Gravity versus pump-driven infusion in targeted radionuclide therapy: a model-based dosimetric evaluation of extravasation.

Abstract

Background: Intravenous administration of [Formula: see text]Lu-labeled radiopharmaceuticals (RPMs) such as PSMA and DOTATATE entails a risk of extravasation, potentially resulting in absorbed doses exceeding thresholds for deterministic tissue damage. Gravity-driven and pump-assisted infusion methods differ in dilution and flow dynamics, which directly affect the extravasated dose. This study aimed to extend and validate an analytical model for quantitative comparison of extravasation-related dosimetric risks between both strategies and to inform clinical protocol optimization.

Methods: A previously published analytical model for gravity-driven delivery was extended to pump-assisted infusion by incorporating method-specific dilution kinetics within the mixing compartment and laminar (Poiseuille) flow through the infusion line and venous system. Extravasation was modeled mechanistically to estimate extravasated activity, concentration, and equivalent dose rate (EDR) at the injection site. Model validation was performed by comparing simulated EDRs with in vivo measurements from 28 clinical [Formula: see text]Lu-PSMA infusions using the ED3 bilateral dosimetry system. Simulations covered clinically relevant parameter ranges, and absorbed doses were derived by combining simulated concentrations with Monte Carlo-based S-values, assuming an effective residence time of 1.5 h supported by clinical SPECT/CT data.

Results: The model reproduced measured EDR kinetics with a mean deviation of 16 % during infusion. Gravity-driven infusions generated steep concentration peaks in case of early extravasation, with absorbed dose strongly dependent on onset timing. Pump-assisted delivery yielded stable profiles largely independent of onset. Across clinical parameter ranges, gravity-based protocols produced extravasated concentrations of 155-345 [Formula: see text] and doses of 30-68 Gy, with mitigation relying on vial pre-dilution at the cost of prolonged infusion times. Pump-assisted protocols allowed safer modulation (21-180 [Formula: see text], 4-35 Gy) through independent control of RPM and saline flow rates, without vial dilution. For equivalent infusion durations (e.g., 44 min), pump delivery achieved extravasated doses and concentrations about sevenfold lower than gravity (5.2 vs. 35 Gy), supporting its clinical value for protocol optimization and radioprotection.

Conclusion: We present an analytical model for estimating absorbed dose in the event of extravasation during [Formula: see text]Lu-RPM infusion. The results highlight the decisive safety benefits of pump-assisted administration over gravity-driven delivery and support its implementation as a proactive strategy to minimize extravasation risk, improve patient safety, and harmonize therapeutic protocols across centres .