Preparing Clinical Sites for Radiopharmaceutical Trials: A Comprehensive Guide
The landscape of oncology clinical research is rapidly evolving with the emergence of radiopharmaceutical therapies, also known as radioligand therapy (RLT). These innovative treatments represent a precision medicine approach that uses targeted radiation to treat cancer with a goal of minimizing damage to healthy tissue. However, participating in radiopharmaceutical trials requires significantly different infrastructure, expertise, and operational readiness compared to traditional oncology studies. Sites that want to participate in this growing field must understand and address unique challenges across regulatory compliance, operational capabilities, and cross-functional coordination.
Understanding Radiopharmaceutical Trials
Radiopharmaceutical trials fall into two main categories: diagnostic imaging studies and therapeutic studies. Diagnostic trials use imaging tracers that emit primarily gamma rays to visualize biological activity in the body through PET or SPECT scans. These tracers often have very short half-lives, for example, Gallium-68 has a half-life of just 68 minutes, requiring manufacturing facilities within one to two hours of the clinical site.
Therapeutic radiopharmaceuticals work differently. They emit alpha particles or beta particles designed to damage cancer cells in a targeted manner. Common therapeutic isotopes include Lutetium-177 with a 6.7-day half-life, Actinium-225 with a 10-day half-life, and Yttrium-90 with a 2.67-day half-life. Because of their longer half-lives, these therapeutic agents are typically manufactured at central contract development and manufacturing organizations (CDMOs) and shipped to sites on a just-in-time basis for each patient dose.
Regulatory and Licensing Requirements
The foundation of site readiness begins with proper regulatory authorization. Sites must have active licensure for the receipt, storage, handling, and administration of radioactive materials. This is not a simple checkbox, it requires securing radiation use authorization (RUA) and specific license amendments for each isotope being studied.
One critical lesson from recent trials is that delays in state and Nuclear Regulatory Commission (NRC) review timelines can significantly impact study startup. The regulatory landscape varies by jurisdiction, with some facilities falling under NRC oversight and others under state-specific regulations. Sites should begin the licensing process early, ideally during protocol development, to avoid becoming the bottleneck in study activation.
Compliance extends beyond initial licensing. Sites must validate their adherence to NRC or state-specific radioactive use regulations and confirm they have appropriate waste handling protocols in place, including vendor contracts for radioactive waste disposal. Understanding disposal limitations and having clear plans for waste management is essential, as some facilities may have constraints on the volume or type of radioactive waste they can handle.
Infrastructure and Facility Readiness
Physical infrastructure requirements for radiopharmaceutical trials are substantial. Facilities may need shielded rooms with appropriate ventilation, proper room signage indicating radiation areas, and dedicated toilets for patients who have received radioactive doses. These are not minor renovations, they represent significant capital investments that must be in place before a site can be activated.
Secured storage for radioactive products is mandatory, requiring dedicated spaces that meet regulatory specifications. Sites must also have the appropriate imaging capabilities, with PET or SPECT cameras that meet specific qualifications. The imaging equipment qualification process is detailed and time-consuming, involving dose calibrator checks, special imaging camera qualifications, and dummy deliveries to ensure the entire process works smoothly before enrolling the first patient.
An often-overlooked requirement is the availability of an onsite Radiation Safety Officer (RSO). This individual plays a crucial role in maintaining compliance, implementing radiation monitoring protocols, and serving as the expert resource for all radiation safety questions. Sites without dedicated RSO support will struggle to meet the operational demands of radiopharmaceutical trials.
Operational and Personnel Readiness
The pharmacy team requires specialized capacity and training to receive, verify, and store radiopharmaceuticals. Unlike traditional investigational products that can be stored for extended periods, radiopharmaceuticals arrive on a precise schedule tied to each patient’s dosing appointment. Pharmacy staff must be available to receive shipments, often with very specific time windows, and must be trained in handling radioactive materials with appropriate shielding and safety precautions.
Scheduling flexibility is paramount. Some of the radiopharmaceuticals have limited total availability and required ordering a month or more in advance. This presents challenges with scheduling new patients, whose future treatment schedules do not have available activity due to an overlap with patients still receiving treatment. Additionally, the just-in-time nature of radiopharmaceutical delivery means that patient appointments cannot easily be rescheduled. If a patient cancels or doesn’t show up, the dose, which may have cost tens of thousands of dollars, goes to waste. Sites need robust scheduling systems and strong patient engagement protocols to minimize no-shows.
Recent radiopharmaceutical approvals, such as Pluvicto for prostate cancer, have significantly impacted the availability of nuclear medicine resources for clinical trials. Sites may find their nuclear medicine departments stretched thin, with competing demands from approved therapies and research protocols. Early conversations with nuclear medicine leadership about resource allocation are essential.
Personnel training extends beyond pharmacy and nuclear medicine. Oncologists must be appropriately credentialed and trained on protocol-specific procedures. Staff need standard operating procedures for patient preparation, infusion, monitoring, and post-treatment care. Protocols should clearly define radiation exposure monitoring for both patients and staff, including post-treatment contact restrictions and the use of safety signage.
Operational Alignment
One of the most important lessons from early radiopharmaceutical trials is that communication failures cause significant problems. Nuclear medicine teams, pharmacy staff, radiation safety officers, and oncology teams must have a shared understanding of responsibilities and workflows. These departments often operate in silos in traditional practice, but radiopharmaceutical trials require unprecedented coordination.
Sites should establish clear communication pathways and escalation lines before enrolling the first patient. Regular cross-functional meetings during study startup can identify potential disconnects. For example, nuclear medicine staff may not realize that patients must provide informed consent before receiving any study procedures, or oncology staff may not understand the specific shielding requirements for radiopharmaceutical administration.
The lack of familiarity with clinical research standards in nuclear medicine departments poses a particular challenge. Data collection practices that would be standard in nuclear medicine, such as recording imaging calculations in Excel spreadsheets, are unacceptable in clinical trials, where all data must be captured in a validated electronic data capture system with a clear audit trail. Sites must invest in training and quality control processes to ensure source data verification can be completed successfully.
Patient Journey Considerations
The patient experience in radiopharmaceutical trials differs significantly from traditional oncology studies. Treatment protocols often include a screening dose to determine eligibility or understand disease burden, followed by treatment doses every four to six weeks. This creates a substantial travel burden for patients, who may need to visit the site frequently for time-sensitive imaging and assessments.
Sites should consider offering concierge services to coordinate travel and provide subsistence allowances. Patient navigators or nurse coordinators can provide personalized support, address concerns about radiation exposure, and help patients understand the complex treatment schedule. Clear education materials, including visual aids to explain radiopharmaceutical concepts, improve patient understanding and engagement.
Radiation anxiety is real for many patients and families. Pre-study counseling that sets realistic expectations and addresses specific concerns helps with enrollment and retention. Some protocols include mandatory biopsies, which can be a significant barrier to enrollment. Understanding these challenges and having strategies to address them improves patient recruitment and retention.
Safety Oversight and Data Integrity
Radiopharmaceutical interventional treatment trials require robust safety management plans that address both clinical toxicity and radiation safety. Early detection algorithms for monitoring trends in adverse events, particularly gastrointestinal toxicities, help identify problems before they become serious. Sites need established baseline and ongoing laboratory panels with predefined triggers for escalation.
Adverse event grading and reporting require specific training. Staff must use CTCAE version 5.0 criteria with particular attention to radiation-related toxicities. Serious adverse event reporting must align with ICH-GCP timelines and clearly distinguish radiation-related adverse effects from other types of adverse events. Radiation exposure logs must be maintained for any staff or patient incidents.
Quality control and source data reviews are essential for data integrity. Well counter calibration and maintenance vary across sites, with different facilities using different methods and equipment. Standardized processes across all sites are highly recommended to ensure data comparability and quality.
Logistics and Supply Chain Management
The just-in-time nature of radiopharmaceutical delivery requires dedicated logistics coordination. A specialized logistics coordinator should work closely with the CDMO to manage patient visit schedules and coordinate investigational medicinal product supply. This individual serves as the central interface between the sponsor, CDMO, and clinical sites.
Close collaboration with CDMOs experienced in radioactive material handling ensures compliant, secure, and traceable shipments with 24/7 tracking and contingency protocols. The logistics coordinator must maintain a detailed schedule tracking each patient’s dosing timeline and align deliveries accordingly. Sites must provide forecasts of patient recruitment to enable just-in-time shipment of diagnostic and therapeutic doses while minimizing waste from cancellations or no-shows.
Timeline Considerations
Site activation for radiopharmaceutical trials takes significantly longer than traditional oncology studies. The process includes CDMO engagement, equipment calibrations, scanner qualifications, regulatory document preparation, laboratory and pharmacy manual development, and test shipments. Sites should expect the qualification process to extend several months beyond traditional study startup timelines.
Early engagement is critical. Sites interested in participating in radiopharmaceutical trials should begin conversations with sponsors during protocol development, not after the protocol is finalized. This allows adequate time for licensing amendments, infrastructure assessment and upgrades, equipment qualification, and staff training.
Conclusion
Participating in radiopharmaceutical trials represents a significant commitment for clinical sites, requiring investments in infrastructure, specialized training, regulatory compliance, and cross-functional coordination that go well beyond traditional oncology studies. However, these trials also represent the cutting edge of precision oncology, offering sites the opportunity to be at the forefront of therapeutic innovation.
Sites that successfully prepare for radiopharmaceutical trials position themselves as preferred partners for this growing segment of clinical research. The key to success lies in early preparation, honest assessment of capabilities and gaps, investment in infrastructure and training, and a commitment to cross-functional communication and coordination. With proper preparation, clinical sites can safely and effectively participate in studies that may transform cancer treatment for patients worldwide.
About TD2 Oncology
TD2 Oncology is a specialized oncology-focused contract research organization (CRO) offering integrated preclinical, regulatory, and clinical services for complex cancer drug development. With deep expertise in targeted therapies, like radiopharmaceuticals, we support sponsors and sites throughout the full development lifecycle.
For RLT clinical trials, TD2 Oncology works directly with research sites to help them prepare for the unique operational, regulatory, and infrastructure demands of these complex trials. Our team provides guidance on isotope licensing requirements, nuclear medicine and pharmacy readiness, imaging qualification, workflow development, radiation safety compliance, and just-in-time product logistics. We share real-world best practices, help sites anticipate common activation barriers, and offer practical support to ensure teams, systems, and facilities are ready before trial launch. Whether a site is entering the radiopharmaceutical space for the first time or expanding existing capabilities, TD2 Oncology serves as a collaborative partner to streamline activation and strengthen long-term readiness for future RLT studies.
About the Authors
Jenny Keppler, MBA, Vice President, Translational Medicine, has more than 20 years of experience in translational research, clinical trials and regulatory strategy across academic, industry and CRO settings. Over the course of her career, she has overseen investigational new drug (IND) filings from phase I through phase II for both small and large molecules.
Theresa Bruce, President, Clinical Operations, is an experienced clinical operations executive with over 25 years of oncology CRO, drug development and leadership expertise, including COO of Nexus Oncology; and EVP Global Clinical Operations at Ockham.
