Radioligand therapies (RLTs) are rapidly moving from experimental programs into standard of care, reshaping how clinical trials are designed, operationalized, and scaled globally. Discussions during a pre-conference workshop at the November Society of Nuclear Medicine and Molecular Imaging (SNMMI) meeting highlighted a consistent theme. Scientific innovation is advancing faster than the operational infrastructure required to support it. Closing that gap will be essential for sponsors seeking to deliver RLT programs efficiently, compliantly, and at scale.

Across site operations, qualification, study design, and industry collaboration, workshop participants surfaced practical challenges along with opportunities to rethink how radiopharmaceutical trials are executed.

Site Operations: Communication, Continuity, and Accountability

One of the most persistent site level challenges discussed at SNMMI was communication between clinical research teams and nuclear medicine departments. While nuclear medicine is central to RLT delivery, research coordinators are not always equipped to speak the same technical language. This disconnect can create friction in scheduling, protocol interpretation, and day-to-day execution.

High turnover at clinical research organizations (CROs) further complicates site operations. Sites cited frequent changes in operational contacts as a major source of frustration, particularly in trials that require specialized nuclear medicine expertise. Loss of continuity can slow issue resolution, increase training burden, and erode site confidence over time.

Operational complexity increases further when radiotracers must be labeled at the site. Workshop discussions highlighted the value of separating clinical and manufacturing Clinical Trial Agreements (CTAs). Manufacturing contracts can often be executed more quickly, enabling technology transfer and preparation to proceed while the clinical CTA remains under negotiation. This sequencing can help sponsors avoid downstream delays during site activation.

Participants also raised difficult but necessary questions around patient death shortly after receiving RLT. These included how radioactive bodies are stored until decay occurs and the reluctance of funeral homes to accept them. Such scenarios underscore the importance of proactive planning, clear site guidance, and alignment with local regulations well before first patient in.

Site Qualification: The Case for Standardization

Site qualification remains a major bottleneck for radiopharmaceutical trials. Workshop attendees noted that some sites are unable to perform phantom scans outside of standard operating hours, limiting flexibility and slowing activation timelines.

More broadly, there was strong consensus around the need for standardized site qualification forms and processes. Today, sponsors often require sites to repeatedly qualify scanners for each new study, even when the same equipment and isotope are used. Confidentiality constraints prevent reuse of prior qualification data, resulting in inefficiency for both sponsors and sites.

Participants emphasized that all scanners that could potentially be used on a study must be qualified, adding further complexity. Standardized qualification by isotope, combined with certification from a neutral organization like SNMMI that could be reused across studies, was identified as a meaningful opportunity to reduce redundancy and accelerate startup.

There was also discussion about synchronized clocks for pharmacokinetic sampling. While this may appear to be a minor operational detail, given the rapid time points, inconsistent timing can materially affect data integrity in dosimetry-driven trials.

SNMMI was encouraged to take a leadership role in establishing these standards, reflecting broad recognition that scalable solutions will require collaboration across the nuclear medicine community.

Study Design in a Shifting Treatment Landscape

As RLTs transition into standard of care, longstanding study design assumptions are being challenged. Not all imaging scanners operate with the same scan times, a factor that must be carefully considered when defining dosimetry time points.

Even more consequential is the impact of RLT becoming standard of care on randomized Phase III trials. Workshop discussions raised concerns about how comparator arms will be implemented and whether limitations in site capabilities could restrict where studies can be conducted. In some cases, these constraints may limit geographic reach or reduce the pool of eligible sites.

These realities reinforce the importance of aligning protocol design with real world site capabilities early in development, before operational constraints compromise enrollment, execution, or data quality.

Industry and Society Collaboration as a Lever for Scale

Encouragingly, the workshop highlighted several collaborative efforts already underway. The formation of the Nuclear Medicine Trials Group, along with its role in validating scanners and gamma counters, represents an important step toward greater consistency across trials.

Industry also has a role to play. Investments in equipment were discussed as a way sponsors can directly enable site readiness, while large-scale facilities that support radiopharmaceutical manufacturing demonstrate how infrastructure investment can expand trial capacity.

From a therapeutic perspective, discussions also touched on the balance between tumor penetration and liver or kidney accumulation, the influence of molecular size, and open questions such as whether fewer, higher doses may be optimal for agents like 177LuPSMA. These scientific considerations further emphasize the need for operational models that can evolve alongside emerging evidence.

Turning Insight into Execution

Taken together, SNMMI discussions point to a clear conclusion. The future success of RLT programs will depend as much on operational excellence as on scientific innovation. Standardized qualification, stronger site and CRO continuity, proactive planning for complex scenarios, and collaboration across industry and professional societies are no longer optional. They are prerequisites for scale.

For sponsors navigating this landscape, the opportunity lies in translating these insights into integrated trial strategies that align protocol design, site readiness, and operational execution from the outset. As radioligand therapies continue to expand across indications and geographies, building that foundation early will be critical to advancing both scientific progress and patient impact.

For additional reading, explore our insight brief, Optimizing Doses for Combination Therapies in Oncology: Integrating best practices and regulatory expectations to streamline development.