Radiotheranostics refers to the pairing of radioactive imaging biomarkers with radioactive therapeutic compounds that deliver ionizing radiation. Given the introduction of very promising radiopharmaceuticals, the radiotheranostics approach is creating a novel paradigm in personalized, targeted radionuclide therapies (TRTs), also known as radiopharmaceuticals (RPTs). Radiotherapeutic pairs targeting somatostatin receptors (SSTR) and prostate-specific membrane antigens (PSMA) are increasingly being used to diagnose and treat patients with metastatic neuroendocrine tumors (NETs) and prostate cancer. In parallel, radiomics and artificial intelligence (AI), as important areas in quantitative image analysis, are paving the way for significantly enhanced workflows in diagnostic and theranostic fields, from data and image processing to clinical decision support, improving patient selection, personalized treatment strategies, response prediction, and prognostication. Furthermore, AI has the potential for tremendous effectiveness in patient dosimetry which copes with complex and time-consuming tasks in the RPT workflow. The present work provides a comprehensive overview of radiomics and AI application in radiotheranostics, focusing on pairs of SSTR- or PSMA-targeting radioligands, describing the fundamental concepts and specific imaging/treatment features. Our review includes ligands radiolabeled by ⁶⁸Ga, 18F, ¹⁷⁷Lu, ⁶⁴Cu, ⁹⁰Y, and 225Ac. Specifically, contributions via radiomics and AI towards improved image acquisition, reconstruction, treatment response, segmentation, restaging, lesion classification, dose prediction, and estimation as well as ongoing developments and future directions are discussed.

Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is revolutionizing the treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) patients. This study aimed to establish patient-specific radiation dosimetry for [¹⁷⁷Lu]Lu-PSMA-617 RLT in Iranian patients with mCRPC. Twelve biopsy-proven prostate cancer patients (aged 68.73 ± 5.26 yr) underwent 6.62 ± 0.36 GBq [¹⁷⁷Lu]Lu-PSMA-617 RLT. Post-therapy whole-body planar scans were acquired approximately at 4, 48, and 72 h post-administration, alongside a single SPECT/CT around 48 h using Siemens Symbia T₂ to obtain cumulated activity. An imaging protocol and dosimetry approach were designed to balance between time efficacy and accuracy in post-therapeutic dosimetry. Using accurate activity calibration, S-values were calculated by importing SPECT/CT images as the source/geometry into the Geant4 application for the tomographic emission (GATE) Monte Carlo (MC) toolkit. The Medical Internal Radiation Dose (MIRD) scheme was followed for subsequent absorbed dose (AD) calculations in organs at risk (OAR) and tumoral lesions using the dose actor and accumulated activities for precise dose estimations. Using the MC approach, the mean ADs to the liver, spleen, right and left kidneys, and tumor lesions were 0.11 ± 0.04 Gy/GBq, 0.08 ± 0.03 Gy/GBq, 0.34 ± 0.09 Gy/GBq, 0.34 ± 0.10 Gy/GBq, and 0.83 ± 0.54 Gy/GBq, respectively. Notably, tumoral lesions demonstrated significantly higher ADs, indicating enhanced uptake of radiopharmaceuticals by malignant cells. This study indicates that the ADs of OARs and tumoral lesions from [¹⁷⁷Lu]Lu-PSMA-617 RLT in patients with mCRPC are consistent with existing literature. The dosimetry findings suggest that increasing the administered activity of [¹⁷⁷Lu]Lu-PSMA-617 RLT is feasible and does not pose a significant risk of adverse effects on OARs, as supported by our data. However, to validate the safety and efficacy of higher doses, further clinical follow-up studies are recommended.

Radiotheranostics refers to pairing of radioactive imaging biomarkers with radioactive therapeutic compounds that deliver ionizing radiation. Given the introduction of very promising radio-pharmaceuticals, the radiotheranostics approach is creating a novel paradigm in personalized, targeted radionuclide therapies (TRTs), also known as radiopharmaceuticals (RPTs). Radiother-apeutic pairs targeting somatostatin receptors (SSTR) and prostate-specific membrane antigens (PSMA) are increasingly used to diagnose and treat patients with metastatic neuroendocrine tumors (NETs) and prostate cancer. In parallel, radiomics and artificial intelligence (AI) as important areas in quantitative image analysis are paving the way for significantly enhanced workflows in diagnostic and theranostic fields, from data and image processing to clinical decision support, improving patient selection, personalized treatment strategies, response prediction, and prognostication. Furthermore, AI has the potential for tremendous effectiveness in patient dosimetry which copes with complex and time-consuming tasks in the RPT workflow. The present work provides a comprehensive overview of radiomics and AI application in radio-theranostics, focusing on pairs of SSTR- or PSMA‑targeting radioligands, describing the funda-mental concepts and specific imaging/treatment features. Our review includes ligands radio-labeled by 68Ga, 18F, 177Lu, 64Cu, 90Y, and 225Ac. Specifically, contributions by radiomics and AI towards improved image acquisition, reconstruction, treatment response, segmentation, restag-ing, lesion classification, dose prediction, and estimation as well as ongoing developments and future directions are discussed.