177Lu-PSMA dosimetry made easy: from theory to practical implementation.

177Lu-PSMA-targeted radioligand therapy (TRT) represents a major advance in managing metastatic castration-resistant prostate cancer (mCRPC), exploiting PSMA overexpression to deliver β-particle radiation precisely to tumor cells while sparing healthy tissue. Following demonstration of survival and quality-of-life benefits in the Phase III VISION trial, it has been approved by the FDA and incorporated into international guidelines as a standard-of-care option. As clinical use expands, patient-specific internal dosimetry is increasingly recognized as essential for optimizing efficacy, minimizing toxicity, and enabling personalized treatment planning. This review provides a practical, step-by-step framework for performing 177Lu-PSMA dosimetry, from administration and quantitative imaging to time-activity-curve generation and absorbed-dose estimation. Evidence supports a strong correlation between tumor absorbed dose and therapeutic response, while established thresholds for organs at risk, particularly kidneys, salivary glands, and bone marrow, help guide safe administration. Although logistical barriers have limited routine implementation, innovations such as reduced-field-of-view imaging, deep-learning-assisted reconstruction, simplified single- or dual-time-point schemes, and automated pipelines are streamlining workflows. Machine-learning dose-prediction models and ongoing prospective trials, such as PRODIGY-1, are advancing individualized dosing strategies. Personalized dosimetry is thus emerging as a cornerstone for maximizing the safety and effectiveness of 177Lu-PSMA therapy and integrating it seamlessly into routine clinical practice.