","sideBox":"Learn more about [Journal of Cardiothoracic Surgery](http://cardiothoracicsurgery.biomedcentral.com)","snPcode":"13019","submissionUrl":"https://submission.nature.com/new-submission/13019/3","title":"Journal of Cardiothoracic Surgery","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Pafolacianine (Cytalux), Resection margins, Tumor detection, Malignant peripheral nerve sheath tumor, and Pulmonary metastasis","lastPublishedDoi":"10.21203/rs.3.rs-6689261/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6689261/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eIntraoperative molecular imaging using intravenous Pafolacianine (\u003cem\u003eCytalux\u003c/em\u003e) has been reported to improve tumor detection in malignant pulmonary and ovarian lesions. Pafolacianine\u0026rsquo;s affinity for oncological processes in these specific tissues has aided in the elucidation of adequate margins for diagnostic and therapeutic resections when administered shortly prior to surgical intervention [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The role for Pafolacianine for malignant lesions in other organ systems as well as the time in which Pafolacianine remains bound and fluoroscopically detectable, is unknown.\u003c/p\u003e\u003ch2\u003eCase Presentation\u003c/h2\u003e\u003cp\u003e: Presented here is a case of a 27-year-old man found with recurrent malignant Peripheral Nerve Sheath Tumor (MPNST) of the right upper extremity who developed new bilateral lung nodules concerning for metastatic disease. Initially, we performed a laparoscopic left-sided video assisted thoracoscopy (VATS) with perioperative Pafolacianine administration and intra-operative Stryker thoracoscopy. These techniques allowed us to successfully remove his metastatic pulmonary disease with wedge metastasectomy. Incidentally, using the thoracoscopy enabled us to identify his primary tumor within the left antecubital fossa. He was then able to undergo excision of his primary disease on postoperative day six. Since the primary tumor continued to emit a fluoroscopic signal that aided us in resection the cancerous lesion in a heavily scarred field.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eTo date, there have been no reported cases of Pafolacianine retention within extra-pulmonary and ovarian tumor cells after an extended period of time. We believe our case demonstrates the prospective application and effectiveness of Pafolacianine in targeting cancer cells by fluorescence-guided scopy. In summary, we theorize that there is a role for Pafolacianine, in tandem with fluorescence-guided thoracoscopy, in identifying malignant lesions regardless of tumor location and timing of drug administration.\u003c/p\u003e","manuscriptTitle":"Utilization of Cytalux (Pafolacianine) in Identification of Metastatic Sarcoma post VATs Metastasectomy ","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-22 16:15:32","doi":"10.21203/rs.3.rs-6689261/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-09-24T21:17:19+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-31T11:38:54+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-27T03:08:45+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-25T03:22:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"97082692104062687746651695368702906897","date":"2025-07-21T06:38:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"224200262726343935111885269838063814732","date":"2025-07-19T02:36:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"200566647171311006089058526271321262862","date":"2025-07-17T01:18:47+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-15T09:47:29+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-20T11:55:53+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-20T11:51:25+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Cardiothoracic Surgery","date":"2025-05-18T01:02:53+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-cardiothoracic-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jcts","sideBox":"Learn more about [Journal of Cardiothoracic Surgery](http://cardiothoracicsurgery.biomedcentral.com)","snPcode":"13019","submissionUrl":"https://submission.nature.com/new-submission/13019/3","title":"Journal of Cardiothoracic Surgery","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e793e7f5-244d-4aef-bd62-ac6e7db746a1","owner":[],"postedDate":"July 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-02T16:10:44+00:00","versionOfRecord":{"articleIdentity":"rs-6689261","link":"https://doi.org/10.1186/s13019-025-03810-2","journal":{"identity":"journal-of-cardiothoracic-surgery","isVorOnly":false,"title":"Journal of Cardiothoracic Surgery"},"publishedOn":"2026-01-31 15:59:19","publishedOnDateReadable":"January 31st, 2026"},"versionCreatedAt":"2025-07-22 16:15:32","video":"","vorDoi":"10.1186/s13019-025-03810-2","vorDoiUrl":"https://doi.org/10.1186/s13019-025-03810-2","workflowStages":[]},"version":"v1","identity":"rs-6689261","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6689261","identity":"rs-6689261","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}