DOI: 10.3390/jcm15166339 ISSN: 2077-0383

Theranostics in Radiation Medicine: Integrating Radiopharmaceutical Therapy and External-Beam Radiotherapy

Senthamizhchelvan Srinivasan, Joseph A. Moore, Sarah Han-Oh

Theranostics has transformed nuclear medicine from an imaging-focused discipline into a data-rich radiation medicine platform in which target expression, pharmacokinetics, tumor dose, and response can be measured in the same patient. This critical narrative review evaluates patient-specific integration of radiopharmaceutical therapy (RPT) with external-beam radiotherapy (EBRT), with emphasis on quantitative imaging, absorbed-dose estimation, spatial registration, biological interpretation, adaptation thresholds, and reporting. We performed a targeted search of PubMed/MEDLINE, ClinicalTrials.gov, U.S. Food and Drug Administration records, professional-society guidance, and reference lists for English-language evidence available through 31 July 2026, prioritizing guidelines, regulatory documents, randomized and prospective trials, technical validation studies, and clinically informative retrospective series. Established RPT platforms are distinguished from investigational combined-modality applications and emerging or speculative technologies. Liver-directed Y-90 radioembolization combined with focal EBRT remains the most developed model, whereas head and neck, prostate, meningioma, lymphoma, and bone-dominant strategies illustrate distinct clinical geometries and levels of readiness. Across platforms, direct addition of absorbed dose in gray (Gy) is a geometric description, not automatically a biological endpoint; biologically effective dose (BED) and equivalent dose in 2-Gy fractions (EQD2) should be treated as model-based estimates with explicit assumptions. Future theranostic radiation medicine should therefore be built on prospective trials with prespecified dosimetry, uncertainty analysis, adaptation rules, and shared cross-modality reporting standards.

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