Ali Afshar-Oromieh

Zhihao Chen, Jiahui Wang, Yizhou Chen et al.

PET theranostics is transforming precision oncology, yet treatment response varies substantially; many patients receiving 177Lu-PSMA radioligand therapy (RLT) for metastatic castration-resistant prostate cancer (mCRPC) fail to respond, demanding reliable pre-therapy prediction. While LLM-based agents have shown remarkable potential in complex medical diagnosis, their application to PET theranostic outcome prediction remains unexplored, which faces three key challenges: (1) data and knowledge scarcity: RLT was only FDA-approved in 2022, yielding few training cases and insufficient domain knowledge in general LLMs; (2) heterogeneous information integration: robust prediction hinges on structured knowledge extraction from PET/CT, laboratory tests, and free-text clinical documentation; (3) evidence-grounded reasoning: clinical decisions must be anchored in trial evidence rather than LLM hallucinations. In this paper, we present TheraAgent, to our knowledge, the first agentic framework for PET theranostics, with three core innovations: (1) Multi-Expert Feature Extraction with Confidence-Weighted Consensus, where three specialized experts process heterogeneous inputs with uncertainty quantification; (2) Self-Evolving Agentic Memory (SEA-Mem), which learns prognostic patterns from accumulated cases, enabling case-based reasoning from limited data; (3) Evidence-Calibrated Reasoning, integrating a curated theranostics knowledge base to ground predictions in VISION/TheraP trial evidence. Evaluated on 35 real patients and 400 synthetic cases, TheraAgent achieves 75.7% overall accuracy on real patients and 87.0% on synthetic cases, outperforming MDAgents and MedAgent-Pro by over 20%. These results highlight a promising blueprint for trustworthy AI agents in PET theranostics, enabling trial-calibrated, multi-source decision support. Code will be released upon acceptance.

Alejandro Lopez-Montes, Robert Seifert, Astrid Delker et al.

In this work we explored the use of patient specific reinforced learning to generate 3D activity maps from two 2D planar images (anterior and posterior). The solution of this problem remains unachievable using conventional methodologies and is of particular interest for dosimetry in nuclear medicine where approaches for post-therapy distribution of radiopharmaceuticals such as 177Lu-PSMA are typically done via either expensive and long 3D SPECT acquisitions or fast, yet only 2D, planar scintigraphy. Being able to generate 3D activity maps from planar scintigraphy opens the gate for new dosimetry applications removing the need for SPECT and facilitating multi-time point dosimetry studies. Our solution comprises the generation of a patient specific dataset with possible 3D uptake maps of the radiopharmaceuticals withing the anatomy of the individual followed by an AI approach (we explored both the use of 3DUnet and diffusion models) able to generate 3D activity maps from 2D planar images. We have validated our method both in simulation and real planar acquisitions. We observed enhanced results using patient specific reinforcement learning (~20% reduction on MAE and ~5% increase in SSIM) and better organ delineation and patient anatomy especially when combining diffusion models with patient specific training yielding a SSIM=0.89 compared to the ground truth for simulations and 0.73 when compared to a SPECT acquisition performed half an hour after the planar. We believe that our methodology can set a change of paradigm for nuclear medicine dosimetry allowing for 3D quantification using only planar scintigraphy without the need of expensive and time-consuming SPECT leveraging the pre-therapy information of the patients.

Alejandro Lopez-Montes, Fereshteh Yousefirizi, Yizhou Chen et al.

KEY WORDS: Artificial Intelligence (AI), Theranostics, Dosimetry, Radiopharmaceutical Therapy (RPT), Patient-friendly dosimetry KEY POINTS - The rapid evolution of radiopharmaceutical therapy (RPT) highlights the growing need for personalized and patient-centered dosimetry. - Artificial Intelligence (AI) offers solutions to the key limitations in current dosimetry calculations. - The main advances on AI for simplified dosimetry toward patient-friendly RPT are reviewed. - Future directions on the role of AI in RPT dosimetry are discussed.