Pharmacy’s Role in Implementing Pafolacianine for Fluorescence-Guided Lung Cancer Surgery

Incomplete lesion detection remains a key limitation in surgical oncology, often resulting in missed malignancy identification or suboptimal resections. Targeted optical imaging has emerged as a critical adjunct to surgical oncology by enhancing lesion localization, delineating margins, and identifying occult disease that eludes standard white light and palpation.¹

Pafolacianine (Cytalux; On Target Laboratories, Inc), a folate receptor–targeted fluorescent probe, is the first FDA‑approved optical imaging agent and prescription medication specifically indicated for intraoperative identification of malignant lesions in ovarian cancer and malignant or nonmalignant pulmonary lesions in patients with known or suspected cancer in the lungs.² This innovative agent creates a new, highly operationalized medication‑use process where pharmacists, in collaboration with surgeons and perioperative nurses, can directly influence safety, workflow reliability, and clinical outcomes.

Pafolacianine was introduced at AdventHealth Celebration, a 357-bed nonprofit hospital in Florida, in 2024 under the direction of Colleen Gaughan, MD, a board-certified thoracic surgeon with special expertise in minimally invasive surgery, robotic surgery, benign esophageal disease, and thoracic oncology. This article details the pharmacy-led integration of pafolacianine, emphasizing procurement strategy, informatics integration, clinical safeguards, and perioperative coordination.

Understanding Pafolacianine

Pafolacianine is a modified folate molecule conjugated to a near‑infrared fluorescent dye that binds with high affinity (approximately 1 nM) to folate receptor–expressing cells, internalizes via receptor‑mediated endocytosis, and then accumulates intracellularly. When illuminated with 760- to 785-nm light and imaged with an FDA‑cleared near‑infrared system, the agent emits fluorescence at 790 to 815 nm, causing folate receptor–positive tissue to “glow” against the surrounding background.

Pafolacianine is indicated as an adjunct for intraoperative identification of malignant lesions in adult patients with ovarian cancer, malignant pulmonary lesions, and nonmalignant pulmonary lesions in adults with known or suspected lung cancer. The recommended pafolacianine dose is 0.025 mg/kg administered as a 60‑minute intravenous (IV) infusion in 250 mL 5% dextrose.³ For ovarian cancer, infusion occurs 1 to 9 hours before surgery, whereas for lung cancer the administration window extends from 1 to 24 hours preoperatively, offering operational flexibility but also placing demands on pharmacy-operation room coordination.³

Clinical Impact

In a pivotal phase 3 ovarian cancer trial (NCT03180307), pafolacianine detected additional malignant lesions in 26.9% of patients, exceeding the 10% success threshold. Complete R0 resections were achieved in approximately 62% of patients. Fluorescence also highlighted benign lesions, emphasizing the need for intraoperative histopathology.⁴

In ELUCIDATE, another phase 3 trial evaluating pafolacianine in lung surgery (NCT04241315), researchers identified clinically significant primary or synchronous malignant nodules in 24% of patients beyond standard inspection. Fluorescence facilitated localization of lesions up to 38 mm deep (mean 6 mm) and sometimes highlighted benign nodules, illustrating its utility even when pathology is ultimately nonmalignant.⁵

Early postmarketing experience corroborates these findings in real-world practice. In a cohort of 39 patients undergoing minimally invasive resection with intraoperative molecular imaging using pafolacianine, primary lung lesions not visible under white light were localized via fluorescence, and all surgical margins were negative on final pathology, reinforcing pafolacianine’s role as an adjunct that enhances nodule localization and supports parenchymal-sparing surgery.⁶

Role of Pharmacy in Cytalux Implementation

Procurement and Vendor Access

Implementation began by establishing procurement pathways through Cardinal Specialty Pharmacy to ensure access to a limited distribution of the frozen biologic product. Pharmacy leadership worked with supply chain teams to define ordering cadence and establish pafolacianine as a stocked item within the institution’s inventory management system (BD Pyxis Logistics). Par levels were aligned with scheduled thoracic surgery block time to minimize waste while ensuring availability for elective cases and anticipated add-ons.

This early focus on procurement ensured cold-chain continuity, predictable access, and appropriate charge capture before the first clinical dose was administered.

Informatics and Workflow Integration

After establishing procurement, pharmacy informatics led integration across the electronic medication-use infrastructure. Pafolacianine was built as an orderable medication in electronic health records (EHRs; Epic), incorporating correct National Drug Codes, dosing logic, infusion parameters, and administration instructions.

Compounding workflows were integrated into Baxter DoseEdge—the institution’s IV room workflow manager—with embedded preparation instructions, diluent restrictions, and beyond-use dating. Barcode-enabled labels were configured to support bedside scanning and closed-loop medication administration by nursing. This informatics groundwork converted pafolacianine from theoretical therapy into a safely executable order.

Storage and Inventory Control

Pafolacianine is supplied as a frozen, single-dose vial (3.2 mg/1.6 mL) requiring storage at –25 to –15 °C in the original light-protective carton.³ The pharmacy department is responsible for maintaining cold-chain integrity, monitoring refreeze limits, and ensuring compliance with manufacturer handling requirements.

Thawing requires at least 60 minutes at controlled room temperature prior to dilution, necessitating disciplined coordination with preoperative nursing to avoid premature preparation or surgical delays. Once thawed, unused vials may be refrigerated for a single period of up to 30 days and refrozen up to 3 times. After dilution in 5% dextrose, the infusion may be refrigerated for up to 24 hours, with completion required within 3 hours of removal from refrigeration. Light protection is maintained throughout all stages.

Clinical Review and Patient Readiness

Pharmacists perform a structured clinical review to confirm patient readiness and appropriateness for pafolacianine administration. This review includes verification of a negative pregnancy test, confirmation that folate-containing supplements have been held for at least 48 hours, medication reconciliation to assess for potential drug-drug interactions, validation of an up-to-date patient standing weight, and confirmation that premedications are correctly ordered, dosed, and scheduled to be administered 30 minutes prior to pafolacianine infusion. Using the verified standing weight, pharmacists calculate the patient-specific pafolacianine dose (0.025 mg/kg), establishing the exact volume required prior to preparation and serving as a final clinical gatekeeper before the medication-use process proceeds.

In parallel, patient readiness is operationally confirmed through direct communication between the pharmacy operational manager and the thoracic surgery service line coordinator. Scheduled cases are communicated in advance via email, while real-time updates, such as changes in patient readiness, case sequencing, or operating room (OR) timing, are conveyed through direct messaging on Microsoft Teams. This bidirectional communication provides the pharmacy with a definitive green light to proceed with preparation, ensuring the pafolacianine dose is compounded and available within the desired imaging window relative to the planned incision time, while minimizing premature preparation and medication waste.

This step functions as a hard safety checkpoint, ensuring pafolacianine is appropriate for the individual patient before preparation begins.

Preparation and Compounding

Once clinical and operational readiness is confirmed, pafolacianine preparation is initiated. Frozen single-dose vials are removed from the freezer and thawed at controlled room temperature (20-25 °C) in the original light-protective carton for a minimum of 60 minutes prior to dilution.³ Thawing timelines are coordinated with the preoperative team to ensure preparation occurs neither too early, risking expiration, nor too late, which could delay surgery.

The calculated patient-specific drug volume is withdrawn from the vial and diluted into 250 mL of 5% dextrose using a dedicated infusion line as instructed by Baxter DoseEdge, matching the EHR order. Compatibility is limited to 5% dextrose; use of alternative diluents may result in pafolacianine aggregation and increased risk of infusion reactions. The compounded solution should appear light blue-greenish to clear, without visible particulates, and must be protected from light throughout handling.³

Pafolacianine vials that have been thawed but unused may be stored at controlled room temperature for a single period of up to 24 hours or refrigerated at 2 °C to 8 °C for a single period of up to 30 days.³ Vials may be refrozen up to 3 times if within the allowable storage period and should not be used after the third refreeze. Once diluted, the infusion may be refrigerated for up to 24 hours; however, once removed from refrigeration, administration must be completed within 3 hours.³ Standardized pharmacy labeling highlights light-protection requirements, beyond-use dating, and the intended administration window to support safe handoff to nursing and ensure timely delivery for surgery.

Pharmacy Operational Manager Perspective

Question: What were the key operational changes your team implemented to support reliable pafolacianine availability and preparation, and how did you hardwire communication with the OR around timing?

Answer: Primary operational changes within the pharmacy focused on storage optimization, interdepartmental communication, and staff education. To support the fastest possible turnaround time and avoid impacts on OR schedules, we established 2 storage locations for pafolacianine: one under refrigeration for confirmed patient‑specific cases, allowing for rapid compounding on the day of the procedure, and another in the freezer to extend dating and track stock. Both storage conditions followed the manufacturer’s recommendations.

Our team strengthened cross‑department collaboration with clinic staff, providers, and our OR team to proactively identify upcoming cases and the required preparation times. At our site, Microsoft Teams enabled real‑time, flexible communication between all stakeholders, ensuring clear visibility of dose readiness, and supported documentation and auditing.

—Jennifer Gregory, PharmD, operational manager, AdventHealth Celebration, Florida

Administration and Monitoring

Pafolacianine administration requires close coordination across preoperative nursing, anesthesia, pharmacy, and surgery. Infusion-related reactions, including nausea, flushing, abdominal pain, hypersensitivity, and elevated blood pressure, occur in approximately 17% of patients, typically within the first 15 minutes of infusion.³

The pharmacy collaborated with the surgical and nursing teams to establish a standardized premedication protocol consisting of acetaminophen 1000 mg orally, diphenhydramine 25 mg IV, pantoprazole 40 mg IV, and ondansetron 4 mg IV. In addition, guidance was developed for managing infusion-related reactions, including criteria for temporary interruption and symptomatic treatment. Pafolacianine is now administered in the preoperative area on the morning of surgery, eliminating evening admissions and streamlining patient flow.

Nursing Perspective

Question: From a nursing perspective, what practical considerations of patient education, monitoring, and infusion management have been most important when administering pafolacianine?

Answer: Caring for patients receiving pafolacianine can be complex, particularly because they are undergoing invasive procedures, and the medication is new, with limited real-world tolerance data. Close monitoring is essential: Vital signs should be checked every 15 minutes for the first hour of infusion, treating the medication with the same vigilance as a blood transfusion. Gastrointestinal symptoms such as nausea or vomiting should be promptly assessed and managed. Patient education is critical, including counseling on avoiding OTC folic acid and instructing them to immediately report symptoms such as rash, flushing, sweating, chills, or pain.

Logistically, barriers on the Cardiac Stepdown Unit include coordinating premedication orders, Cytalux availability, and timely handoff to the preoperative area. These factors can affect workflow and patient experience, highlighting the importance of communication and planning to ensure the infusion occurs safely and efficiently.”

—Zoey Stanczyk, RN, Cardiac Stepdown Progressive Care Unit, AdventHealth Celebration, Florida

Challenges and Solutions

From a pharmacy operations perspective, early pafolacianine implementation presented several workflow and timing challenges. Initial administration occurred on the Cardiac Stepdown Unit, requiring direct hospital admission the evening prior to surgery and creating inefficiencies related to bed utilization, medication timing, and coordination across multiple care areas. Following internal workflow evaluation and labeling updates that expanded allowable storage conditions, pharmacy collaborated with perioperative leadership to transition pafolacianine administration to the preoperative area, enabling same-day admission and improving patient flow.

Additional pharmacy-specific challenges included aligning compounding and delivery timing with variable OR schedules, minimizing drug waste for delayed or rescheduled cases, and ensuring consistent preparation despite strict thawing, refreeze, and light-protection requirements. During early rollout, pharmacy teams and all stakeholders were supported by a manufacturer clinical representative who served as a technical resource, addressing operational questions and sharing nonpromotional implementation insights from other institutions to inform local workflow design.

These challenges were addressed through the development of a standardized pafolacianine pharmacy playbook, clearly defining responsibilities for notification, thawing, compounding, escalation pathways for schedule changes, and communication handoffs with nursing and the OR. Ongoing postcase review and feedback allowed pharmacy to refine timing strategies and reinforce appropriate interpretation of fluorescence as an adjunct to, rather than a replacement for, surgical judgment.

Future Perspectives

Pafolacianine represents an early example of a growing class of receptor-targeted intraoperative imaging agents that will require deliberate medication-use system design. As similar technologies emerge across breast, colorectal, and pancreatic surgery, pharmacy departments will play a vital role in building and sustaining these workflows, including procurement pathways, inventory controls, informatics integration, and compounding oversight. Unlike traditional perioperative medications, these agents demand tight coordination between drug preparation, imaging technology, and surgical timing, positioning pharmacy as a critical operational hub.

Looking ahead, embedding pharmacists within perioperative governance and oncology service lines will be essential to ensure consistent clinical review, right patient selection, and longitudinal safety monitoring. Pharmacy-led tracking of utilization patterns, adverse events, waste, and real-world outcomes can help define best practices and support scalable adoption of fluorescence-guided surgery as it expands into routine oncologic care.

Conclusion

Pafolacianine demonstrates how targeted imaging can translate molecular oncology into actionable intraoperative decision support. Successful implementation depends on far more than drug availability; it requires a tightly coordinated, pharmacy-led system spanning procurement, informatics, clinical review, preparation, and administration. By embracing this expanded role, pharmacy helps ensure safe adoption of fluorescence-guided surgery today while shaping best practices for future targeted imaging technologies in oncology.

References

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2. Lighting the way to detect tumors during surgery. National Cancer Institute. Updated September 4, 2024. Accessed January 18, 2026. https://www.cancer.gov/research/leading-progress/stories/cytalux

3. Cytalux. Prescribing information. On Target Laboratories; 2025. Accessed January 18, 2026. https://cytaluxhcp.com/wp-content/uploads/2025/08/cytalux-uspi-july-2025.pdf

4. Tanyi JL, Randall LM, Chambers SK, et al. A phase III study of pafolacianine injection (OTL38) for intraoperative imaging of folate receptor-positive ovarian cancer (Study 006). J Clin Oncol. 2023;41(2):276-284. doi:10.1200/JCO.22.00291

5. Sarkaria IS, Martin LW, Rice DC, Blackmon SH, Slade HB, Singhal S; ELUCIDATE Study Group. Pafolacianine for intraoperative molecular imaging of cancer in the lung: the ELUCIDATE trial. J Thorac Cardiovasc Surg. 2023;166(6):e468-e478. doi:10.1016/j.jtcvs.2023.02.025

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