{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:14:47Z","timestamp":1784556887053,"version":"3.55.0"},"reference-count":19,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE has become a cornerstone in the management of neuroendocrine tumors (NETs). However, the efficiency of this targeted therapy is highly dependent on the radiopharmaceutical drug delivery system and its infusion kinetics, which influence systemic biodistribution and therapeutic efficacy. This study evaluates various gravity-based infusion fluid dynamics to optimize the drug delivery profile, ensuring standardized delivery while minimizing residual activity. Methods: A retrospective analysis of 127 administrations of 177Lu-DOTATATE (7.4 GBq per cycle) was conducted across 35 patients with NETs to assess vial dilution kinetics. Four distinct infusion rate (IR) strategies were compared to evaluate mass balance and delivery efficiency: constant infusion rate (1-IR); a single rate increase at 10 min (2-IR); two rate increases at 10 and 30 min (3-IR); and three rate increases at 10, 30, and 40 min (4-IR). Results: Stepwise increases in the IR significantly accelerated the vial clearance kinetics and reduced radiopharmaceutical stagnation within the infusion lines. Successful delivery of the target dose (98% of the pre-infusion activity measured in each specific vial) was achieved in 56% of cases with the 1-IR protocol (9 injections) and increased to 87% with 2-IR (45 injections), 97% with 3-IR (60 injections), and 100% with 4-IR (13 injections). Conclusions: Modulating fluid dynamics through stepwise IR protocols significantly enhances radiopharmaceutical delivery efficiency. The 3-IR protocol offers a favorable balance between procedural efficiency and clinical safety.<\/jats:p>","DOI":"10.3390\/pharmaceutics18070889","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:18:31Z","timestamp":1784553511000},"page":"889","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optimization of Gravity Infusion Protocols for 177Lu-DOTATATE Administration in Peptide Receptor Radionuclide Therapy"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2703-4142","authenticated-orcid":false,"given":"Salvatore","family":"Grasso","sequence":"first","affiliation":[{"name":"Unit of Medical Physics and Radioprotection, University Hospital Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Varallo","sequence":"additional","affiliation":[{"name":"Unit of Medical Physics and Radioprotection, University Hospital Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0560-2997","authenticated-orcid":false,"given":"Valeria","family":"Gaudieri","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9505-7306","authenticated-orcid":false,"given":"Michele","family":"Klain","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Pastore","sequence":"additional","affiliation":[{"name":"Unit of Medical Physics and Radioprotection, University Hospital Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0414-1474","authenticated-orcid":false,"given":"Stefania","family":"Arena","sequence":"additional","affiliation":[{"name":"Department of Mental and Physical Health and Preventive Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Oliviero","sequence":"additional","affiliation":[{"name":"Unit of Medical Physics and Radioprotection, University Hospital Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1712-5849","authenticated-orcid":false,"given":"Mauro","family":"Buono","sequence":"additional","affiliation":[{"name":"Unit of Medical Physics and Radioprotection, University Hospital Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Manzi","sequence":"additional","affiliation":[{"name":"Unit of Medical Physics and Radioprotection, University Hospital Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Schiano","sequence":"additional","affiliation":[{"name":"Unit of Medical Physics and Radioprotection, University Hospital Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"Nappi","sequence":"additional","affiliation":[{"name":"IRCCS SYNLAB-SDN, 80143 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Totaro","sequence":"additional","affiliation":[{"name":"Unit of Nuclear Medicine, University Hospital Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario Raffaele","family":"Bonifacio","sequence":"additional","affiliation":[{"name":"Unit of Nuclear Medicine, University Hospital Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3431-7658","authenticated-orcid":false,"given":"Alberto","family":"Cuocolo","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy"},{"name":"IRCCS SYNLAB-SDN, 80143 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Clemente","sequence":"additional","affiliation":[{"name":"Unit of Medical Physics and Radioprotection, University Hospital Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.annonc.2020.03.304","article-title":"Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"31","author":"Pavel","year":"2020","journal-title":"Ann. 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