Extravasation of Therapeutic Radiopharmaceuticals: A Systematic Review and Management Proposal

The extravasation of therapeutic radiopharmaceuticals presents a risk of radiation-induced injury. The recent rise in the use of therapeutic radiopharmaceuticals has highlighted the need for a better understanding of the consequences of extravasation and different treatment approaches, which are summarized in this systematic review. Here, we propose a standardized, step-by-step management guide with the aim of integrating this approach into future guidelines. <b>Methods:</b> A search of MEDLINE and Embase databases was conducted. The first search string contained synonyms of <i>extravasation</i> The second search string contained the names of therapeutic radiopharmaceuticals. Case reports on extravasation of therapeutic radiopharmaceuticals were included in the analysis. Extracted data were standardized for nomenclature and absorbed dose units. Reported absorbed doses, side effects, and treatment approaches were grouped by radiopharmaceutical. Proposed management strategies were summarized chronologically by author. <b>Results:</b> After screening 3,033 abstracts, conducting a full-text review of 75 publications, and screening all references of included publications and European Association of Nuclear Medicine guidelines on therapeutic radiopharmaceuticals, 28 publications remained, involving 39 case reports of extravasation of therapeutic radiopharmaceuticals. The severity of side effects varied widely, from mild and quickly resolving to severe, depending on the radiopharmaceutical used. The most frequent acute side effects were transient swelling, pain, and redness. In cases of radiation injury, the degree of severity, ranging from erythema and dry or moist desquamation to necrosis, was related to the absorbed dose. The most frequently reported intervention after extravasation was mobilization of the affected limb, which included massage, elevation of the arm, stress ball use, or hand-pumping exercises. Management strategies to prevent extravasation focused mainly on ensuring adequate vascular access. <b>Conclusion:</b> Extravasation of therapeutic radiopharmaceuticals is a rarely reported complication, with its severity determined by the activity infiltrated, retention time, and energy of the particulate radiation. Severe radiation-induced injuries were observed after radiosynoviorthesis or extravasation of large molecules (e.g., [⁹⁰Y]Y-ibritumomab tiuxetan). To date, there have been no reported cases of radiation-induced damage after extravasation during peptide receptor radionuclide therapy or prostate-specific membrane antigen-targeted radiopharmaceutical therapy. This systematic review highlights the consequences of 39 documented cases of extravasation of therapeutic radiopharmaceuticals and offers a step-by-step management guide.