Article summary
Theranostics in Nuclear Medicine
Historical, Regulatory, and Evidence Context for the Practicing Nuclear Medicine Physician
Summary
Theranostics — the pairing of diagnostic imaging with targeted radiopharmaceutical therapy — has moved from niche nuclear medicine practice to a mainstream oncology modality in under a decade. The approvals of Lutathera (2018) and Pluvicto (2022, expanded 2025) catalyzed billions in investment and a rapid expansion of clinical trials globally.
But the field is expanding faster than its evidence, regulatory frameworks, and operational infrastructure can support. This paper, authored by Bracken’s own clinical leadership, uses 100 years of translational history to frame the current moment honestly, and to give practicing nuclear medicine physicians and industry program leaders a clear-eyed picture of what comes next.
Key points from the paper
Modern theranostics is built on a century of isotope therapyRecent approvals have shifted expectations toward registration-quality evidence and scalable delivery — but that history matters for understanding where the field is headed.
RPT trials follow conventional phase structure — with distinctive constraintsEvery radiopharmaceutical therapy trial must integrate target-confirmation imaging, CMC and supply constraints, radiation safety, and late-toxicity surveillance in ways conventional drug trials do not.
Imaging eligibility is where trials succeed or failEndpoint choice should match disease context and line of therapy — but imaging eligibility definitions and adjudication workflows are often the true rate-limiting steps for accrual.
Dosimetry is increasingly central — and increasingly expectedTrials should specify what is feasible at sites, what is centralized, standardized, and auditable. FDA’s draft guidance makes this explicit.
Readiness is people, processes, and quality systemsWorkforce training and longitudinal follow-up are as important as scanner access. Department readiness cannot be reduced to equipment.
The stakes — why this matters now
$10B+
in radiopharma acquisitions since 2017
Novartis, BMS, AZ, Eli Lilly · Table 2
58
active Lu-177 trials in 2025, up from 16 in 2015
ClinicalTrials.gov · Table 6
27×
growth in Ac-225 trials since 2015
1 trial → 27 trials · Table 6
Three critical gaps the paper identifies
1
Dosimetry is no longer optional — but it isn’t standardized
Quantitative SPECT/CT and voxel-based dosimetry methods have matured, but there is no consensus methodology across trials. FDA’s draft guidance signals that dose and schedule must be justified with exposure-response evidence — not historical convention.
Regulatory pressure increasing
2
Regulatory pathways are evolving faster than programs can adapt
Drug regulation, radiation protection, and radiopharmacy manufacturing standards are all in motion simultaneously. For alpha emitters like Ac-225, there is no established FDA approval precedent — sponsors cannot apply a Lu-177 template.
No Ac-225 FDA approvals yet
3
Operational risk is being treated as an afterthought
Isotope decay, delivery windows, radiopharmacy capacity, and site throughput are core trial design constraints — not logistics. Protocols that are scientifically attractive but operationally infeasible fail at the site level through slow accrual and protocol deviations.
Accrual bottleneck risk
What comes next
The readiness agenda
There is a practical, 3-part framework for navigating what comes next.
The authors outline a concrete readiness agenda for nuclear medicine departments, clinical trial sites, and industry programs — built from the regulatory and evidence realities documented in this review. The framework addresses the workforce, operational, and clinical trial literacy gaps that will determine which programs succeed in the next decade of theranostics.
