[177Lu]Lu-PSMA extravasation: from quantitative imaging to clinical guidelines

Objective.Extravasation of therapeutic radioligands such as [177Lu]Lu-PSMA-617 or [177Lu]Lu-DOTATATE is rare but may result in localized radiation injury. In the absence of standardized guidelines, management remains empirical. We describe two cases of [177Lu]Lu-PSMA extravasation, evaluated using a fully automated, time-resolved dosimetric workflow supporting evidence-based conservative management.Approach.Two patients exhibiting localized extravasation were treated using conservative measures, including manual massage, warmth application, and arm elevation. Clearance kinetics were assessed using quantitative SPECT/CT, comprising 3-4 early acquisitions within 6 h, followed by imaging at 24 h and >48 h. Absorbed doses were calculated within threshold-based sub-volumes (ranging from <1 ml to the full volume) using mono-exponential fitting. Systemic dosimetry of organs at risk and metabolic tumor volume (MTV) was assessed in both patients and, for one patient, compared across extravasated and uneventful cycles. The analytical pipeline incorporated deep learning-based CT segmentation, anatomy-guided partial volume correction, Monte Carlo-derived dose computation, and compartment-specific kinetic modeling.Main results.Both patients demonstrated rapid clearance of extravasated activity, with effective half-lives of 1.42 h and 1.52 h. Even the most highly irradiated sub-volumes (<1 ml) received <10 Gy, far below necrosis thresholds. During extravasated cycles, renal absorbed doses exceeded 1 Gy, while MTV doses reached 32.1 Gy and 9.6 Gy, respectively. In Patient 1, systemic dosimetry was nearly identical between extravasated and subsequent cycles (<10% variation for kidneys). The only substantial change was a decline in MTV dose (32.1 → 20.2 Gy), consistent with declining tumor uptake over successive [177Lu]Lu-PSMA administrations.Significance.[177Lu]Lu-PSMA extravasation undergoes rapid clearance under conservative management, with absorbed doses below deterministic thresholds and unaffected systemic biodistribution. Conservative interventions-massage, warming, and arm elevation are therefore justified. Automated quantitative dosimetry enables same-day dose estimation, providing an objective basis for timely clinical decision-making and paving the way toward standardized management protocols.